Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer.

PubMed

De Leersnyder, F; Vanhoorne, V; Bekaert, H; Vercruysse, J; Ghijs, M; Bostijn, N; Verstraeten, M; Cappuyns, P; Van Assche, I; Vander Heyden, Y; Ziemons, E; Remon, J P; Nopens, I; Vervaet, C; De Beer, T

2018-03-30

Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and, hence, a cost-effective practical implementation. Therefore, the aim of the current study is to increase understanding of the drying kinetics and the breakage and attrition phenomena during fluid bed drying after continuous twin screw granulation. Experiments were performed on a continuous manufacturing line consisting of a twin-screw granulator, a six-segmented fluid bed dryer, a mill, a lubricant blender and a tablet press. Granulation parameters were fixed in order to only examine the effect of drying parameters (filling time, drying time, air flow, drying air temperature) on the size distribution and moisture content of granules (both of the entire granulate and of size fractions). The wet granules were transferred either gravimetrically or pneumatically from the granulator exit to the fluid bed dryer. After a certain drying time, the moisture content reached an equilibrium. This drying time was found to depend on the applied airflow, drying air temperature and filling time. The moisture content of the granules decreased with an increasing drying time, airflow and drying temperature. Although smaller granules dried faster, the multimodal particle size distribution of the granules did not compromise uniform drying of the granules when the target moisture content was achieved. Extensive breakage of granules was observed during drying. Especially wet granules were prone to breakage and attrition during pneumatic transport, either in the wet transfer line or in the dry transfer line. Breakage and attrition of granules during transport and drying should be anticipated early on during process and formulation development by performing integrated experiments on the granulator, dryer and mill. Copyright © 2018 Elsevier B.V. All rights reserved.

Two-compartmental population balance modeling of a pulsed spray fluidized bed granulation based on computational fluid dynamics (CFD) analysis.

PubMed

Liu, Huolong; Li, Mingzhong

2014-11-20

In this work a two-compartmental population balance model (TCPBM) was proposed to model a pulsed top-spray fluidized bed granulation. The proposed TCPBM considered the spatially heterogeneous granulation mechanisms of the granule growth by dividing the granulator into two perfectly mixed zones of the wetting compartment and drying compartment, in which the aggregation mechanism was assumed in the wetting compartment and the breakage mechanism was considered in the drying compartment. The sizes of the wetting and drying compartments were constant in the TCPBM, in which 30% of the bed was the wetting compartment and 70% of the bed was the drying compartment. The exchange rate of particles between the wetting and drying compartments was determined by the details of the flow properties and distribution of particles predicted by the computational fluid dynamics (CFD) simulation. The experimental validation has shown that the proposed TCPBM can predict evolution of the granule size and distribution within the granulator under different binder spray operating conditions accurately. Copyright © 2014 Elsevier B.V. All rights reserved.

Mechanistic modelling of fluidized bed drying processes of wet porous granules: a review.

PubMed

Mortier, Séverine Thérèse F C; De Beer, Thomas; Gernaey, Krist V; Remon, Jean Paul; Vervaet, Chris; Nopens, Ingmar

2011-10-01

Fluidized bed dryers are frequently used in industrial applications and also in the pharmaceutical industry. The general incentives to develop mechanistic models for pharmaceutical processes are listed, and our vision on how this can particularly be done for fluidized bed drying processes of wet granules is given. This review provides a basis for future mechanistic model development for the drying process of wet granules in pharmaceutical processes. It is intended for a broad audience with a varying level of knowledge on pharmaceutical processes and mathematical modelling. Mathematical models are powerful tools to gain process insight and eventually develop well-controlled processes. The level of detail embedded in such a model depends on the goal of the model. Several models have therefore been proposed in the literature and are reviewed here. The drying behaviour of one single granule, a porous particle, can be described using the continuum approach, the pore network modelling method and the shrinkage of the diameter of the wet core approach. As several granules dry at a drying rate dependent on the gas temperature, gas velocity, porosity, etc., the moisture content of a batch of granules will reside in a certain interval. Population Balance Model (ling) (PBM) offers a tool to describe the distribution of particle properties which can be of interest for the application. PBM formulation and solution methods are therefore reviewed. In a fluidized bed, the granules show a fluidization pattern depending on the geometry of the gas inlet, the gas velocity, characteristics of the particles, the dryer design, etc. Computational Fluid Dynamics (CFD) allows to model this behaviour. Moreover, turbulence can be modelled using several approaches: Reynolds-averaged Navier-Stokes Equations (RANS) or Large Eddy Simulation (LES). Another important aspect of CFD is the choice between the Eulerian-Lagrangian and the Eulerian-Eulerian approach. Finally, the PBM and CFD frameworks can be integrated, to describe the evolution of the moisture content of granules during fluidized bed drying. Copyright © 2011 Elsevier B.V. All rights reserved.

Audible acoustics in high-shear wet granulation: application of frequency filtering.

PubMed

Hansuld, Erin M; Briens, Lauren; McCann, Joe A B; Sayani, Amyn

2009-08-13

Previous work has shown analysis of audible acoustic emissions from high-shear wet granulation has potential as a technique for end-point detection. In this research, audible acoustic emissions (AEs) from three different formulations were studied to further develop this technique as a process analytical technology. Condenser microphones were attached to three different locations on a PMA-10 high-shear granulator (air exhaust, bowl and motor) to target different sound sources. Size, flowability and tablet break load data was collected to support formulator end-point ranges and interpretation of AE analysis. Each formulation had a unique total power spectral density (PSD) profile that was sensitive to granule formation and end-point. Analyzing total PSD in 10 Hz segments identified profiles with reduced run variability and distinct maxima and minima suitable for routine granulation monitoring and end-point control. A partial least squares discriminant analysis method was developed to automate selection of key 10 Hz frequency groups using variable importance to projection. The results support use of frequency refinement as a way forward in the development of acoustic emission analysis for granulation monitoring and end-point control.

The combined effect of wet granulation process parameters and dried granule moisture content on tablet quality attributes.

PubMed

Gabbott, Ian P; Al Husban, Farhan; Reynolds, Gavin K

2016-09-01

A pharmaceutical compound was used to study the effect of batch wet granulation process parameters in combination with the residual moisture content remaining after drying on granule and tablet quality attributes. The effect of three batch wet granulation process parameters was evaluated using a multivariate experimental design, with a novel constrained design space. Batches were characterised for moisture content, granule density, crushing strength, porosity, disintegration time and dissolution. Mechanisms of the effect of the process parameters on the granule and tablet quality attributes are proposed. Water quantity added during granulation showed a significant effect on granule density and tablet dissolution rate. Mixing time showed a significant effect on tablet crushing strength, and mixing speed showed a significant effect on the distribution of tablet crushing strengths obtained. The residual moisture content remaining after granule drying showed a significant effect on tablet crushing strength. The effect of moisture on tablet tensile strength has been reported before, but not in combination with granulation parameters and granule properties, and the impact on tablet dissolution was not assessed. Correlations between the energy input during granulation, the density of granules produced, and the quality attributes of the final tablets were also identified. Understanding the impact of the granulation and drying process parameters on granule and tablet properties provides a basis for process optimisation and scaling. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimization of critical quality attributes in continuous twin-screw wet granulation via design space validated with pilot scale experimental data.

PubMed

Liu, Huolong; Galbraith, S C; Ricart, Brendon; Stanton, Courtney; Smith-Goettler, Brandye; Verdi, Luke; O'Connor, Thomas; Lee, Sau; Yoon, Seongkyu

2017-06-15

In this study, the influence of key process variables (screw speed, throughput and liquid to solid (L/S) ratio) of a continuous twin screw wet granulation (TSWG) was investigated using a central composite face-centered (CCF) experimental design method. Regression models were developed to predict the process responses (motor torque, granule residence time), granule properties (size distribution, volume average diameter, yield, relative width, flowability) and tablet properties (tensile strength). The effects of the three key process variables were analyzed via contour and interaction plots. The experimental results have demonstrated that all the process responses, granule properties and tablet properties are influenced by changing the screw speed, throughput and L/S ratio. The TSWG process was optimized to produce granules with specific volume average diameter of 150μm and the yield of 95% based on the developed regression models. A design space (DS) was built based on volume average granule diameter between 90 and 200μm and the granule yield larger than 75% with a failure probability analysis using Monte Carlo simulations. Validation experiments successfully validated the robustness and accuracy of the DS generated using the CCF experimental design in optimizing a continuous TSWG process. Copyright © 2017 Elsevier B.V. All rights reserved.

Development of an in-line Raman spectroscopic method for continuous API quantification during twin-screw wet granulation.

PubMed

Harting, Julia; Kleinebudde, Peter

2018-04-01

Raman spectroscopy was evaluated as a process analytical technology (PAT) tool for continuous API quantification during twin-screw wet granulation. Therefore, a Raman probe was implemented in front of the granulator barrel. This setup enabled the collection of Raman spectra upon a constant granule flow. To develop an in-line PLS calibration model, eight binary mixtures of the API and lactose monohydrate with API contents between 5 and 50% were pre-blended and granulated in a twin-screw granulator with a screw speed of 150 rpm and a powder feed rate of 40 g/min. Water was used as a granulation liquid with different liquid to solid ratios depending on the API content. Ibuprofen and diclofenac sodium were chosen as model drugs and separated PLS models were built for each API. The predictive performance of the developed PLS models was determined by granulating and monitoring new test samples containing different API concentrations. This evaluation showed that the models were able to predict the API concentration with an RMSEP of 0.59% for ibuprofen and 1.5% for diclofenac sodium. In a second part, the developed in-line Raman spectroscopic method was used to determine the API concentration during a split feeding process. Therefore, the API and lactose monohydrate were added by two independently adjustable feeders into the twin-screw granulator barrel. The in-line spectroscopy analysis which was verified by UV-analysis indicated that the mixing ability of the twin-screw granulator was good for the used settings and all adjusted API concentrations. Copyright © 2018 Elsevier B.V. All rights reserved.

To Evaluate the Effect of Solvents and Different Relative Humidity Conditions on Thermal and Rheological Properties of Microcrystalline Cellulose 101 Using METHOCEL™ E15LV as a Binder.

PubMed

Jagia, Moksh; Trivedi, Maitri; Dave, Rutesh H

2016-08-01

The solvent used for preparing the binder solution in wet granulation can affect the granulation end point and also impact the thermal, rheological, and flow properties of the granules. The present study investigates the effect of solvents and percentage relative humidity (RH) on the granules of microcrystalline cellulose (MCC) with hydroxypropyl methyl cellulose (HPMC) as the binder. MCC was granulated using 2.5% w/w binder solution in water and ethanol/water mixture (80:20 v/v). Prepared granules were dried until constant percentage loss on drying, sieved, and further analyzed. Dried granules were exposed to different percentage RH for 48 h at room temperature. Powder rheometer was used for the rheological and flow characterization, while thermal effusivity and differential scanning calorimeter were used for thermal analysis. The thermal effusivity values for the wet granules showed a sharp increase beginning 50% w/w binder solution in both cases, which reflected the over-wetting of granules. Ethanol/water solvent batches showed greater resistance to flow as compared to the water solvent batches in the wet granule stage, while the reverse was true for the dried granule stage, as evident from the basic flowability energy values. Although the solvents used affected the equilibration kinetics of moisture content, the RH-exposed granules remained unaffected in their flow properties in both cases. This study indicates that the solvents play a vital role on the rheology and flow properties of MCC granules, while the different RH conditions have little or no effect on them for the above combination of solvent and binder.

Effects of pharmaceutical processing on pepsin activity during the formulation of solid dosage forms.

PubMed

Kristó, Katalin; Pintye-Hódi, Klára

2013-02-01

The main aim of this study was to investigate the effects of pharmaceutical technological methods on pepsin activity during the formulation of solid dosage forms. The circumstances of direct compression and wet granulation were modeled. During direct compression, the heat and the compression force must be taken into consideration. The effects of these parameters were investigated in three materials (pure pepsin, and 1:1 (w/w) pepsin-tartaric acid and 1:1 (w/w) pepsin-citric acid powder mixtures). It was concluded that direct compression is appropriate for the formulation of solid dosage forms containing pepsin through application without acids or with acids at low compression force. The effects of wet granulation were investigated with a factorial design for the same three materials. The factors were time, temperature and moisture content. There was no significant effect of the factors when acids were not applied. Temperature was a significant factor when acids were applied. The negative effect was significantly higher for citric acid than for tartaric acid. It was found that wet granulation can be utilized for the processing of pepsin into solid dosage forms under well-controlled circumstances. The application of citric acid is not recommended during the formulation of solid dosage forms through wet granulation. A mathematically based optimization may be necessary for preformulation studies of the preparation of dosage forms containing sensitive enzymes.

Effect of formulation and process variables on lipid based sustained release tablets via continuous twin screw granulation: A comparative study.

PubMed

Kallakunta, Venkata Raman; Tiwari, Roshan; Sarabu, Sandeep; Bandari, Suresh; Repka, Michael A

2018-05-14

The current study's aim is to prepare lipid based sustained release tablets via a twin-screw granulation technique and compare those dosage forms with conventional techniques, namely wet granulation and direct compression. The granules were successfully manufactured in a single-step, continuous twin-screw granulation process with a low proportion of binder (Klucel™ EF, HPC SSL) using Compritol® 888 ATO, Precirol® ATO 5 and Geleol™ as sustained release agents. The granules prepared showed good flow characteristics and compaction properties. DSC and XRD studies were conducted to characterize the granules prepared via a twin-screw granulation method and the results demonstrated the crystalline nature of lipids within the granules. FTIR data indicated that there were no interactions with the formulation components investigated. The formulations developed by all three methods were compressed into tablets with a mechanical strength of 14-16 KP. The tablets formulated were characterized for physicochemical properties, in vitro drug release studies, water uptake and erosion studies. These results showed that the drug was not completely released after 24 h for tablets developed by the wet granulation process using all three lipids. The tablets prepared by the direct compression method demonstrated a burst release within 8 to 10 h from Precirol ATO 5® and Geleol™ formulations compared to Compritol® 888 ATO. However, tablets prepared using twin-screw granulation exhibited sustained release of the drug over 24 h and the water uptake and erosion results were in accordance with dissolution data. Stability data for 45 days at accelerated conditions (40 °C/75% RH) showed similar release profiles with ƒ2 values above 50 for all of the twin screw granulation formulations, indicating the suitability of the process for formulating sustained release tablets. These findings of a single-step, continuous twin-screw granulation process are novel and demonstrate new opportunities for development of sustained release tablets. Copyright © 2017. Published by Elsevier B.V.

Characterization and taste-masking evaluation of acetaminophen granules: comparison between different preparation methods in a high-shear mixer.

PubMed

Albertini, Beatrice; Cavallari, Cristina; Passerini, Nadia; Voinovich, Dario; González-Rodríguez, Marisa L; Magarotto, Lorenzo; Rodriguez, Lorenzo

2004-02-01

The aim of this study was to prepare and to investigate acetaminophen taste-masked granules obtained in a high-shear mixer using three different wet granulation methods (method A: water granulation, method B: granulation with a polyvinylpyrrolidone (PVP) binding solution and method C: steam granulation). The studied formulation was: acetaminophen 15%, alpha-lactose monohydrate 30%, cornstarch 45%, polyvinylpyrrolidone K30 5% and orange flavour 5% (w/w). In vitro dissolution studies, performed at pH 6.8, showed that steam granules enabled the lower dissolution rate in comparison to the water and binding solution granules; these results were then confirmed by their lower surface reactivity (D(R)) during the dissolution process. Moreover, the results of the gustatory sensation test performed by six volunteers confirmed the taste-masking effects of the granules, especially steam granules (P<0.001). Morphological, fractal and porosity analysis were then performed to explain the dissolution profiles and the results of the gustatory sensation test. Scanning electron microscopy (SEM) analysis revealed the smoother and the more regular surface of steam granules with respect to the samples obtained using methods A and B; these results were also confirmed by their lower fractal dimension (D(s)) and porosity values. Finally, differential scanning calorimetry (DSC) results showed a shift of the melting point of the drug, which was due to the simple mixing of the components and not to the granulation processes. In conclusion, the steam granulation technique resulted a suitable method to comply the purpose of this work, without modifying the availability of the drug.

The Impact of Granule Density on Tabletting and Pharmaceutical Product Performance.

PubMed

van den Ban, Sander; Goodwin, Daniel J

2017-05-01

The impact of granule densification in high-shear wet granulation on tabletting and product performance was investigated, at pharmaceutical production scale. Product performance criteria need to be balanced with the need to deliver manufacturability criteria to assure robust industrial scale tablet manufacturing processes. A Quality by Design approach was used to determine in-process control specifications for tabletting, propose a design space for disintegration and dissolution, and to understand the permitted operating limits and required controls for an industrial tabletting process. Granules of varying density (filling density) were made by varying water amount added, spray rate, and wet massing time in a design of experiment (DoE) approach. Granules were compressed into tablets to a range of thicknesses to obtain tablets of varying breaking force. Disintegration and dissolution performance was evaluated for the tablets made. The impact of granule filling density on tabletting was rationalised with compressibility, tabletability and compactibility. Tabletting and product performance criteria provided competing requirements for porosity. An increase in granule filling density impacted tabletability and compactability and limited the ability to achieve tablets of adequate mechanical strength. An increase in tablet solid fraction (decreased porosity) impacted disintegration and dissolution. An attribute-based design space for disintegration and dissolution was specified to achieve both product performance and manufacturability. The method of granulation and resulting granule filling density is a key design consideration to achieve both product performance and manufacturability required for modern industrial scale pharmaceutical product manufacture and distribution.

The influence of granulation on super disintegrant performance.

PubMed

Zhao, Na; Augsburger, Larry L

2006-02-01

The purpose of this study is to identify the causes of efficiency loss of super disintegrants following granulation or reworking. Two processes, precompression and prewetting, were proposed to simulate the processes during dry and wet granulation, respectively. The disintegration efficiency of the resulting disintegrant granules was tested in model formulations composed of dicalcium phosphate and lactose with the unprocessed disintegrants as controls. No significant difference was shown in the intrinsic swelling and the water uptake abilities of all super disintegrants following dry granulation. However, a significant decrease was observed for both Primojel and Polyplasdone XL10 in the rate of water being absorbed into the tablet matrix following wet granulation, but not for Ac-Di-Sol. United States Pharmacopeia (USP) disintegration testing without disc revealed a significant increase in disintegration time for tablets formulated with dry granulated Primojel and Polyplasdone XL10 and all wet granulated disintegrants. The increase in particle size following granulation appears to be the cause of the loss in disintegration efficiency. In conclusion, Ac-Di-Sol is less affected by both precompression and prewetting. The efficiency of Primojel and Polyplasdone XL10 is highly dependent on their particle size. Descreasing the particle size tends to increase their efficiency. Due to the size increase following granulation, a higher addition level of super disintegrant is required to ensure fast and uniform disintegration of tablets prepared by granulation.

Effect of surfactants or a water soluble polymer on the crystal transition of clarithromycin during a wet granulation process.

PubMed

Nozawa, Kenji; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2015-11-10

To generate products containing a stable form of clarithromycin (CAM) (form II) regardless of the initial crystal form of CAM or type of granulation solvent, the effects of five surfactants, or a water-soluble polymer (macrogol 400) were determined on the crystal transition of CAM. The metastable form (form I) was kneaded with water, after adding surfactants, or a water-soluble polymer. Form II was also kneaded with ethanol, after adding the same additives. The resulting samples were analyzed by powder X-ray diffraction. Form I was completely converted to form II by a wet granulation using water with additives bearing polyoxyethylene chains such as polysorbate 80 (PS80), polyoxyl 40 stearate or macrogol 400. The granulation of the form II using ethanol with these additives did not result in a crystal transition to form I. Furthermore, CAM tablets were manufactured using granules with PS80, and these crystal forms and dissolution behaviors were investigated. As a result, the wet granulation of CAM with PS80 gave CAM tablets containing only form II and PS80 did not have any adverse effects on tablet characteristics. Therefore, these data suggests that the crystal form of CAM can be controlled to be form II using a wet granulation process with additives bearing polyoxyethylene chains regardless of the initial crystal form of CAM or type of granulation solvent. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of the chopper on granules from wet high-shear granulation using a PMA-1 granulator.

PubMed

Briens, Lauren; Logan, Ryan

2011-12-01

Chopper presence and then chopper speed was varied during wet high shear granulation of a placebo formulation using a PMA-1 granulator while also varying the impeller speed. The granules were extensively analyzed for differences due to the chopper. The effect of the chopper on the granules varied with impeller speed from no effect at a low impeller speed of 300 rpm to flow interruptions at an impeller speed of 700 rpm to minimal impact at very high impeller speeds as caking at the bowl perimeter obscured the effect of the chopper on the flow pattern. Differences in the granule flowability were minimal. However, it was concluded that the largest fraction of optimal granules would be obtained at an impeller speed of 700 rpm with the chopper at 1,000 rpm allowing balances between flow establishment, segregation, and centrifugal forces.

Formulation and evaluation of a montelukast sodium orally disintegrating tablet with a similar dissolution profile as the marketed product.

PubMed

Chen, Yong; Feng, Tingting; Li, Yong; Du, Bin; Weng, Weiyu

2017-03-01

A major challenge of orally disintegrating tablet (ODT) development is predicting its bioequivalence to its corresponding marketed product. Therefore, comparing ODT dissolution profiles to those of the corresponding marketed product is very important. The objective of this study was to develop a 5.2-mg montelukast sodium (MS) ODT with a similar dissolution profile to that of the marketed chewable tablet. Dissolution profiles were examined in different media to screen each formulation. We found that MS dissolution from ODTs in acidic medium heavily depended on manufacturing methods. All MS ODTs prepared using direct compression rapidly disintegrated in acidic medium. However, dispersed MS powders aggregated into sticky masses, resulting in slow dissolution. In contrast, MS ODTs prepared using wet granulation had much faster dissolution rates in acidic medium with no obvious aggregation. Additionally, the optimized formulation, prepared using wet granulation, displayed similar dissolution profiles to the marketed reference in all four types of media examined (f 2  >   50). The in vitro disintegration time of the optimized ODT was 9.5 ± 2.4 s, which meets FDA requirements. In conclusion, the wet granulation preparation method of MS ODTs resulted in a product with equivalent dissolution profiles as those of the marketed product.

Does the performance of wet granulation and tablet hardness affect the drug dissolution profile of carvedilol in matrix tablets?

PubMed

Košir, Darjan; Ojsteršek, Tadej; Vrečer, Franc

2018-06-14

Wet granulation is mostly used process for manufacturing matrix tablets. Compared to the direct compression method, it allows for a better flow and compressibility properties of compression mixtures. Granulation, including process parameters and tableting, can influence critical quality attributes (CQAs) of hydrophilic matrix tablets. One of the most important CQAs is the drug release profile. We studied the influence of granulation process parameters (type of nozzle and water quantity used as granulation liquid) and tablet hardness on the drug release profile. Matrix tablets contained HPMC K4M hydrophilic matrix former and carvedilol as a model drug. The influence of selected HPMC characteristics on the drug release profile was also evaluated using two additional HPMC batches. For statistical evaluation, partial least square (PLS) models were generated for each time point of the drug release profile using the same number of latent factors. In this way, it was possible to evaluate how the importance of factors influencing drug dissolution changes in dependence on time throughout the drug release profile. The results of statistical evaluation show that the granulation process parameters (granulation liquid quantity and type of nozzle) and tablet hardness significantly influence the release profile. On the other hand, the influence of HPMC characteristics is negligible in comparison to the other factors studied. Using a higher granulation liquid quantity and the standard nozzle type results in larger granules with a higher density and lower porosity, which leads to a slower drug release profile. Lower tablet hardness also slows down the release profile.

Influence of wet granulation and lubrication on the powder and tableting properties of codried product of microcrystalline cellulose with beta-cyclodextrin.

PubMed

Wu, J; Ho, H; Sheu, M

2001-01-01

The individual influence of wet granulation and lubrication on the powder and tableting properties of codried product of microcrystalline cellulose (MCC) with beta-cyclodextrin (beta-CD) was examined in this study. Avicel PH 101 and 301 were included for comparison. The codried product, Avicel PH 101 and 301 were granulated with water, and the granules were milled to retain three different size fractions: 37-60 microm, 60-150 microm, and 150-420 microm. The original Avicels and codried product were lubricated with magnesium stearate in three different percentages (0.2, 0.5, and 1.0%). The results showed that the powder flowability and disintegration of codried product and Avicels were significantly improved after wet granulation. However, the compactibility of codried product and Avicels decreased with increasing particle size. Nevertheless, the compactibility of the codried excipient after granulation was still better than the non-granulated Avicel PH 101 and 301. On the other hand, codried product and Avicels were sensitive to lubrication and resulted in decreasing compactibility and increasing disintegration. Because of the rounder shape of particles, the codried excipient was more sensitive to magnesium stearate and produced weaker tablets than did Avicels.

Determining the Influence of Granule Size on Simulation Parameters and Residual Shear Stress Distribution in Tablets by Combining the Finite Element Method into the Design of Experiments.

PubMed

Hayashi, Yoshihiro; Kosugi, Atsushi; Miura, Takahiro; Takayama, Kozo; Onuki, Yoshinori

2018-01-01

The influence of granule size on simulation parameters and residual shear stress in tablets was determined by combining the finite element method (FEM) into the design of experiments (DoE). Lactose granules were prepared using a wet granulation method with a high-shear mixer and sorted into small and large granules using sieves. To simulate the tableting process using the FEM, parameters simulating each granule were optimized using a DoE and a response surface method (RSM). The compaction behavior of each granule simulated by FEM was in reasonable agreement with the experimental findings. Higher coefficients of friction between powder and die/punch (μ) and lower by internal friction angle (α y ) were generated in the case of small granules, respectively. RSM revealed that die wall force was affected by α y . On the other hand, the pressure transmissibility rate of punches value was affected not only by the α y value, but also by μ. The FEM revealed that the residual shear stress was greater for small granules than for large granules. These results suggest that the inner structure of a tablet comprising small granules was less homogeneous than that comprising large granules. To evaluate the contribution of the simulation parameters to residual stress, these parameters were assigned to the fractional factorial design and an ANOVA was applied. The result indicated that μ was the critical factor influencing residual shear stress. This study demonstrates the importance of combining simulation and statistical analysis to gain a deeper understanding of the tableting process.

Dextrose monohydrate as a non-animal sourced alternative diluent in high shear wet granulation tablet formulations.

PubMed

Mitra, Biplob; Wolfe, Chad; Wu, Sy-Juen

2018-05-01

The feasibility of dextrose monohydrate as a non-animal sourced diluent in high shear wet granulation (HSWG) tablet formulations was determined. Impacts of granulation solution amount and addition time, wet massing time, impeller speed, powder and solution binder, and dry milling speed and screen opening size on granule size, friability and density, and tablet solid fraction (SF) and tensile strength (TS) were evaluated. The stability of theophylline tablets TS, disintegration time (DT) and in vitro dissolution were also studied. Following post-granulation drying at 60 °C, dextrose monohydrate lost 9% water and converted into the anhydrate form. Higher granulation solution amounts and faster addition, faster impeller speeds, and solution binder produced larger, denser and stronger (less friable) granules. All granules were compressed into tablets with acceptable TS. Contrary to what is normally observed, denser and larger granules (at ≥21% water level) produced tablets with a higher TS. The TS of the weakest tablets increased the most after storage at both 25 °C/60% RH and 40 °C/75% RH. Tablet DT was higher for stronger granules and after storage. Tablet dissolution profiles for 21% or less water were comparable and did not change on stability. However, the dissolution profile for tablets prepared with 24% water was slower initially and continued to decrease on stability. The results indicate a granulation water amount of not more than 21% is required to achieve acceptable tablet properties. This study clearly demonstrated the utility of dextrose monohydrate as a non-animal sourced diluent in a HSWG tablet formulation.

Manufacturing of novel low-cost adsorbent: Co-granulation of limestone and coffee waste.

PubMed

Iakovleva, Evgenia; Sillanpää, Mika; Maydannik, Philipp; Liu, Jiang Tao; Allen, Stephen; Albadarin, Ahmad B; Mangwandi, Chirangano

2017-12-01

Limestone and coffee waste were used during the wet co-granulation process for the production of efficient adsorbents to be used in the removal of anionic and cationic dyes. The adsorbents were characterized using different analytical techniques such as XRD, SEM, FTIR, organic elemental analysis, the nitrogen adsorption method, with wettability, strength and adsorption tests. The adsorption capacity of granules was determined by removal of methylene blue (MB) and orange II (OR) from single and mixed solutions. In the mixed solution, co-granules removed 100% of MB and 85% of OR. The equilibria were established after 6 and 480 h for MB and OR, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

New gentle-wing high-shear granulator: impact of processing variables on granules and tablets characteristics of high-drug loading formulation using design of experiment approach.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shdefat, Ramadan I

2017-10-01

The aim of this work was to study the application of design of experiment (DoE) approach in defining design space for granulation and tableting processes using a novel gentle-wing high-shear granulator. According to quality-by-design (QbD) prospective, critical attributes of granules, and tablets should be ensured by manufacturing process design. A face-centered central composite design has been employed in order to investigate the effect of water amount (X 1 ), impeller speed (X 2 ), wet massing time (X 3 ), and water addition rate (X 4 ) as independent process variables on granules and tablets characteristics. Acetaminophen was used as a model drug and granulation experiments were carried out using dry addition of povidone k30. The dried granules have been analyzed for their size distribution, density, and flow pattern. Additionally, the produced tablets have been investigated for; weight uniformity, breaking force, friability and percent capping, disintegration time, and drug dissolution. Results of regression analysis showed that water amount, impeller speed and wet massing time have significant (p < .05) effect on granules and tablets characteristics. However, the water amount had the most pronounced effect as indicated by its higher parameter estimate. On the other hand, water addition rate showed a minimal impact on granules and tablets properties. In conclusion, water amount, impeller speed, and wet massing time could be considered as critical process variables. Thus, understanding the relationship between these variables and quality attributes of granules and corresponding tablets provides the basis for adjusting granulation variables in order to optimize product performance.

Multimodal approach to characterization of hydrophilic matrices manufactured by wet and dry granulation or direct compression methods.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Obrał, Jadwiga; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Jachowicz, Renata; Wyszogrodzka, Gabriela; Klaja, Jolanta; Dorożyński, Przemysław P

2016-02-29

The purpose of the research was to investigate the effect of the manufacturing process of the controlled release hydrophilic matrix tablets on their hydration behavior, internal structure and drug release. Direct compression (DC) quetiapine hemifumarate matrices and matrices made of powders obtained by dry granulation (DG) and high shear wet granulation (HS) were prepared. They had the same quantitative composition and they were evaluated using X-ray microtomography, magnetic resonance imaging and biorelevant stress test dissolution. Principal results concerned matrices after 2 h of hydration: (i) layered structure of the DC and DG hydrated tablets with magnetic resonance image intensity decreasing towards the center of the matrix was observed, while in HS matrices layer of lower intensity appeared in the middle of hydrated part; (ii) the DC and DG tablets retained their core and consequently exhibited higher resistance to the physiological stresses during simulation of small intestinal passage than HS formulation. Comparing to DC, HS granulation changed properties of the matrix in terms of hydration pattern and resistance to stress in biorelevant dissolution apparatus. Dry granulation did not change these properties-similar hydration pattern and dissolution in biorelevant conditions were observed for DC and DG matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

Artificial Intelligence Tools for Scaling Up of High Shear Wet Granulation Process.

PubMed

Landin, Mariana

2017-01-01

The results presented in this article demonstrate the potential of artificial intelligence tools for predicting the endpoint of the granulation process in high-speed mixer granulators of different scales from 25L to 600L. The combination of neurofuzzy logic and gene expression programing technologies allowed the modeling of the impeller power as a function of operation conditions and wet granule properties, establishing the critical variables that affect the response and obtaining a unique experimental polynomial equation (transparent model) of high predictability (R 2 > 86.78%) for all size equipment. Gene expression programing allowed the modeling of the granulation process for granulators of similar and dissimilar geometries and can be improved by implementing additional characteristics of the process, as composition variables or operation parameters (e.g., batch size, chopper speed). The principles and the methodology proposed here can be applied to understand and control manufacturing process, using any other granulation equipment, including continuous granulation processes. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Development of sustained release capsules containing "coated matrix granules of metoprolol tartrate".

PubMed

Siddique, Sabahuddin; Khanam, Jasmina; Bigoniya, Papiya

2010-09-01

The objective of this investigation was to prepare sustained release capsule containing coated matrix granules of metoprolol tartrate and to study its in vitro release and in vivo absorption. The design of dosage form was performed by choosing hydrophilic hydroxypropyl methyl cellulose (HPMC K100M) and hydrophobic ethyl cellulose (EC) polymers as matrix builders and Eudragit® RL/RS as coating polymers. Granules were prepared by composing drug with HPMC K100M, EC, dicalcium phosphate by wet granulation method with subsequent coating. Optimized formulation of metoprolol tartrate was formed by using 30% HPMC K100M, 20% EC, and ratio of Eudragit® RS/RL as 97.5:2.5 at 25% coating level. Capsules were filled with free flowing optimized granules of uniform drug content. This extended the release period upto 12 h in vitro study. Similarity factor and mean dissolution time were also reported to compare various dissolution profiles. The network formed by HPMC and EC had been coupled satisfactorily with the controlled resistance offered by Eudragit® RS. The release mechanism of capsules followed Korsemeyer-Peppas model that indicated significant contribution of erosion effect of hydrophilic polymer. Biopharmaceutical study of this optimized dosage form in rabbit model showed 10 h prolonged drug release in vivo. A close correlation (R(2) = 0.9434) was established between the in vitro release and the in vivo absorption of drug. The results suggested that wet granulation with subsequent coating by fluidized bed technique, is a suitable method to formulate sustained release capsules of metoprolol tartrate and it can perform therapeutically better than conventional immediate release dosage form.

Massing in high shear wet granulation can simultaneously improve powder flow and deteriorate powder compaction: a double-edged sword.

PubMed

Shi, Limin; Feng, Yushi; Sun, Changquan Calvin

2011-05-18

The influence of massing during high shear wet granulation (HSWG) process on granule properties and performance was investigated using microcrystalline cellulose (MCC). Massing time varied from 0 to 40 min while other factors were fixed. Granule physical properties, including morphology, size, porosity, and specific surface area (SSA), were characterized. Changes in powder properties were profound in the first 10 min of massing but negligible beyond 10 min. With 10 min of massing, granule tabletability decreased by 75% while flowability increased by 75%. The significantly deteriorated tabletability and improved flowability resulted from dramatic changes in granule morphology, porosity, and SSA. The results confirm that massing time is a key process parameter in HSWG, and it must be carefully evaluated and controlled during process development, scale up, and manufacturing. Copyright © 2011 Elsevier B.V. All rights reserved.

Evaluation of the impact of sodium lauryl sulfate source variability on solid oral dosage form development.

PubMed

Qiang, Dongmei; Gunn, Jocelyn A; Schultz, Leon; Li, Z Jane

2010-12-01

The objective of this study was to investigate the effects of sodium lauryl sulfate (SLS) from different sources on solubilization/wetting, granulation process, and tablet dissolution of BILR 355 and the potential causes. The particle size distribution, morphology, and thermal behaviors of two pharmaceutical grades of SLS from Spectrum and Cognis were characterized. The surface tension and drug solubility in SLS solutions were measured. The BILR 355 tablets were prepared by a wet granulation process and the dissolution was evaluated. The critical micelle concentration was lower for Spectrum SLS, which resulted in a higher BILR 355 solubility. During wet granulation, less water was required to reach the same end point using Spectrum than Cognis SLS. In general, BILR 355 tablets prepared with Spectrum SLS showed a higher dissolution than the tablets containing Cognis SLS. Micronization of SLS achieved the same improved tablet dissolution as micronized active pharmaceutical ingredient. The observed differences in wetting and solubilization were likely due to the different impurity levels in SLS from two sources. This study demonstrated that SLS from different sources could have significant impact on wet granulation process and dissolution. Therefore, it is critical to evaluate SLS properties from different suppliers, and then identify optimal formulation and process parameters to ensure robustness of drug product manufacture process and performance.

Latent structure analysis in the pharmaceutical process of tablets prepared by wet granulation.

PubMed

Uehara, Naoto; Hayashi, Yoshihiro; Mochida, Hiroshi; Otoguro, Saori; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2016-01-01

Granule characteristics are some of the important intermediate qualities that determine tablet properties. However, the relationships between granule and tablet characteristics are poorly understood. The aim of this study was to elucidate relationships among formulation factors, granule characteristics, and tablet properties using a non-linear response surface method (RSM) incorporating a thin-plate spline interpolation (RSM-S) and a Bayesian network (BN). Tablets containing lactose (Lac), cornstarch (CS), and microcrystalline cellulose (MCC) were prepared by wet granulation. Ten formulations were prepared by an extreme vertices design. The angle of repose (Y 1 ), compressibility (Y 2 ), cohesion force (Y 3 ), internal friction angle (Y 4 ), and mean particle size (Y 5 ) were measured as granule characteristics. Tensile strength (TS) and disintegration time (DT) were measured as tablet properties. RSM-S results showed that TS increased with increasing amounts of MCC and Lac. DT decreased with increasing amounts of MCC and CS. The optimal BN models were predicted using four evaluation indices -Y 3 was shown to be the most important factor for TS, whereas Y 2 , Y 3 , and Y 4 were relatively important for predicting DT. Moreover, tablets with excellent tablet properties (i.e. high TS and low DT) were produced by relatively high Y 1 , low Y 2 , high Y 3 , high Y 4 , and middle Y 5 values, and resulted from the middle of MCC, middle-to-low CS, low Lac, and middle-to-low magnesium stearate (Mg-St) amounts. The RSM-S and BN techniques are useful for revealing complex relationships among formulation factors, granule characteristics, and tablet properties.

An innovative method for the preparation of high API-loaded hollow spherical granules for use in controlled-release formulation.

PubMed

Asada, Takumi; Kobiki, Mitsuaki; Ochiai, Yasushi; Iwao, Yasunori; Itai, Shigeru

2017-05-15

The aim of this study was to prepare controlled-release (CR) granules with suitable particle strength, flowability, particle size distribution (PSD) and density characteristics for blending with other excipients. We also wanted these CR granules to contain large quantities of active pharmaceutical ingredient (API). A high shear mixer was used to mix an API with various polymers at various feed ratios, and the resulting granulated materials were sprayed with solvent. The wet granules were dried using a fluidized bed dryer to give CR granules. The API content of the granules was determined to be 95wt%. The granules were found to be spherical in shape with smooth surfaces by scanning electron microscopy. The inner structure of each granule was determined to be hollow by X-ray computed tomography, highlighting the unusual mechanism of this granulation process. The PSD of the granules was found to be dependent on that of the constituent polymer, and a narrow PSD was obtained by adjusting the PSD of the polymer. The dissolution profile of the granules was also dependent on the constituent polymer. Taken together, these results show that we have successfully developed a new manufacturing technology for the simple and low-cost preparation of ideal CR granules. Copyright © 2017 Elsevier B.V. All rights reserved.

[Application of quality by design in granulation process for Ginkgo leaf tablet (Ⅲ)： process control strategy based on design space].

PubMed

Cui, Xiang-Long; Xu, Bing; Sun, Fei; Dai, Sheng-Yun; Shi, Xin-Yuan; Qiao, Yan-Jiang

2017-03-01

In this paper, under the guidance of quality by design (QbD) concept, the control strategy of the high shear wet granulation process of the ginkgo leaf tablet based on the design space was established to improve the process controllability and product quality consistency. The median granule size (D50) and bulk density (Da) of granules were identified as critical quality attributes (CQAs) and potential critical process parameters (pCPPs) were determined by the failure modes and effect analysis (FMEA). The Plackeet-Burmann experimental design was used to screen pCPPs and the results demonstrated that the binder amount, the wet massing time and the wet mixing impeller speed were critical process parameters (CPPs). The design space of the high shear wet granulation process was developed within pCPPs range based on the Box-Behnken design and quadratic polynomial regression models. ANOVA analysis showed that the P-values of model were less than 0.05 and the values of lack of fit test were more than 0.1, indicating that the relationship between CQAs and CPPs could be well described by the mathematical models. D₅₀ could be controlled within 170 to 500 μm, and the bulk density could be controlled within 0.30 to 0.44 g•cm⁻³ by using any CPPs combination within the scope of design space. Besides, granules produced by process parameters within the design space region could also meet the requirement of tensile strength of the ginkgo leaf tablet.. Copyright© by the Chinese Pharmaceutical Association.

In-line moisture monitoring in fluidized bed granulation using a novel multi-resonance microwave sensor.

PubMed

Peters, Johanna; Bartscher, Kathrin; Döscher, Claas; Taute, Wolfgang; Höft, Michael; Knöchel, Reinhard; Breitkreutz, Jörg

2017-08-01

Microwave resonance technology (MRT) is known as a process analytical technology (PAT) tool for moisture measurements in fluid-bed granulation. It offers a great potential for wet granulation processes even where the suitability of near-infrared (NIR) spectroscopy is limited, e.g. colored granules, large variations in bulk density. However, previous sensor systems operating around a single resonance frequency showed limitations above approx. 7.5% granule moisture. This paper describes the application of a novel sensor working with four resonance frequencies. In-line data of all four resonance frequencies were collected and further processed. Based on calculation of density-independent microwave moisture values multiple linear regression (MLR) models using Karl-Fischer titration (KF) as well as loss on drying (LOD) as reference methods were build. Rapid, reliable in-process moisture control (RMSEP≤0.5%) even at higher moisture contents was achieved. Copyright © 2017 Elsevier B.V. All rights reserved.

Conceptual framework for model-based analysis of residence time distribution in twin-screw granulation.

PubMed

Kumar, Ashish; Vercruysse, Jurgen; Vanhoorne, Valérie; Toiviainen, Maunu; Panouillot, Pierre-Emmanuel; Juuti, Mikko; Vervaet, Chris; Remon, Jean Paul; Gernaey, Krist V; De Beer, Thomas; Nopens, Ingmar

2015-04-25

Twin-screw granulation is a promising continuous alternative for traditional batchwise wet granulation processes. The twin-screw granulator (TSG) screws consist of transport and kneading element modules. Therefore, the granulation to a large extent is governed by the residence time distribution within each module where different granulation rate processes dominate over others. Currently, experimental data is used to determine the residence time distributions. In this study, a conceptual model based on classical chemical engineering methods is proposed to better understand and simulate the residence time distribution in a TSG. The experimental data were compared with the proposed most suitable conceptual model to estimate the parameters of the model and to analyse and predict the effects of changes in number of kneading discs and their stagger angle, screw speed and powder feed rate on residence time. The study established that the kneading block in the screw configuration acts as a plug-flow zone inside the granulator. Furthermore, it was found that a balance between the throughput force and conveying rate is required to obtain a good axial mixing inside the twin-screw granulator. Although the granulation behaviour is different for other excipients, the experimental data collection and modelling methods applied in this study are generic and can be adapted to other excipients. Copyright © 2015 Elsevier B.V. All rights reserved.

Formulation design for optimal high-shear wet granulation using on-line torque measurements.

PubMed

Cavinato, Mauro; Bresciani, Massimo; Machin, Marianna; Bellazzi, Guido; Canu, Paolo; Santomaso, Andrea C

2010-03-15

An alternative procedure for achieving formulation design in a high-shear wet granulation process has been developed. Particularly, a new formulation map has been proposed which describes the onset of a significant granule growth as a function of the formulation variables (diluent, dry and liquid binder). Granule growth has been monitored using on-line impeller torque and evaluated as changes in granule particle size distribution with respect to the dry formulation. It is shown how the onset of granule growth is denoted by an abrupt increase in the torque value requires the amount of binder liquid added to be greater than a certain threshold that is identified here as 'minimum liquid volume'. This minimum liquid volume is determined as a function of dry binder type, amount, hygroscopicity and particle size distribution of diluent. It is also demonstrated how this formulation map can be constructed from independent measurements of binder glass transition temperatures using a static humidity conditioning system. 2009 Elsevier B.V. All rights reserved.

Monitoring of multiple solvent induced form changes during high shear wet granulation and drying processes using online Raman spectroscopy.

PubMed

Reddy, Jay Poorna; Jones, John W; Wray, Patrick S; Dennis, Andrew B; Brown, Jonathan; Timmins, Peter

2018-04-25

Form changes during drug product processing can be a risk to the final product quality in terms of chemical stability and bioavailability. In this study, online Raman spectroscopy was used to monitor the form changes in real time during high shear wet granulation of Compound A, a highly soluble drug present at a high drug load in an extended release formulation. The effect of water content, temperature, wet massing time and drying technique on the degree of drug transformation were examined. A designed set of calibration standards were employed to develop quantitative partial least square regression models to predict the concentration of each drug form during both wet granulation and the drying process. Throughout all our experiments we observed complex changes of the drug form during granulation, manifest as conversions between the initial non-solvated form of Compound A, the hemi-hydrate form and the "apparent" amorphous form (dissolved drug). The online Raman data demonstrate that the non-solvated form converts to an "apparent" amorphous form (dissolved drug) due to drug dissolution with no appearance of the hemi-hydrate form during water addition stage. The extent of conversion of the non-solvated form was governed by the amount of water added and the rate of conversion was accelerated at higher temperatures. Interestingly, in the wet massing zone, the formation of the hemi-hydrate form was observed at a rate equivalent to the rate of depletion of the non-solvated form with no change in the level of the "apparent amorphous" form generated. The level of hemi-hydrate increased with an increase in wet massing time. The drying process had a significant effect on the proportion of each form. During tray drying, changes in drug form continued for hours. In contrast fluid bed drying appeared to lock the final proportions of drug form product attained during granulation, with comparatively small changes observed during drying. In conclusion, it was possible to simultaneously monitor the three forms in real time during wet granulation and drying using online Raman spectroscopy. The results regarding the effect of process parameters on the degree of transformation are critical for designing a robust process that ensures a consistent form in the final drug product. Copyright © 2018 Elsevier B.V. All rights reserved.

Enhancement of ibuprofen dissolution via wet granulation with beta-cyclodextrin.

PubMed

Ghorab, M K; Adeyeye, M C

2001-08-01

The purpose was to investigate the effect of wet granulation with beta-cyclodextrin (betaCD) on the enhancement of ibuprofen (IBU) dissolution. The effect of the granulation variables on the physical properties as well as the dissolution of tablets prepared from these granules was also examined. Granulation was performed using three granulating solvents: water, ethanol (95 vol%), and isopropanol. Granules were either oven-dried for 2 h or air-dried for 3 days. The granules or respective physical mixtures were compressed into tablets. Powder X-ray diffraction showed that oven-dried granulation resulted in less amorphous entities thatfacilitated IBU-betaCD complexation in solution and enhanced the dissolution of the corresponding tablets compared to the physical mixture with or without oven drying. In contrast, air-dried granulation did not cause any differences in the X-ray diffraction pattern (crystallinity) or the dissolution compared to the physical mixture without drying. Isopropanol and water, as granulating solvents, enhanced the dissolution of the oven-dried batches more than ethanol. The Differential scanning calorimetry (DSC) and Thermogravimetric analysis (TGA) data showed that tablets prepared from oven-dried granules, but not air-dried granules, had lower AH values and percent loss in weight, respectively, than those prepared from the physical mixture as a result of the expulsion of the water molecules from the betaCD cavity and enhancement of the complexation in solution. These results showed that oven-dried granulation of IBU and betaCD provided faster IBU dissolution than the physical mixture; air-dried granulation did not substantially affect the dissolution of IBU.

Evaluation of beta-lactose, PVP K12 and PVP K90 as excipients to prepare piroxicam granules using two wet granulation techniques.

PubMed

Albertini, Beatrice; Cavallari, Cristina; Passerini, Nadia; González-Rodríguez, M L; Rodriguez, Lorenzo

2003-11-01

The present investigation aimed at evaluating the use of different excipients, beta-lactose and polyvinylpyrrolidone of two molecular weights (PVP K12 and PVP K90), in the production of improved release piroxicam granules, by wet granulation using both water and steam as granulation liquid. The formulations examined were: piroxicam (Px)/beta-lactose; Px/PVP K12 and Px/PVP K90, each one at a 1:9 weight ratio. The most significant difference between beta-lactose and PVP is that, using the first excipient, both steam and water granules were produced while, when PVP were employed, only steam granules were obtained. Image analysis revealed that beta-lactose steam granules had a larger surface area with respect to water granules, whereas lower values of this parameter were observed in PVP-s granules, confirming the Scanning Electron Microscopy micrographs and the fractal analysis results. As regards the enhancement of the dissolution profiles, the best result was obtained using beta-lactose steam granules followed by PVP K12 ones, even if the reactive dimension values indicated that during the dissolution process PVP K12 granules modified the surface more than beta-lactose granules. As regards PVP K90, this excipient was the one less influencing the granule morphology and the dissolution behaviour. Differential Scanning Calorimetry analysis suggested the partial amorphisation of the drug in the granules containing the three excipients. This result was then confirmed by X-ray powder diffraction analysis. Therefore, beta-lactose and PVP K12 could be proposed as useful excipients to enhance the dissolution rate of Px from granules prepared using the steam granulation technique.

Investigation of polymorphic transitions of piracetam induced during wet granulation.

PubMed

Potter, Catherine B; Kollamaram, Gayathri; Zeglinski, Jacek; Whitaker, Darren A; Croker, Denise M; Walker, Gavin M

2017-10-01

Piracetam was investigated as a model API which is known to exhibit a number of different polymorphic forms. It is freely soluble in water so the possibility exists for polymorphic transformations to occur during wet granulation. Analysis of the polymorphic form present during lab-scale wet granulation, using water as a granulation liquid, was studied with powder X-ray diffraction and Raman spectroscopy as off-line and inline analysis tools respectively. Different excipients with a range of hydrophilicities, aqueous solubilities and molecular weights were investigated to examine their influence on these solution-mediated polymorphic transitions and experimental results were rationalised using molecular modelling. Our results indicated that as an increasing amount of water was added to the as-received piracetam FIII, a greater amount of the API dissolved which recrystallised upon drying to the metastable FII(6.403) via a monohydrate intermediary. Molecular level analysis revealed that the observed preferential transformation of monohydrate to FII is linked with a greater structural similarity between the monohydrate and FII polymorph in comparison to FIII. The application of Raman spectroscopy as a process analytical technology (PAT) tool to monitor the granulation process for the production of the monohydrate intermediate as a precursor to the undesirable metastable form was demonstrated. Copyright © 2017 Elsevier B.V. All rights reserved.

A quality by design approach to scale-up of high-shear wet granulation process.

PubMed

Pandey, Preetanshu; Badawy, Sherif

2016-01-01

High-shear wet granulation is a complex process that in turn makes scale-up a challenging task. Scale-up of high-shear wet granulation process has been studied extensively in the past with various different methodologies being proposed in the literature. This review article discusses existing scale-up principles and categorizes the various approaches into two main scale-up strategies - parameter-based and attribute-based. With the advent of quality by design (QbD) principle in drug product development process, an increased emphasis toward the latter approach may be needed to ensure product robustness. In practice, a combination of both scale-up strategies is often utilized. In a QbD paradigm, there is also a need for an increased fundamental and mechanistic understanding of the process. This can be achieved either by increased experimentation that comes at higher costs, or by using modeling techniques, that are also discussed as part of this review.

High shear mixing granulation of ibuprofen and beta-cyclodextrin: effects of process variables on ibuprofen dissolution.

PubMed

Ghorab, Mohamed K; Adeyeye, Moji Christianah

2007-10-19

The aims of the study were to evaluate the effect of high shear mixer (HSM) granulation process parameters and scale-up on wet mass consistency and granulation characteristics. A mixer torque rheometer (MTR) was employed to evaluate the granulating solvents used (water, isopropanol, and 1:1 vol/vol mixture of both) based on the wet mass consistency. Gral 25 and mini-HSM were used for the granulation. The MTR study showed that the water significantly enhanced the beta-cyclodextrin (beta CD) binding tendency and the strength of liquid bridges formed between the particles, whereas the isopropanol/water mixture yielded more suitable agglomerates. Mini-HSM granulation with the isopropanol/water mixture (1:1 vol/vol) showed a reduction in the extent of torque value rise by increasing the impeller speed as a result of more breakdown of agglomerates than coalescence. In contrast, increasing the impeller speed of the Gral 25 resulted in higher torque readings, larger granule size, and consequently, slower dissolution. This was due to a remarkable rise in temperature during Gral granulation that reduced the isopropanol/water ratio in the granulating solvent as a result of evaporation and consequently increased the beta CD binding strength. In general, the HSM granulation retarded ibuprofen dissolution compared with the physical mixture because of densification and agglomeration. However, a successful HSM granulation scale-up was not achieved due to the difference in the solvent mixture's effect from 1 scale to the other.

Real-time assessment of critical quality attributes of a continuous granulation process.

PubMed

Fonteyne, Margot; Vercruysse, Jurgen; Díaz, Damián Córdoba; Gildemyn, Delphine; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas

2013-02-01

There exists the intention to shift pharmaceutical manufacturing of solid dosage forms from traditional batch production towards continuous production. The currently applied conventional quality control systems, based on sampling and time-consuming off-line analyses in analytical laboratories, would annul the advantages of continuous processing. It is clear that real-time quality assessment and control is indispensable for continuous production. This manuscript evaluates strengths and weaknesses of several complementary Process Analytical Technology (PAT) tools implemented in a continuous wet granulation process, which is part of a fully continuous from powder-to-tablet production line. The use of Raman and NIR-spectroscopy and a particle size distribution analyzer is evaluated for the real-time monitoring of critical parameters during the continuous wet agglomeration of an anhydrous theophylline- lactose blend. The solid state characteristics and particle size of the granules were analyzed in real-time and the critical process parameters influencing these granule characteristics were identified. The temperature of the granulator barrel, the amount of granulation liquid added and, to a lesser extent, the powder feed rate were the parameters influencing the solid state of the active pharmaceutical ingredient (API). A higher barrel temperature and a higher powder feed rate, resulted in larger granules.

Mixing and transport during pharmaceutical twin-screw wet granulation: experimental analysis via chemical imaging.

PubMed

Kumar, Ashish; Vercruysse, Jurgen; Toiviainen, Maunu; Panouillot, Pierre-Emmanuel; Juuti, Mikko; Vanhoorne, Valérie; Vervaet, Chris; Remon, Jean Paul; Gernaey, Krist V; De Beer, Thomas; Nopens, Ingmar

2014-07-01

Twin-screw granulation is a promising continuous alternative for traditional batch high shear wet granulation (HSWG). The extent of HSWG in a twin screw granulator (TSG) is greatly governed by the residence time of the granulation materials in the TSG and degree of mixing. In order to determine the residence time distribution (RTD) and mixing in TSG, mostly visual observation and particle tracking methods are used, which are either inaccurate and difficult for short RTD, or provide an RTD only for a finite number of preferential tracer paths. In this study, near infrared chemical imaging, which is more accurate and provides a complete RTD, was used. The impact of changes in material throughput (10-17 kg/h), screw speed (500-900 rpm), number of kneading discs (2-12) and stagger angle (30-90°) on the RTD and axial mixing of the material was characterised. The experimental RTD curves were used to calculate the mean residence time, mean centred variance and the Péclet number to determine the axial mixing and predominance of convective over dispersive transport. The results showed that screw speed is the most influential parameter in terms of RTD and axial mixing in the TSG and established a significant interaction between screw design parameters (number and stagger angle of kneading discs) and the process parameters (material throughput and number of kneading discs). The results of the study will allow the development and validation of a transport model capable of predicting the RTD and macro-mixing in the TSG. These can later be coupled with a population balance model in order to predict granulation yields in a TSG more accurately. Copyright © 2014 Elsevier B.V. All rights reserved.

Modification of drug release from acetaminophen granules by melt granulation technique - consideration of release kinetics.

PubMed

Uhumwangho, M U; Okor, R S

2006-01-01

Acetaminophen granules have been formed by a melt granulation process with the objective of retarding drug release for prolonged action formulations. The waxes used were goat wax, carnuba wax and glyceryl monostearate. In the melt granulation procedure, acetaminophen powder was triturated with the melted waxes and passed through a sieve of mesh 10 (aperture size 710 microm). The content of wax in resulting granules ranged from 10 to 40%w/w. Acetaminophen granules were also formed by the convectional method of wet granulation with starch mucilage (20%w/w). The granules were subjected to in-vitro drug release tests. The release data were subjected to analysis by three different well-established mathematical models (release kinetics) namely, - zero order flux, first order, and the Higuchi square root of time relationship. The convectional granules exhibited an initial zero order flux (first 55%) followed by a first order release profile (the remaining 45%). The pattern of drug release from the melt granulations was consistent with the first order kinetic and the Higuchi square root of time relationship, indicating a diffusion-controlled release mechanism. The first order release rate constant of the convectional granules was 1.95 +/- 0.02 h(-1). After melt granulation (wax content, 20%w/w) the rate constants dropped drastically to 0.130+/-0.001 h(-1) (goat wax), 0.120+/-0.003 h(-1) (carnuba wax), and 0.130+/-0.002 h(-1) (glyceryl monosterate) indicating that all three waxes were equivalent in retarding drug release from the melt granulations.

Roll Compaction and Tableting of High Loaded Metformin Formulations Using Efficient Binders.

PubMed

Arndt, Oscar-Rupert; Kleinebudde, Peter

2018-04-23

Metformin has a poor tabletability and flowability. Therefore, metformin is typically wet granulated with a binder before tableting. To save production costs, it would be desirable to implement a roll compaction/dry granulation (RCDG) process for metformin instead of using wet granulation. In order to implement RCDG, the efficiency of dry binders is crucial to ensure a high drug load and suitable properties of dry granules and tablets. This study evaluates dry granules manufactured by RCDG and subsequently tableting of high metformin content formulations (≥ 87.5%). Based on previous results, fine particle grades of hydroxypropylcellulose and copovidone in different fractions were compared as dry binders. The formulations are suitable for RCDG and tableting. Furthermore, results can be connected to in-die and out-of-die compressibility analysis. The addition of 7% of dry binder is a good compromise to generate sufficient mechanical properties on the one hand, but also to save resources and ensure a high metformin content on the other hand. Hydroxypropylcellulose was more efficient in terms of granule size, tensile strength and friability. Three percent croscarmellose was added to reach the specifications of the US Pharmacopeia regarding dissolution. The final formulation has a metformin content of 87.5%. A loss in tabletability does not occur for granules compressed at different specific compaction forces, which displays a robust tensile strength of tablets independent of the granulation process.

A novel approach to support formulation design on twin screw wet granulation technology: Understanding the impact of overarching excipient properties on drug product quality attributes.

PubMed

Willecke, N; Szepes, A; Wunderlich, M; Remon, J P; Vervaet, C; De Beer, T

2018-04-21

The overall objective of this work is to understand how excipient characteristics influence the drug product quality attributes and process performance of a continuous twin screw wet granulation process. The knowledge gained in this study is intended to be used for Quality by Design (QbD)-based formulation design and formulation optimization. Three principal components which represent the overarching properties of 8 selected pharmaceutical fillers were used as factors, whereas factors 4 and 5 represented binder type and binder concentration in a design of experiments (DoE). The majority of process parameters were kept constant to minimize their influence on the granule and drug product quality. 27 DoE batches consisting of binary filler/binder mixtures were processed via continuous twin screw wet granulation followed by tablet compression. Multiple linear regression models were built providing understanding of the impact of filler and binder properties on granule and tablet quality attributes (i.e. 16 DoE responses). The impact of fillers on the granule and tablet responses was more dominant compared to the impact of binder type and concentration. The filler properties had a relevant effect on granule characteristics, such as particle size, friability and specific surface area. Binder type and concentration revealed a relevant influence on granule flowability and friability as well as on the compactability (required compression force during tableting to obtain target hardness). In order to evaluate the DoE models' validity, a verification of the DoE models was performed with new formulations (i.e. a new combination of filler, binder type and binder concentration) which were initially not included in the dataset used to build the DoE models. The combined PCA (principle component analysis)/DoE approach allowed to link the excipient properties with the drug product quality attributes. Copyright © 2018 Elsevier B.V. All rights reserved.

Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.

PubMed

Vercruysse, Jurgen; Toiviainen, Maunu; Fonteyne, Margot; Helkimo, Niko; Ketolainen, Jarkko; Juuti, Mikko; Delaet, Urbain; Van Assche, Ivo; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

2014-04-01

Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system. Copyright © 2013 Elsevier B.V. All rights reserved.

Formulation and evaluation of dried yeast tablets using different techniques.

PubMed

Al-Mohizea, Abdullah M; Ahmed, Mahrous O; Al-jenoobi, Fahad I; Mahrous, Gamal M; Abdel-Rahman, Aly A

2007-08-01

The aim of this study was to prepare and evaluate dried yeast tablets using both direct compression and dry granulation techniques in comparison with the conventional wet granulation as well as commercial product. Wet granulation technique is not favorable for producing the yeast tablets due to the problems of color darkening and the reduction of the fermentation power of the yeast as a result of the early start of the fermentation process due to the presence of moisture. Twenty six formulae of dried yeast tablets were prepared and evaluated. Certain directly compressible vehicles were employed for preparing these tablets. The quality control tests (weight uniformity, friability, disintegration time and hardness) of the prepared dried yeast tablets were performed according to B.P. 1998 limits. All batches of the prepared tablets complied with the B.P. limits of weight uniformity. Moreover, small values of friability % (1% or less) were obtained for all batches of dried yeast tablets with acceptable hardness values, indicating good mechanical properties which can withstand handling. On the other hand, not all batches complied with the limit of disintegration test which may be attributed to various formulation component variables. Therefore, four disintegrating agents were investigated for their disintegrating effect. It was found that the method of preparation, whether it is direct compression, dry granulation or wet granulation, has an effect on disintegration time of these dried yeast tablets and short disintegration times were obtained for some of the formulae. The shortest disintegration time was obtained with those tablets prepared by direct compression among the other techniques. Therefore, the direct compression is considered the best technique for preparation of dried yeast tablets and the best formula (which showed shorter disintegration time and better organoleptic properties than the available commercial yeast tablets) was chosen. Drug content for dried yeast granular powder, and the chosen best prepared formula, was determined by gas chromatography (GC). It was found that this formula gave the same alcohol content produced by an equal amount of the dried yeast granular powder. This result in conjunction with weight uniformity indicated drug content uniformity of the prepared dried yeast tablets.

Improved tabletability after a polymorphic transition of delta-mannitol during twin screw granulation.

PubMed

Vanhoorne, V; Bekaert, B; Peeters, E; De Beer, T; Remon, J-P; Vervaet, C

2016-06-15

In most formulations processed via continuous twin screw granulation microcrystalline cellulose (MCC) and/or lactose are used as excipients, but mannitol is also a preferred excipient for wet granulation and tableting due to its non-hygroscopicity and inertness. Therefore, the aim of the current study was to investigate the influence of process parameters on critical quality attributes of granules (moisture content, solid state, morphology, size distribution, specific surface area, friability, flowability and hygroscopicity) and tablets (tensile strength and friability) after twin screw granulation of δ-mannitol. The δ-polymorph was selected since a moisture-induced transformation to β-mannitol was observed during batch wet granulation, which exhibited a unique morphology with a large surface area and improved tabletability. A full factorial experimental design was performed, varying screw speed (400-900rpm), granulation temperature (25-40°C), number of kneading elements (6 or 12) and liquid-to-solid (L/S) ratio, on the granulation unit of a ConsiGma™-25 line (a continuous powder-to-tablet manufacturing system). After tray drying the granules were milled and tableted. The results showed that the polymorphic transition from δ- to β-mannitol also occurred during twin screw granulation, although the residence time and L/S ratios were much lower in continuous twin screw granulation compared to batch processing. However, the polymorphic transition was not complete in all experiments and depended on the L/S ratio, screw speed and number of kneading elements. Nevertheless all granules exhibited the unique morphology linked to the polymorphic transition and had a superior tabletability compared to granules produced with β-mannitol as starting material. This was attributed to enhanced plastic deformation of the granules manufactured using δ-mannitol as starting material. In addition, it was concluded that mannitol was granulated via a different mechanism than other, less-soluble, excipients (e.g. lactose, microcrystalline cellulose) due to its high solubility and dissolution rate as the influence of process parameters on the mannitol granule characteristics was different. Copyright © 2016 Elsevier B.V. All rights reserved.

Elucidation of solution state complexation in wet-granulated oven-dried ibuprofen and beta-cyclodextrin: FT-IR and 1H-NMR studies.

PubMed

Ghorab, M K; Adeyeye, M C

2001-08-01

The effect of oven-dried wet granulation on the complexation of beta-cyclodextrin with ibuprofen (IBU) in solution was investigated using Fourier transform infrared spectroscopy (FT-IR), proton nuclear magnetic resonance (1H NMR), and molecular modeling. Granulation was carried out using 5 mL of three different granulating solvents; water, ethanol (95% v/v), and isopropanol and the granules were oven-dried at 60 degrees C for 2 h. The granules were compared to oven-dried physical mixture and conventionally prepared complex. Phase solubility study was performed to investigate the stability of the granulation-formed complexes in solution. FT-IR was used to examine the complexation in the granules while 1H NMR, and molecular modeling studies were carried out to determine the mechanism of complexation in the water-prepared granules. The solubility studies suggested a 1:1 complex between IBU and betaCD. It also showed that the stability of the complex in solution was in the following order with respect to the granulating solvents: ethanol > water > isopropanol. The FT-IR study revealed a shift in the carboxylic acid stretching band and decrease in the intensities of the C-H bending bands of the isopropyl group and the out-of-plane aromatic ring, of IBU, in granules compared to the oven-dried physical mixture. This indicated that granules might have some extent of solid state complexation that could further enhance dissolution and the IBU-betaCD solution state complexation. 1H NMR showed that water prepared oven-dried granules had a different 1H NMR spectrum compared to similarly made oven-dried physical mixture, indicative of complexation in the former. The 1H NMR and the molecular modeling studies together revealed that solution state complexation from the granules occurred by inclusion of the isopropyl group together with part of the aromatic ring of IBU into the betaCD cavity probably through its wider side. These results indicate that granulation process induced faster complexation in solution which enhances the solubility and the dissolution rate of poorly soluble drugs. The extent of complexation in the granules was dependent on the type of solvent used.

Formulation design and optimization of mouth dissolve tablets of nimesulide using vacuum drying technique.

PubMed

Gohel, Mukesh; Patel, Madhabhai; Amin, Avani; Agrawal, Ruchi; Dave, Rikita; Bariya, Nehal

2004-04-26

The purpose of this research was to develop mouth dissolve tablets of nimesulide. Granules containing nimesulide, camphor, crospovidone, and lactose were prepared by wet granulation technique. Camphor was sublimed from the dried granules by exposure to vacuum. The porous granules were then compressed. Alternatively, tablets were first prepared and later exposed to vacuum. The tablets were evaluated for percentage friability, wetting time, and disintegration time. In the investigation, a 32 full factorial design was used to investigate the joint influence of 2 formulation variables: amount of camphor and crospovidone. The results of multiple linear regression analysis revealed that for obtaining a rapidly disintegrating dosage form, tablets should be prepared using an optimum concentration of camphor and a higher percentage of crospovidone. A contour plot is also presented to graphically represent the effect of the independent variables on the disintegration time and percentage friability. A checkpoint batch was also prepared to prove the validity of the evolved mathematical model. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The systematic formulation approach helped in understanding the effect of formulation processing variables.

Attenuated Total Reflection Fourier Transform Infrared (ATR FT-IR) Spectroscopy as an Analytical Method to Investigate the Secondary Structure of a Model Protein Embedded in Solid Lipid Matrices.

PubMed

Zeeshan, Farrukh; Tabbassum, Misbah; Jorgensen, Lene; Medlicott, Natalie J

2018-02-01

Protein drugs may encounter conformational perturbations during the formulation processing of lipid-based solid dosage forms. In aqueous protein solutions, attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy can investigate these conformational changes following the subtraction of spectral interference of solvent with protein amide I bands. However, in solid dosage forms, the possible spectral contribution of lipid carriers to protein amide I band may be an obstacle to determine conformational alterations. The objective of this study was to develop an ATR FT-IR spectroscopic method for the analysis of protein secondary structure embedded in solid lipid matrices. Bovine serum albumin (BSA) was chosen as a model protein, while Precirol AT05 (glycerol palmitostearate, melting point 58 ℃) was employed as the model lipid matrix. Bovine serum albumin was incorporated into lipid using physical mixing, melting and mixing, or wet granulation mixing methods. Attenuated total reflection FT-IR spectroscopy and size exclusion chromatography (SEC) were performed for the analysis of BSA secondary structure and its dissolution in aqueous media, respectively. The results showed significant interference of Precirol ATO5 with BSA amide I band which was subtracted up to 90% w/w lipid content to analyze BSA secondary structure. In addition, ATR FT-IR spectroscopy also detected thermally denatured BSA solid alone and in the presence of lipid matrix indicating its suitability for the detection of denatured protein solids in lipid matrices. Despite being in the solid state, conformational changes occurred to BSA upon incorporation into solid lipid matrices. However, the extent of these conformational alterations was found to be dependent on the mixing method employed as indicated by area overlap calculations. For instance, the melting and mixing method imparted negligible effect on BSA secondary structure, whereas the wet granulation mixing method promoted more changes. Size exclusion chromatography analysis depicted the complete dissolution of BSA in the aqueous media employed in the wet granulation method. In conclusion, an ATR FT-IR spectroscopic method was successfully developed to investigate BSA secondary structure in solid lipid matrices following the subtraction of lipid spectral interference. The ATR FT-IR spectroscopy could further be applied to investigate the secondary structure perturbations of therapeutic proteins during their formulation development.

40 CFR 180.510 - Pyriproxyfen; tolerances for residues.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Apple, wet pomace 0.8 Artichoke, globe 2.0 Asparagus 2.0 Atemoya 0.20 Avocado 1.0 Banana 0.20 Beet..., granules/flakes 0.75 Potato, wet peel 0.75 Pulasan 0.30 Rambutan 0.30 Rice, hulls 5.5 Safflower, seed 0.20...

40 CFR 180.510 - Pyriproxyfen; tolerances for residues.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Apple, wet pomace 0.8 Artichoke, globe 2.0 Asparagus 2.0 Atemoya 0.20 Avocado 1.0 Banana 0.20 Beet..., granules/flakes 0.75 Potato, wet peel 0.75 Pulasan 0.30 Rambutan 0.30 Rice, hulls 5.5 Safflower, seed 0.20...

40 CFR 180.510 - Pyriproxyfen; tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Apple, wet pomace 0.8 Artichoke, globe 2.0 Asparagus 2.0 Atemoya 0.20 Avocado 1.0 Banana 0.20 Beet..., granules/flakes 0.75 Potato, wet peel 0.75 Pulasan 0.30 Rambutan 0.30 Rice, hulls 5.5 Safflower, seed 0.20...

Real-time feedback control of twin-screw wet granulation based on image analysis.

PubMed

Madarász, Lajos; Nagy, Zsombor Kristóf; Hoffer, István; Szabó, Barnabás; Csontos, István; Pataki, Hajnalka; Démuth, Balázs; Szabó, Bence; Csorba, Kristóf; Marosi, György

2018-06-04

The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored by a process camera coupled with an image analysis software developed by the authors. The validation of the developed system showed that the particle size analysis tool can determine the size of the granules with an error of less than 5 µm. The next step was to implement real-time feedback control of the process by controlling the liquid feeding rate of the pump through a PC, based on the real-time determined particle size results. After the establishment of the feedback control, the system could correct different real-life disturbances, creating a Process Analytically Controlled Technology (PACT), which guarantees the real-time monitoring and controlling of the quality of the granules. In the event of changes or bad tendencies in the particle size, the system can automatically compensate the effect of disturbances, ensuring proper product quality. This kind of quality assurance approach is especially important in the case of continuous pharmaceutical technologies. Copyright © 2018 Elsevier B.V. All rights reserved.

Roller compaction of hydrophilic extended release tablets-combined effects of processing variables and drug/matrix former particle size.

PubMed

Heiman, Johanna; Tajarobi, Farhad; Gururajan, Bindhumadhavan; Juppo, Anne; Abrahmsén-Alami, Susanna

2015-04-01

The present study shows that roller compaction (RC) can successfully be used as a granulation method to prepare hydroxypropyl methylcellulose (HPMC)-based extended release matrix tablets containing a high drug load, both for materials deforming mainly by fragmentation (paracetamol) as for those having mainly plastic deformation (ibuprofen). The combined effect of RC process variables and composition on the manufacturability of HPMC tablets was investigated. Standard wet granulation grade HPMC was compared with a larger particle size direct compressible HPMC grade. Higher roll pressure was found to result in larger paracetamol granules and narrower granule particle size distributions, especially for formulations containing smaller size HPMC. However, for ibuprofen, no clear effect of roll pressure was observed. High roll pressure also resulted in denser ribbon and less bypass fines during RC. Loss of compactibility was observed for granules compared to powder blends, which was found to be related to differences in granule porosity and morphology. Using the large-sized HPMC grade did in some cases result in lower tensile strength tablets but had the advantage to improve the powder flow into the roller compactor. This work also indicates that when the HPMC level lies near the percolation threshold, significant changes can occur in the drug release rate due to changes in other factors (raw material characteristics and processing).

Layered growth with bottom-spray granulation for spray deposition of drug.

PubMed

Er, Dawn Z L; Liew, Celine V; Heng, Paul W S

2009-07-30

The gap in scientific knowledge on bottom-spray fluidized bed granulation has emphasized the need for more studies in this area. This paper comparatively studied the applicability of a modified bottom-spray process and the conventional top-spray process for the spray deposition of a micronized drug during granulation. The differences in circulation pattern, mode of growth and resultant granule properties between the two processes were highlighted. The more ordered and consistent circulation pattern of particles in a bottom-spray fluidized bed was observed to give rise to layered granule growth. This resulted in better drug content uniformity among the granule batches and within a granule batch. The processes' sensitivities to wetting and feed material characteristics were also compared and found to differ markedly. Less robustness to differing process conditions was observed for the top-spray process. The resultant bottom-spray granules formed were observed to be less porous, more spherical and had good flow properties. The bottom-spray technique can thus be potentially applied for the spray deposition of drug during granulation and was observed to be a good alternative to the conventional technique for preparing granules.

[Influence of polymer type on the physical properties and the release study of papaverine hydrochloride from tablets].

PubMed

Kasperek, Regina; Polski, Andrzej; Sobótka-Polska, Karolina; Poleszak, Ewa

2014-01-01

Polymers are widely used in drug manufacturing. Researchers studied their impact on the bioavailability of active substances or on physical properties of tablets for many years. To study the influence of polymer excipients, such as microcrystalline cellulose (Avicel PH 101, Avicel PH 102), croscarmellose sodium, crospovidone or polyvinylpyrrolidone, on the release profile of papaverine hydrochloride from tablets and on the physical properties of tablets. Six series of uncoated tablets were prepared by indirect method, with previous wet granulation. Tablets contained papaverine hydrochloride and various excipients. The physical properties of the prepared granules, tablets and the release profile of papaverine hydrochloride from tablets were examined. The content of papaverine hydrochloride from the release study were determined spectrophotometrically. All tablets met the pharmacopoeia requirements during following tests: the disintegration time of tablets, uncoated tablets resistance to abrasion, the weight uniformity and dose formulations, their dimensions, the resistance to crushing of tablets and the drug substance content in the tablet. In four cases more than 80% of papaverine was released up to 2 min, in one formula it was up to 5 min, and in last one up to 10 min. Tablets containing crospovidone disintegrated faster than tablets with croscarmellose sodium. Adding gelatinized starch to the tablet composition increased the disintegration time, hardness and delayed the release of papaverine. During the wet granulation process, granules containing polyvinylpyrrolidone were characterized by a suitable flow properties and slightly prolonged disintegration time. Tablets containing Avicel PH 102 compared to tablets with Avicel PH 101 had less weight loss during the test of mechanical resistance, improved hardness and faster release profile of papaverine from tablets.

Metatranscriptomic and metagenomic description of the bacterial nitrogen metabolism in waste water wet oxidation effluents.

PubMed

Crovadore, Julien; Soljan, Vice; Calmin, Gautier; Chablais, Romain; Cochard, Bastien; Lefort, François

2017-10-01

Anaerobic digestion is a common method for reducing the amount of sludge solids in used waters and enabling biogas production. The wet oxidation process (WOX) improves anaerobic digestion by converting carbon into methane through oxidation of organic compounds. WOX produces effluents rich in ammonia, which must be removed to maintain the activity of methanogens. Ammonia removal from WOX could be biologically operated by aerobic granules. To this end, granulation experiments were conducted in 2 bioreactors containing an activated sludge (AS). For the first time, the dynamics of the microbial community structure and the expression levels of 7 enzymes of the nitrogen metabolism in such active microbial communities were followed in regard to time by metagenomics and metatranscriptomics. It was shown that bacterial communities adapt to the wet oxidation effluent by increasing the expression level of the nitrogen metabolism, suggesting that these biological activities could be a less costly alternative for the elimination of ammonia, resulting in a reduction of the use of chemicals and energy consumption in sewage plants. This study reached a strong sequencing depth (from 4.4 to 7.6 Gb) and enlightened a yet unknown diversity of the microorganisms involved in the nitrogen pathway. Moreover, this approach revealed the abundance and expression levels of specialised enzymes involved in nitrification, denitrification, ammonification, dissimilatory nitrate reduction to ammonium (DNRA) and nitrogen fixation processes in AS.

Trace element distribution in the rat cerebellum

NASA Astrophysics Data System (ADS)

Kwiatek, W. M.; Long, G. J.; Pounds, J. G.; Reuhl, K. R.; Hanson, A. L.; Jones, K. W.

1990-04-01

Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic and structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with X-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and nondestructive irradiation. Trace elements were measured in thin rat brain sections of 20 μm thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppm wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semiquantitative mapping of the TE distribution in a section were used. All analyzed elements were observed in each structure of the cerebellum except mercury which was not observed in granule cell layer or fiber tract. This approach permits an exacting correlation of the TE distribution in complex structure with the diet, toxic elements, and functional status of the animal.

Fabrication and physicochemical characterization of porous composite microgranules with selenium oxyanions and risedronate sodium for potential applications in bone tumors.

PubMed

Kolmas, Joanna; Pajor, Kamil; Pajchel, Lukasz; Przekora, Agata; Ginalska, Grażyna; Oledzka, Ewa; Sobczak, Marcin

2017-01-01

Nanocrystalline hydroxyapatite containing selenite ions (SeHA; 9.6 wt.% of selenium) was synthesized using wet method and subject to careful physicochemical analysis by powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, solid-state nuclear magnetic resonance, wavelength dispersive X-ray fluorescence, and inductively coupled plasma optical emission spectrometry. SeHA was then used to develop the selenium-containing hydroxyapatite/alginate (SeHA/ALG) composite granules. Risedronate sodium (RIS) was introduced to the obtained spherical microgranules of a size of about 1.1-1.5 mm in 2 ways: during the granules' preparation (RIS solution added to a suspension of ALG and SeHA), and as a result of SeHA/ALG granules soaking in aqueous RIS solution. The analysis made using 13 C and 31 P cross-polarization magic angle spinning nuclear magnetic resonance confirmed the presence of RIS and its interaction with calcium ions. Then, the release of selenium (inductively coupled plasma optical emission spectrometry) and RIS (high-performance liquid chromatography) from microgranules was examined. Moreover, cytotoxicity of fabricated granules was assessed by MTT test. Selenium release was biphasic: the first stage was short and ascribed to a "burst release" probably from a hydrated surface layer of SeHA crystals, while the next stage was significantly longer and ascribed to a sustained release of selenium from the crystals' interior. The study showed that the method of obtaining microgranules containing RIS significantly affects its release profile. Performed cytotoxicity test revealed that fabricated granules had high antitumor activity against osteosarcoma cells. However, because of the "burst release" of selenium during the first 10 h, the granules significantly reduced viability of normal osteoblasts as well.

Pharmaceutical and analytical evaluation of triphalaguggulkalpa tablets

PubMed Central

Savarikar, Shreeram S.; Barbhind, Maneesha M.; Halde, Umakant K.; Kulkarni, Alpana P.

2011-01-01

Aim of the Study: Development of standardized, synergistic, safe and effective traditional herbal formulations with robust scientific evidence can offer faster and more economical alternatives for the treatment of disease. The main objective was to develop a method of preparation of guggulkalpa tablets so that the tablets meet the criteria of efficacy, stability, and safety. Materials and Methods: Triphalaguggulkalpa tablet, described in sharangdharsanhita and containing guggul and triphala powder, was used as a model drug. Preliminary experiments on marketed triphalaguggulkalpa tablets exhibited delayed in vitro disintegration that indicated probable delayed in vivo disintegration. The study involved preparation of triphalaguggulkalpa tablets by Ayurvedic text methods and by wet granulation, dry granulation, and direct compression method. The tablets were evaluated for loss on drying, volatile oil content, % solubility, and steroidal content. The tablets were evaluated for performance tests like weight variation, disintegration, and hardness. Results: It was observed that triphalaguggulkalpa tablets, prepared by direct compression method, complied with the hardness and disintegration tests, whereas tablets prepared by Ayurvedic text methods failed. Conclusion: Direct compression is the best method of preparing triphalaguggulkalpa tablets. PMID:21731383

In vitro and in vivo evaluation of medicinal carbon granules and tablet on the adsorption of acetaminophen.

PubMed

Yamamoto, Kenta; Onishi, Hiraku; Ito, Akihiko; Machida, Yoshiharu

2007-01-10

Medicinal carbon (MC) granules were prepared by wet granulation using maltitol (MT), and the MC tablet was produced by compression of the granules. The physical properties and the in vitro adsorption capacity for AA of the formulations were examined. Further, the effects of MC alone and the granules on gastrointestinal absorption of AA were examined in rats when they were administered intragastrically at 15 or 45 min after the intragastrical administration of AA. AA was rapidly adsorbed by MC, and the maximum adsorption capacity of MC was 0.329g AA per gram MC. The granules and tablet exhibited adequate strength, and the tablet disintegrated rapidly. The granules and tablet showed similar adsorption profiles, but somewhat lower adsorption capacity than MC alone. MC alone and granules administered at 15 min reduced the AUC(0-infinity) significantly against the control (no treatment); however, the suppression effect on the plasma concentration was lower with the granules than with MC alone. Thus, granules and tablet are useful as a compact dosage form of MC; though the reduced adsorption capacity must be taken into account in order to expect efficacy equivalent to that of MC alone.

Investigation of the effect of impeller speed on granules formed using a PMA-1 high shear granulator.

PubMed

Logan, R; Briens, L

2012-11-01

Impeller speed was varied from 300 to 1500 rpm during the wet high shear granulation of a placebo formulation using a new vertical shaft PharmaMATRIX-1 granulator. The resulting granules were extensively analysed for differences caused by the varying impeller speed with emphasis on flowability. Microscopy showed that initial granules were formed primarily from microcrystalline cellulose at all tested impeller speeds. At low impeller speed of 300 rpm in the "bumpy" flow regime, forces from the impeller were insufficient to incorporate all the components of the formulation into the granules and to promote granule growth to a size that significantly improved flowability. The "roping" flow regime at higher impeller speeds promoted granule growth to a median particle size of at least 100 µm that improved the flowability of the mixture. Particle size distribution measurements and advanced indicators based on avalanching behavior, however, showed that an impeller speed of 700 rpm produced the largest fraction of optimal granules with the best flowability potential. This impeller speed allowed good development of "roping" flow for sufficient mixing, collision rates and kinetic energy for collisions while minimizing excessive centrifugal forces that promote buildup around the bowl perimeter.

Latent structure analysis of the process variables and pharmaceutical responses of an orally disintegrating tablet.

PubMed

Hayashi, Yoshihiro; Oshima, Etsuko; Maeda, Jin; Onuki, Yoshinori; Obata, Yasuko; Takayama, Kozo

2012-01-01

A multivariate statistical technique was applied to the design of an orally disintegrating tablet and to clarify the causal correlation among variables of the manufacturing process and pharmaceutical responses. Orally disintegrating tablets (ODTs) composed mainly of mannitol were prepared via the wet-granulation method using crystal transition from the δ to the β form of mannitol. Process parameters (water amounts (X(1)), kneading time (X(2)), compression force (X(3)), and amounts of magnesium stearate (X(4))) were optimized using a nonlinear response surface method (RSM) incorporating a thin plate spline interpolation (RSM-S). The results of a verification study revealed that the experimental responses, such as tensile strength and disintegration time, coincided well with the predictions. A latent structure analysis of the pharmaceutical formulations of the tablet performed using a Bayesian network led to the clear visualization of a causal connection among variables of the manufacturing process and tablet characteristics. The quantity of β-mannitol in the granules (Q(β)) was affected by X(2) and influenced all granule properties. The specific surface area of the granules was affected by X(1) and Q(β) and had an effect on all tablet characteristics. Moreover, the causal relationships among the variables were clarified by inferring conditional probability distributions. These techniques provide a better understanding of the complicated latent structure among variables of the manufacturing process and tablet characteristics.

76 FR 5696 - Fluazifop-P-butyl; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-02

... for residues of the herbicide, fluazifop-P- butyl, in or on banana and plantains at 0.01 parts per..., peel (wet) at 1.1 ppm; potato, chips at 3.0 ppm; and potato, granules/flakes at 5.0 ppm. That notice... determined that the proposed tolerances for plantains, sugarbeet (top), and potato peel (wet) are unnecessary...

Improving Powder Tableting Performance through Materials Engineering

NASA Astrophysics Data System (ADS)

Osei-Yeboah, Frederick

Adequate mechanical strength is a critical requirement to the successful development of a tablet product. Before tablet compression, powders are often engineered by various processes including wet granulation and surface coating, which may improve or adversely affect the powder tableting performance. Such effects, commonly, result from a change in either particle mechanical properties or particulate (size, shape) properties. In this work, tableting performance is interpreted based on the qualitative bonding-area and bonding-strength (BABS) model. The tabletability of the microcrystalline cellulose (MCC) granules deteriorates rapidly with increasing amount of granulating water and eventually leads to over-granulation at high water level. Granule surface smoothing, size enlargement, granule densification and shape rounding are the dominant factors leading to the tabletability reduction of plastic MCC. Incorporation of increasing amounts of brittle excipients, such as lactose or dibasic calcium phosphate reduces the rate of tabletability reduction by promoting more granule fragmentation, introducing more surface area available for bonding. When a sufficient amount of brittle excipients is used, the over-granulation phenomenon can be eliminated. Surface coating of incompressible MCC pellets with highly bonding polymer leads to sufficient surface deformation and adhesion to enable direct compression of the pellets into tablets of adequate mechanical strength. This improvement is enhanced by the presence of moisture, which plasticizes the polymer to allow the development of a larger bonding area between coated pellets. The relationship between mechanical properties and tableting behavior is systematically investigated in polymeric composites using celecoxib-polyvinylpyrrolidone vinyl acetate solid dispersions. Mechanical properties such as indentation hardness of the solid dispersions were measured using nanoindentation. Incorporation of celecoxib up to 60% by weight hardens the polymers, which reduces bonding area but increases bonding strength. On the other hand, moisture softens the solid dispersions and facilitates deformation under pressure to improve tablet mechanical strength. In summary, insights into the deteriorated tabletability of wet granulated powders have been developed and strategies for improving tabletability have been demonstrated. Also, the relationship between particle mechanical properties and tableting performance has been examined using solid dispersions. The BABS model has been further developed to enable its widespread application in interpreting complex tableting behavior.

Impact of formulation and process variables on solid-state stability of theophylline in controlled release formulations.

PubMed

Korang-Yeboah, Maxwell; Rahman, Ziyaur; Shah, Dhaval; Mohammad, Adil; Wu, Suyang; Siddiqui, Akhtar; Khan, Mansoor A

2016-02-29

Understanding the impact of pharmaceutical processing, formulation excipients and their interactions on the solid-state transitions of pharmaceutical solids during use and in storage is critical in ensuring consistent product performance. This study reports the effect of polymer viscosity, diluent type, granulation and granulating fluid (water and isopropanol) on the pseudopolymorphic transition of theophylline anhydrous (THA) in controlled release formulations as well as the implications of this transition on critical quality attributes of the tablets. Accordingly, 12 formulations were prepared using a full factorial screening design and monitored over a 3 month period at 40 °C and 75%. Physicochemical characterization revealed a drastic drop in tablet hardness accompanied by a very significant increase in moisture content and swelling of all formulations. Spectroscopic analysis (ssNMR, Raman, NIR and PXRD) indicated conversion of THA to theophylline monohydrate (TMO) in all formulations prepared by aqueous wet granulation in as early as two weeks. Although all freshly prepared formulations contained THA, the hydration-dehydration process induced during aqueous wet granulation hastened the pseudopolymorphic conversion of theophylline during storage through a cascade of events. On the other hand, no solid state transformation was observed in directly compressed formulations and formulations in which isopropanol was employed as a granulating fluid even after the twelve weeks study period. The transition of THA to TMO resulted in a decrease in dissolution while an increase in dissolution was observed in directly compressed and IPA granulated formulation. Consequently, the impact of pseudopolymorphic transition of theophylline on dissolution in controlled release formulations may be the net result of two opposing factors: swelling and softening of the tablets which tend to favor an increase in drug dissolution and hydration of theophylline which decreases the drug dissolution. Published by Elsevier B.V.

Shear Resistance Variations in Experimentally Sheared Mudstone Granules: A Possible Shear-Thinning and Thixotropic Mechanism

NASA Astrophysics Data System (ADS)

Hu, Wei; Xu, Qiang; Wang, Gonghui; Scaringi, Gianvito; Mcsaveney, Mauri; Hicher, Pierre-Yves

2017-11-01

We present results of ring shear frictional resistance for mudstone granules of different size obtained from a landslide shear zone. Little rate dependency of shear resistance was observed in sand-sized granules in any wet or dry test, while saturated gravel-sized granules exhibited significant and abrupt reversible rate-weakening (from μ = 0.6 to 0.05) at about 2 mm/s. Repeating resistance variations occurred also under constant shear displacement rate. Mudstone granules generate mud as they are crushed and softened. Shear-thinning and thixotropic behavior of the mud can explain the observed behavior: with the viscosity decreasing, the mud can flow through the coarser soil pores and migrate out from the shear zone. This brings new granules into contact which produces new mud. Thus, the process can start over. Similarities between experimental shear zones and those of some landslides in mudstone suggest that the observed behavior may play a role in some landslide kinematics.

Influence of metronidazole particle properties on granules prepared in a high-shear mixer-granulator.

PubMed

Di Martino, Piera; Censi, Roberta; Malaj, Ledjan; Martelli, Sante; Joiris, Etienne; Barthélémy, Christine

2007-02-01

Metronidazole is a good example of high-dose drug substance with poor granulating and tableting properties. Tablets are generally produced by liquid granulation; however, the technological process failure is quite frequent. In order to verify how the metronidazole particle characteristics can influence granule properties, three metronidazole batches differing for crystal habit, mean particle size, BET surface area and wettability were selected, primarily designed according to their different elongation ratio: needle-shaped, stick-shaped, and isodimensional. In the presence of lactose monohydrate and pregelatinized maize starch, respectively as diluent and binder, they were included in a formula for wet granulation in a high-shear mixer-granulator. In order to render the process comparable as far as possible, all parameters and experimental conditions were maintained constant. Four granule batches were obtained: granules from placebo (G-placebo), granules from needle-shaped crystals (G-needle-shaped), granules from stick-shaped crystals (G-stick-shaped), and granules from isodimensional crystals (G-isodimensional). Different granule properties were considered, in particular concerning porosity, friability, loss on drying (LOD), and flowability. In order to study their tabletability and compressibility, the different granules obtained were then compressed in a rotary press. The best tabletability was obtained with the isodimensional batch, while the poorest was exhibited by the stick-shaped one. Differences in tabletability are in good accordance with compressibility results: to a better tabletability corresponds an important granule ability to undergo a volume reduction as a result of an applied pressure. In particular, it was proposed that the greatest compressibility of the G-isodimensional must be related to the greatest granule porosity percentage.

Mechanistic understanding of the link between Sodium Starch Glycolate properties and the performance of tablets made by wet granulation.

PubMed

Wren, S A C; Alhusban, F; Barry, A R; Hughes, L P

2017-08-30

The impact of varying Sodium Starch Glycolate (SSG) grade and wet granulation intensity on the mechanism of disintegration and dissolution of mannitol-based Immediate Release (IR) placebo tablets was investigated. MRI and 1 H NMR provided mechanistic insight, and revealed a four-fold range in both tablet disintegration and dissolution rates. MRI was used to quantify the rates of change in tablet volumes and the data fitted to a hydration/erosion model. Reduced levels of cross-linking change SSG from a swelling to a gelling matrix. The tablet hydration and dissolution rates are related to the viscosity at the tablet-solution interface, with high viscosities limiting mass transport. Copyright © 2017 Elsevier B.V. All rights reserved.

Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets.

PubMed

Fonteyne, Margot; Wickström, Henrika; Peeters, Elisabeth; Vercruysse, Jurgen; Ehlers, Henrik; Peters, Björn-Hendrik; Remon, Jean Paul; Vervaet, Chris; Ketolainen, Jarkko; Sandler, Niklas; Rantanen, Jukka; Naelapää, Kaisa; De Beer, Thomas

2014-07-01

Continuous manufacturing gains more and more interest within the pharmaceutical industry. The International Conference of Harmonisation (ICH) states in its Q8 'Pharmaceutical Development' guideline that the manufacturer of pharmaceuticals should have an enhanced knowledge of the product performance over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect their processability and several critical quality attributes of the resulting granules and tablets. Copyright © 2014 Elsevier B.V. All rights reserved.

Evaluation of the wound-healing activity of Hibiscus rosa sinensis L (Malvaceae) in Wistar albino rats

PubMed Central

Bhaskar, Anusha; Nithya, V.

2012-01-01

Objective: To investigate the wound-healing potency of the ethanolic extract of the flowers of Hibiscus rosa sinensis. Materials and Methods: The wound-healing activity of H. rosa sinensis (5 and 10% w/w) on Wistar albino rats was studied using three different models viz., excision, incision and dead space wound. The parameters studied were breaking strength in incision model, granulation tissue dry weight, breaking strength and collagen content in dead space wound model, percentage of wound contraction and period of epithelization in excision wound model. The granulation tissue formed on days 4, 8, 12, and 16 (post-wound) was used to estimate total collagen, hexosamine, protein, DNA and uronic acid. Data were analyzed by Analysis of Variance (ANOVA) test. P<0.05 was considered statistically significant. Results: The extract increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and total collagen content of granulation tissues. The extract-treated wounds were found to heal much faster as indicated by improved rates of epithelialization and wound contraction. The extract of H. rosa sinensis significantly (P<0.001) increased the wound-breaking strength in the incision wound model compared to controls. The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly (P<0.001) increased as compared to control wounds. Wet and dry granulation tissue weights in a dead space wound model increased significantly (P<0.001). There was a significant increase in wound closure rate, tensile strength, dry granuloma weight, wet granuloma weight and decrease in epithelization period in H. rosa sinensis-treated group as compared to control and standard drug-treated groups. Conclusion: The ethanolic extract of H. rosa sinensis had greater wound-healing activity than the nitrofurazone ointment. PMID:23248396

Fabrication and physicochemical characterization of porous composite microgranules with selenium oxyanions and risedronate sodium for potential applications in bone tumors

PubMed Central

Kolmas, Joanna; Pajor, Kamil; Pajchel, Lukasz; Przekora, Agata; Ginalska, Grażyna; Oledzka, Ewa; Sobczak, Marcin

2017-01-01

Nanocrystalline hydroxyapatite containing selenite ions (SeHA; 9.6 wt.% of selenium) was synthesized using wet method and subject to careful physicochemical analysis by powder X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, solid-state nuclear magnetic resonance, wavelength dispersive X-ray fluorescence, and inductively coupled plasma optical emission spectrometry. SeHA was then used to develop the selenium-containing hydroxyapatite/alginate (SeHA/ALG) composite granules. Risedronate sodium (RIS) was introduced to the obtained spherical microgranules of a size of about 1.1–1.5 mm in 2 ways: during the granules’ preparation (RIS solution added to a suspension of ALG and SeHA), and as a result of SeHA/ALG granules soaking in aqueous RIS solution. The analysis made using 13C and 31P cross-polarization magic angle spinning nuclear magnetic resonance confirmed the presence of RIS and its interaction with calcium ions. Then, the release of selenium (inductively coupled plasma optical emission spectrometry) and RIS (high-performance liquid chromatography) from microgranules was examined. Moreover, cytotoxicity of fabricated granules was assessed by MTT test. Selenium release was biphasic: the first stage was short and ascribed to a “burst release” probably from a hydrated surface layer of SeHA crystals, while the next stage was significantly longer and ascribed to a sustained release of selenium from the crystals’ interior. The study showed that the method of obtaining microgranules containing RIS significantly affects its release profile. Performed cytotoxicity test revealed that fabricated granules had high antitumor activity against osteosarcoma cells. However, because of the “burst release” of selenium during the first 10 h, the granules significantly reduced viability of normal osteoblasts as well. PMID:28848343

Process for treating moisture laden coal fines

DOEpatents

Davis, Burl E.; Henry, Raymond M.; Trivett, Gordon S.; Albaugh, Edgar W.

1993-01-01

A process is provided for making a free flowing granular product from moisture laden caked coal fines, such as wet cake, by mixing a water immiscible substance, such as oil, with the caked coal, preferably under low shear forces for a period of time sufficient to produce a plurality of free flowing granules. Each granule is preferably comprised of a dry appearing admixture of one or more coal particle, 2-50% by weight water and the water immiscible substance.

Rapid quantitation of atorvastatin in process pharmaceutical powder sample using Raman spectroscopy and evaluation of parameters related to accuracy of analysis.

PubMed

Lim, Young-Il; Han, Janghee; Woo, Young-Ah; Kim, Jaejin; Kang, Myung Joo

2018-07-05

The purpose of this study was to determine the atorvastatin (ATV) content in process pharmaceutical powder sample using Raman spectroscopy. To establish the analysis method, the influence of the type of Raman measurements (back-scattering or transmission mode), preparation of calibration sample (simple admixing or granulation), sample pre-treatment (pelletization), and spectral pretreatment on the Raman spectra was investigated. The characteristic peak of the active compound was more distinctively detected in transmission Raman mode with a laser spot size of 4mm than in the back-scattering method. Preparation of calibration samples by wet granulation, identical to the actual manufacturing process, provided unchanged spectral patterns for the in process sample, with no changes and/or shifts in the spectrum. Pelletization before Raman analysis remarkably improved spectral reproducibility by decreasing the difference in density between the samples. Probabilistic quotient normalization led to accurate and consistent quantification of the ATV content in the calibration samples (standard error of cross validation: 1.21%). Moreover, the drug content in the granules obtained from five commercial batches were reliably quantified, with no statistical difference (p=0.09) with that obtained by HPLC assay. From these findings, we suggest that transmission Raman analysis may be a fast and non-invasive method for the quantification of ATV in actual manufacturing processes. Copyright © 2018 Elsevier B.V. All rights reserved.

Rapid quantitation of atorvastatin in process pharmaceutical powder sample using Raman spectroscopy and evaluation of parameters related to accuracy of analysis

NASA Astrophysics Data System (ADS)

Lim, Young-Il; Han, Janghee; Woo, Young-Ah; Kim, Jaejin; Kang, Myung Joo

2018-07-01

The purpose of this study was to determine the atorvastatin (ATV) content in process pharmaceutical powder sample using Raman spectroscopy. To establish the analysis method, the influence of the type of Raman measurements (back-scattering or transmission mode), preparation of calibration sample (simple admixing or granulation), sample pre-treatment (pelletization), and spectral pretreatment on the Raman spectra was investigated. The characteristic peak of the active compound was more distinctively detected in transmission Raman mode with a laser spot size of 4 mm than in the back-scattering method. Preparation of calibration samples by wet granulation, identical to the actual manufacturing process, provided unchanged spectral patterns for the in process sample, with no changes and/or shifts in the spectrum. Pelletization before Raman analysis remarkably improved spectral reproducibility by decreasing the difference in density between the samples. Probabilistic quotient normalization led to accurate and consistent quantification of the ATV content in the calibration samples (standard error of cross validation: 1.21%). Moreover, the drug content in the granules obtained from five commercial batches were reliably quantified, with no statistical difference (p = 0.09) with that obtained by HPLC assay. From these findings, we suggest that transmission Raman analysis may be a fast and non-invasive method for the quantification of ATV in actual manufacturing processes.

Experimental study on ignition mechanisms of wet granulation sulfur caused by friction.

PubMed

Dai, Haoyuan; Fan, Jianchun; Wu, Shengnan; Yu, Yanqiu; Liu, Di; Hu, Zhibin

2018-02-15

It is common to see fire accidents caused by friction during the storage and transportation of wet granulation sulfur. To study the sulfur ignition mechanism under friction conditions, a new rotating test apparatus is developed to reproduce friction scenes at lab scale. A series of experiments are performed under different normal loads. The SEM-EDS and the XRD were utilized to examine the morphologies and compositions of the tested specimens and the friction products. Experimental results show that these two methods are mostly in agreement with each other. The iron-sulfide compounds are produced and the proportion of iron-sulfide compounds is reduced with normal loads increasing, compared to the total number of the friction products. The facts implied by the integration analysis of friction products with the temperature changes of the near friction surface unveil an underlying mechanism that may explain sulfur ignition by friction in real scenarios. The sulfur ignition may be mainly caused by the spontaneous combustion of iron sulfide compounds produced by friction under low normal load with 200N. With the increase of normal loads, the resulting iron-sulfide compounds are decreasing and the high temperature from friction heat begins to play a major role in causing fire. Copyright © 2017 Elsevier B.V. All rights reserved.

Relationships of damaged starch granules and particle size distribution with pasting and thermal profiles of milled MR263 rice flour.

PubMed

Asmeda, R; Noorlaila, A; Norziah, M H

2016-01-15

This research was conducted to investigate the effects of different grinding techniques (dry, semi-wet and wet) of milled rice grains on the damaged starch and particle size distribution of flour produced from a new variety, MR263, specifically related to the pasting and thermal profiles. The results indicated that grinding techniques significantly (p<0.05) affected starch damage content and particle size distribution of rice flour. Wet grinding process yields flour with lowest percentage of starch damage (7.37%) and finest average particle size (8.52μm). Pasting and gelatinization temperature was found in the range of 84.45-89.63°C and 59.86-75.31°C, respectively. Dry ground flour attained the lowest pasting and gelatinization temperature as shown by the thermal and pasting profiles. Correlation analysis revealed that percentage of damaged starch granules had a significant, negative relationship with pasting temperature while average particle size distribution had a significant, strong negative relationship with gelatinization temperature. Copyright © 2015 Elsevier Ltd. All rights reserved.

Measuring changes in the mass of single subcellular organelles using x-ray microscopy

NASA Astrophysics Data System (ADS)

Goncz, Kaarin K.; Moronne, Mario M.; Lin, W.; Rothman, Stephen S.

1993-01-01

Using quantitative scanning transmission x-ray microscopy, zymogen granules isolated from pancreatic acinar cells were observed suspended in aqueous medium at 50 nm resolution. From 3.64 nm x-ray absorption data, the protein content and rate of protein efflux from individual granules were determined. This was accomplished with a specially designed silicon nitride based wet-cell that allowed continuous perfusion and monitoring of individual granules in a variety of different aqueous environments. Granules suspended in 300 mM sucrose, 5 mM phosphate buffer (pH 6.0) were observed to continuously decrease in size and protein content over a period of several hours. Sudden lysis of the granules was not observed. From the flux data, the apparent protein permeability coefficients for individual granules were determined to range from 1 - 10 X 10-10 cm/sec with an average of 4.78 +/- 3.0 X 10-10 cm/sec. We believe this is the first quantitative population profile determined for a subcellular organelle developed from measurements of individual members of the population.

Mixing of low-dose cohesive drug and overcoming of pre-blending step using a new gentle-wing high-shear mixer granulator.

PubMed

Alsulays, Bader B; Fayed, Mohamed H; Alalaiwe, Ahmed; Alshahrani, Saad M; Alshetaili, Abdullah S; Alshehri, Sultan M; Alanazi, Fars K

2018-05-16

The objective of this study was to examine the influence of drug amount and mixing time on the homogeneity and content uniformity of a low-dose drug formulation during the dry mixing step using a new gentle-wing high-shear mixer. Moreover, the study investigated the influence of drug incorporation mode on the content uniformity of tablets manufactured by different methods. Albuterol sulfate was selected as a model drug and was blended with the other excipients at two different levels, 1% w/w and 5% w/w at impeller speed of 300 rpm and chopper speed of 3000 rpm for 30 min. Utilizing a 1 ml unit side-sampling thief probe, triplicate samples were taken from nine different positions in the mixer bowl at selected time points. Two methods were used for manufacturing of tablets, direct compression and wet granulation. The produced tablets were sampled at the beginning, middle, and end of the compression cycle. An analysis of variance analysis indicated the significant effect (p < .05) of drug amount on the content uniformity of the powder blend and the corresponding tablets. For 1% w/w and 5% w/w formulations, incorporation of the drug in the granulating fluid provided tablets with excellent content uniformity and very low relative standard deviation (∼0.61%) during the whole tableting cycle compared to direct compression and granulation method with dry incorporation mode of the drug. Overall, gentle-wing mixer is a good candidate for mixing of low-dose cohesive drug and provides tablets with acceptable content uniformity with no need for pre-blending step.

Impact of screw configuration on the particle size distribution of granules produced by twin screw granulation.

PubMed

Vercruysse, J; Burggraeve, A; Fonteyne, M; Cappuyns, P; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

2015-02-01

Twin screw granulation (TSG) has been reported by different research groups as an attractive technology for continuous wet granulation. However, in contrast to fluidized bed granulation, granules produced via this technique typically have a wide and multimodal particle size distribution (PSD), resulting in suboptimal flow properties. The aim of the current study was to evaluate the impact of granulator screw configuration on the PSD of granules produced by TSG. Experiments were performed using a 25 mm co-rotating twin screw granulator, being part of the ConsiGma™-25 system (a fully continuous from-powder-to-tablet manufacturing line from GEA Pharma Systems). Besides the screw elements conventionally used for TSG (conveying and kneading elements), alternative designs of screw elements (tooth-mixing-elements (TME), screw mixing elements (SME) and cutters) were investigated using an α-lactose monohydrate formulation granulated with distilled water. Granulation with only conveying elements resulted in wide and multimodal PSD. Using kneading elements, the width of the PSD could be partially narrowed and the liquid distribution was more homogeneous. However, still a significant fraction of oversized agglomerates was obtained. Implementing additional kneading elements or cutters in the final section of the screw configuration was not beneficial. Furthermore, granulation with only TME or SME had limited impact on the width of the PSD. Promising results were obtained by combining kneading elements with SME, as for these configurations the PSD was narrower and shifted to the size fractions suitable for tableting. Copyright © 2015 Elsevier B.V. All rights reserved.

Enhancing tablet disintegration characteristics of a highly water-soluble high-drug-loading formulation by granulation process.

PubMed

Pandey, Preetanshu; Levins, Christopher; Pafiakis, Steve; Zacour, Brian; Bindra, Dilbir S; Trinh, Jade; Buckley, David; Gour, Shruti; Sharif, Shasad; Stamato, Howard

2018-07-01

The objective of this study was to improve the disintegration and dissolution characteristics of a highly water-soluble tablet matrix by altering the manufacturing process. A high disintegration time along with high dependence of the disintegration time on tablet hardness was observed for a high drug loading (70% w/w) API when formulated using a high-shear wet granulation (HSWG) process. Keeping the formulation composition mostly constant, a fluid-bed granulation (FBG) process was explored as an alternate granulation method using a 2 (4-1) fractional factorial design with two center points. FBG batches (10 batches) were manufactured using varying disingtegrant amount, spray rate, inlet temperature (T) and atomization air pressure. The resultant final blend particle size was affected significantly by spray rate (p = .0009), inlet T (p = .0062), atomization air pressure (p = .0134) and the interaction effect between inlet T*spray rate (p = .0241). The compactibility of the final blend was affected significantly by disintegrant amount (p < .0001), atomization air pressure (p = .0013) and spray rate (p = .05). It was observed that the fluid-bed batches gave significantly lower disintegration times than the HSWG batches, and mercury intrusion porosimetry data revealed that this was caused by the higher internal pore structure of tablets manufactured using the FBG batches.

High performance of treated and washed MSWI bottom ash granulates as natural aggregate replacement within earth-moist concrete.

PubMed

Keulen, A; van Zomeren, A; Harpe, P; Aarnink, W; Simons, H A E; Brouwers, H J H

2016-03-01

Municipal solid waste incineration bottom ash was treated with specially designed dry and wet treatment processes, obtaining high quality bottom ash granulate fractions (BGF) suitable for up to 100% replacement of natural gravel in concrete. The wet treatment (using only water for separating and washing) significantly lowers the leaching of e.g. chloride and sulfate, heavy metals (antimony, molybdenum and copper) and dissolved organic carbon (DOC). Two potential bottom ash granulate fractions, both in compliance with the standard EN 12620 (aggregates for concrete), were added into earth-moist concrete mixtures. The fresh and hardened concrete physical performances (e.g. workability, strength and freeze-thaw) of high strength concrete mixtures were maintained or improved compared with the reference mixtures, even after replacing up to 100% of the initial natural gravel. Final element leaching of monolithic and crushed granular state BGF containing concretes, showed no differences with the gravel references. Leaching of all mixtures did not exceed the limit values set by the Dutch Soil Quality Degree. In addition, multiple-life-phase emission (pH static test) for the critical elements of input bottom ash, bottom ash granulate (BGF) and crushed BGF containing concrete were assessed. Simulation pH lowering or potential carbonation processes indicated that metal (antimony, barium, chrome and copper) and sulfate element leaching behavior are mainly pH dominated and controlled, although differ in mechanism and related mineral abundance. Copyright © 2016 Elsevier Ltd. All rights reserved.

HIGH-SHEAR GRANULATION PROCESS: INFLUENCE OF PROCESSING PARAMETERS ON CRITICAL QUALITY ATTRIBUTES OF ACETAMINOPHEN GRANULES AND TABLETS USING DESIGN OF EXPERIMENT APPROACH.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shedfat, Ramadan I

2017-01-01

Application of quality by design (QbD) in high shear granulation process is critical and need to recognize the correlation between the granulation process parameters and the properties of intermediate (granules) and corresponding final product (tablets). The present work examined the influence of water amount (X,) and wet massing time (X2) as independent process variables on the critical quality attributes of granules and corresponding tablets using design of experiment (DoE) technique. A two factor, three level (32) full factorial design was performed; each of these variables was investigated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their size distribution, density and flow pattern. Additionally, the produced tablets have been investigated for weight uniformity, crushing strength, friability and percent capping, disintegration time and drug dissolution. Statistically significant impact (p < 0.05) of water amount was identified for granule growth, percent fines and distribution width and flow behavior. Granule density and compressibility were found to be significantly influenced (p < 0.05) by the two operating conditions. Also, water amount has significant effect (p < 0.05) on tablet weight unifornity, friability and percent capping. Moreover, tablet disintegration time and drug dissolution appears to be significantly influenced (p < 0.05) by the two process variables. On the other hand, the relationship of process parameters with critical quality attributes of granule and final product tablet was identified and correlated. Ultimately, a judicious selection of process parameters in high shear granulation process will allow providing product of desirable quality.

Eudragit E as excipient for production of granules and tablets from Phyllanthus niruri L spray-dried extract.

PubMed

Pereira de Souza, Tatiane; Martínez-Pacheco, Ramón; Gómez-Amoza, José Luiz; Petrovick, Pedro Ros

2007-04-27

The aim of this study was to investigate the feasibility of using Eudragit E as a granulating agent for a spray-dried extract from Phyllanthus niruri to obtain tablets containing a high dose of this product. The granules were developed by wet granulation and contained 2.5%, 5.0%, and 10.0% Eudragit E in the final product concentration. The tablets were produced on a single-punch tablet press by direct compression of granules using 0.5% magnesium stearate as a lubricant. The tablets were elaborated following a 2 x 3 factorial design, where Eudragit E concentration and compression force were the independent variables, and tensile strength and the extract release of the tablets were the dependent variables. All granules showed better technological properties than the spray-dried extract, including less moisture sorption. The characteristics of the granules were directly dependent on the proportion of Eudragit E in the formulation. In general, all tablets showed high mechanical resistance with less than 1% friability, less moisture sorption, and a slower extract release profile. The Eudragit E concentration and compression force of the tablets significantly influenced both dependent variables studied. In conclusion, Eudragit E was efficient as a granulating agent for the spray-dried extract, but additional studies are needed to further optimize the formulations in order to achieve less water sorption and improve the release of the extract from the tablets.

Evaluation of various processes for simultaneous complexation and granulation to incorporate drug-cyclodextrin complexes into solid dosage forms.

PubMed

Gyanani, Vijay; Siddalingappa, Basavaraj; Betageri, Guru V

2015-01-01

Insoluble drugs often formulated with various excipients to enhance the dissolution. Cyclodextrins (CDs) are widely used excipients to improve dissolution profile of poorly soluble drugs. Drug-CD complexation process is complex and often requires multiple processes to produce solid dosage form. Hence, this study explored commonly used granulation processes for simultaneous complexation and granulation. Poorly soluble drugs ibuprofen and glyburide were selected as experimental drugs. Co-evaporation of drug:CD mixture from a solvent followed by wet granulation with water was considered as standard process for comparison. Spray granulation and fluid bed processing (FBP) using drug:CD solution in ethanol were evaluated as an alternative processes. The dissolution data of glyburide tablets indicated that tablets produced by spray granulation, FBP and co-evaporation-granulation have almost identical dissolution profile in water and 0.1% SLS (>70% in water and >60% in SLS versus 30 and 34%, respectively for plain tablet, in 120 min). Similarly, ibuprofen:CD tablets produced by co-evaporation-granulation and FBP displayed similar dissolution profile in 0.01 M HCl (pH 2.0) and buffer pH 5.5 (>90 and 100% versus 44 and 80% respectively for plain tablets, 120 min). Results of this study demonstrated that spray granulation is simple and cost effective process for low dose poorly soluble drugs to incorporate drug:CD complex into solid dosage form, whereas FBP is suitable for poorly soluble drugs with moderate dose.

Investigation of Oral Preparation That Is Expected to Improve Medication Administration: Preparation and Evaluation of Oral Gelling Tablet Using Sodium Alginate.

PubMed

Ito, Ikumi; Ito, Akihiko; Unezaki, Sakae

2017-01-01

We investigated the preparation of a gelling tablet that swells and forms a gel upon absorbing water, and hence would be easy for patients to swallow. We prepared naked tablets and compressed coated tablets by the direct tableting or wet granule-compression methods, using the commonly prescribed drug acetaminophen (AA) and sodium alginate (AG) as a thickening agent. The tablets quickly absorbed water, had favorable gelling properties, low adhesiveness, appropriate drug dissolution profile, and at the same time, were easy to swallow. In the case of naked tablets, water absorption increased upon granulation, but gelling of AG interfere when AA and AG were present together. There was no change in the adhesiveness, and more than 30 min were required to achieve a 25% dissolution ratio. Compressed coated tablets that were made with AA in the inner layer and granulated AG in the outer layer showed improved dissolution behavior, it was about 90% dissolution ratio in 30 min, owing to the water absorption property of AG, and decreased adhesiveness. In this case, there was a difference in the outer layer thickness. As the outer layer amount increased, dissolution slowed, but it did not depend on the compression pressure. Our gelling tablet can be prepared by using AA (main drug) in the inner layer and an appropriate thickness of granulated AG in the outer layer of compressed coated tablets.

A study on maize proteins as a potential new tablet excipient.

PubMed

Georget, Dominique M R; Barker, Susan A; Belton, Peter S

2008-06-01

This investigation has examined the use of zein proteins from maize as the major component in oral controlled-release tablets, such formulations often being required to improve patient compliance. Tablets containing ground zein proteins, calcium hydrogen orthophosphate, polyvinyl pyrrolidone, theophylline and magnesium stearate were produced by wet granulation and compression on a single station tablet press and were compared to directly compressed tablets based on zein proteins, calcium hydrogen orthophosphate and theophylline. Non invasive techniques such as Fourier Transform infrared spectroscopy and Fourier Transform Raman spectroscopy were employed to investigate any changes in the secondary structure of zein proteins during tablet production. Random coils, alpha helices and beta sheets predominated and their relative content remained unaffected during grinding, wet granulation and compression, indicating that formulations based on zeins will be robust, i.e. insensitive to minor changes in the production conditions. Drug release from the tablets was studied using a standard pharmacopoeial dissolution test. Dissolution profiles in water, 0.1M HCl (pH=1) and phosphate buffer (pH=6.8) show that only a limited amount of theophylline was released after 4.5h, suggesting that zein proteins could act as a potential vehicle for oral controlled drug release. Analysis of the theophylline release profiles using the Peppas and Sahlin model reveals that diffusion and polymer relaxation occurred in acidic (pH=1) and buffered (pH=6.8) conditions for wet granulated tablets, whereas diffusion was predominant in directly compressed tablets. In conclusion, the present study has shown that zeins can be successfully used as a pharmaceutical excipient, and in particular as a matrix in monolithic controlled release tablets.

HIGH SHEAR GRANULATION PROCESS: ASSESSING IMPACT OF FORMULATION VARIABLES ON GRANULES AND TABLETS CHARACTERISTICS OF HIGH DRUG LOADING FORMULATION USING DESIGN OF EXPERIMENT METHODOLOGY.

PubMed

Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Ali, Bahaa E

2017-03-01

High shear wet granulation is a significant component procedure in the pharmaceutical industry. The objective of the study was to investigate the influence of two independent formulation variables; polyvinypyrrolidone (PVP) as a binder (X,) and croscarmellose sodium (CCS) as a disintegrant (X2) on the crit- ical quality attributes of acetaminophen granules and their corresponding tablets using design of experiment (DoE) approach. A two factor, three level (32) full factorial design has been applied; each variable was investi- gated at three levels to characterize their strength and interaction. The dried granules have been analyzed for their density, granule size and flowability. Additionally, the produced tablets have been investigated for: break- ing force, friability, disintegration time and t. of drug dissolution. The analysis of variance (ANOVA) showed that the two variables had a significant impact (p < 0.05) on granules and tablets characteristics, while only the binder concentration influenced the tablets friability. Furthermore, significant interactions (p < 0.05) between the two variables, for granules and tablets attributes, were also found. However, variables interaction showed minimal effect for granules flowability as well as tablets friability. Desirability function was carried out to opti- mize the variables under study to obtain product within the USP limit. It was found that the higher desirability (0.985) could be obtained at the medium level of PVP and low level of CCS. Ultimately, this study supplies the formulator with beneficial tools in selecting the proper level of binder and disintegrant to attain product with desired characteristics.

Acoustic emission monitoring from a lab scale high shear granulator--a novel approach.

PubMed

Watson, N J; Povey, M J W; Reynolds, G K; Xu, B H; Ding, Y

2014-04-25

A new approach to the monitoring of granulation processes using passive acoustics together with precise control over the granulation process has highlighted the importance of particle-particle and particle-bowl collisions in acoustic emission. The results have shown that repeatable acoustic results could be obtained but only when a spray nozzle water addition system was used. Acoustic emissions were recorded from a transducer attached to the bowl and an airborne transducer. It was found that the airborne transducer detected very little from the granulation and only experienced small changes throughout the process. The results from the bowl transducer showed that during granulation the frequency content of the acoustic emission shifted towards the lower frequencies. Results from the discrete element model indicate that when larger particles are used the number of collisions the particles experience reduces. This is a result of the volume conservation methodology used in this study, therefore larger particles results in less particles. These simulation results coupled with previous theoretical work on the frequency content of an impacting sphere explain why the frequency content of the acoustic emissions reduces during granule growth. The acoustic system used was also clearly able to identify when large over-wetted granules were present in the system, highlighting its benefit for detecting undesirable operational conditions. High-speed photography was used to study if visual changes in the granule properties could be linked with the changing acoustic emissions. The high speed photography was only possible towards the latter stages of the granulation process and it was found that larger granules produced a higher magnitude of acoustic emission across a broader frequency range. Copyright © 2014 Elsevier B.V. All rights reserved.

Design, development and method validation of a novel multi-resonance microwave sensor for moisture measurement.

PubMed

Peters, Johanna; Taute, Wolfgang; Bartscher, Kathrin; Döscher, Claas; Höft, Michael; Knöchel, Reinhard; Breitkreutz, Jörg

2017-04-08

Microwave sensor systems using resonance technology at a single resonance in the range of 2-3 GHz have been shown to be a rapid and reliable tool for moisture determination in solid materials including pharmaceutical granules. So far, their application is limited to lower moisture ranges or limitations above certain moisture contents had to be accepted. Aim of the present study was to develop a novel multi-resonance sensor system in order to expand the measurement range. Therefore, a novel sensor using additional resonances over a wide frequency band was designed and used to investigate inherent limitations of first generation sensor systems and material-related limits. Using granule samples with different moisture contents, an experimental protocol for calibration and validation of the method was established. Pursuant to this protocol, a multiple linear regression (MLR) prediction model built by correlating microwave moisture values to the moisture determined by Karl Fischer titration was chosen and rated using conventional criteria such as coefficient of determination (R 2 ) and root mean square error of calibration (RMSEC). Using different operators, different analysis dates and different ambient conditions the method was fully validated following the guidance of ICH Q2(R1). The study clearly showed explanations for measurement uncertainties of first generation sensor systems which confirmed the approach to overcome these by using additional resonances. The established prediction model could be validated in the range of 7.6-19.6%, demonstrating its fit for its future purpose, the moisture content determination during wet granulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Enhanced dissolution of sildenafil citrate as dry foam tablets.

PubMed

Sawatdee, Somchai; Atipairin, Apichart; Sae Yoon, Attawadee; Srichana, Teerapol; Changsan, Narumon

2017-01-30

Dry foam formulation technology is alternative approach to enhance dissolution of the drug. Sildenafil citrate was suspended in sodium dodecyl sulfate solution and adding a mixture of maltodextrin and mannitol as diluent to form a paste. Sildenafil citrate paste was passed through a nozzle spray bottle to obtain smooth foam. The homogeneous foam was dried in a vacuum oven and sieved to obtain dry foam granules. The granules were mixed with croscarmellose sodium, magnesium stearate and compressed into tablet. All formulations were evaluated for their physicochemical properties and dissolution profiles. All the tested excipients were compatible with sildenafil citrate by both differential scanning calorimetry (DSC) and infrared (IR) analysis. There are no X-ray diffraction (XRD) peaks representing crystals of sildenafil citrate observed form dry foam formulations. The hardness of tablets was about 5 kg, friability test <1% with a disintegration time <5 min. The sildenafil citrate dry foam tablet had higher dissolution rate in 0.1 N HCl in comparison with commercial sildenafil citrate tablet, sildenafil citrate prepared by direct compression and wet granulation method. Sildenafil citrate dry foam tablet with the high-level composition of surfactant, water and diluent showed enhanced dissolution rate than that of the lower-level composition of these excipients. This formulation was stable under accelerated conditions for at least 6 months.

Influence of granulating method on physical and mechanical properties, compression behavior, and compactibility of lactose and microcrystalline cellulose granules.

PubMed

Horisawa, E; Danjo, K; Sunada, H

2000-06-01

The physical and mechanical properties of lactose (LC) and microcrystalline cellulose (MCC) granules prepared by various granulating methods were determined, and their effects on the compression and strength of the tablets were examined. From the force-displacement curve obtained in a crushing test on a single granule, all LC granules appeared brittle, and MCC granules were somewhat plastically deformable. Inter-granular porosity epsilon inter clearly decreased with greater spherical granule shape for both materials. Decrease in intragranular porosity epsilon intra enhanced the crushing force of a single granule Fg. Agitating granulation brought about the most compactness and hardness of granules. In granule compression tests, the initial slope of Heckel plots K1 appeared closely related to ease of filling voids in a granule bed by the slippage or rolling of granules. The reciprocal of the slope in the succeeding step 1/K2 in compression of MCC granules indicated positive correlation to Fg, while in LC granules, no such obvious relation was evident. 1/K2 differed only slightly among granulating methods. Tensile strength of tablets Tt obtained by compression of various LC granules was low as a whole and was little influenced by granulating method. For MCC granules, which are plastically deformable, tablet strength greatly depended on granulation. Granules prepared by extruding or dry granulation gave strong tablets. Tablets prepared from granules made by the agitating method showed particularly low Tt. From stereomicroscopic observation, the contact area between granule particles in a tablet appeared smaller; this would explain the decrease in inter-granular bond formation.

Phase transformation in thiamine hydrochloride tablets: Influence on tablet microstructure, physical properties, and performance.

PubMed

Chakravarty, Paroma; Suryanarayanan, Raj; Govindarajan, Ramprakash

2012-04-01

The objective of this article was to monitor phase transformation in thiamine hydrochloride, from a nonstoichiometric hydrate (NSH) to a hemihydrate (HH), in stored tablets, prepared both by direct compression and wet granulation, and to relate the storage-induced phase transformation with changes in tablet microstructure, physical properties, and performance. Raman spectroscopy revealed complete NSH → HH transformation in tablets, within 30 h of storage at 40°C/75% relative humidity. When the tablets were prepared by wet granulation of NSH alone, there was a marked increase in both tablet volume and hardness on storage. However, when microcrystalline cellulose (MCC) was included in granulation, the resulting stored tablets also exhibited a pronounced increase in disintegration time. In contrast, tablets prepared by dry processing via compression of a NSH-MCC physical mixture did not exhibit any changes in properties, despite the in situ solid form conversion. Scanning electron microscopy revealed growth of needle-like HH crystals in all stored tablets and mercury porosimetry revealed considerable changes in the pore size distribution during storage. Longer storage led to crystal growth (Ostwald ripening), causing further gradual but less dramatic changes in properties. The phase transformation and the complex interparticulate associations in the tablet influenced the changes in tablet microstructure, compact physical properties, and product behavior. Copyright © 2011 Wiley Periodicals, Inc.

Evaluation of the wound-healing activity of Hibiscus rosa sinensis L (Malvaceae) in Wistar albino rats.

PubMed

Bhaskar, Anusha; Nithya, V

2012-01-01

To investigate the wound-healing potency of the ethanolic extract of the flowers of Hibiscus rosa sinensis. The wound-healing activity of H. rosa sinensis (5 and 10% w/w) on Wistar albino rats was studied using three different models viz., excision, incision and dead space wound. The parameters studied were breaking strength in incision model, granulation tissue dry weight, breaking strength and collagen content in dead space wound model, percentage of wound contraction and period of epithelization in excision wound model. The granulation tissue formed on days 4, 8, 12, and 16 (post-wound) was used to estimate total collagen, hexosamine, protein, DNA and uronic acid. Data were analyzed by Analysis of Variance (ANOVA) test. P<0.05 was considered statistically significant. The extract increased cellular proliferation and collagen synthesis at the wound site, as evidenced by increase in DNA, total protein and total collagen content of granulation tissues. The extract-treated wounds were found to heal much faster as indicated by improved rates of epithelialization and wound contraction. The extract of H. rosa sinensis significantly (P<0.001) increased the wound-breaking strength in the incision wound model compared to controls. The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly (P<0.001) increased as compared to control wounds. Wet and dry granulation tissue weights in a dead space wound model increased significantly (P<0.001). There was a significant increase in wound closure rate, tensile strength, dry granuloma weight, wet granuloma weight and decrease in epithelization period in H. rosa sinensis-treated group as compared to control and standard drug-treated groups. The ethanolic extract of H. rosa sinensis had greater wound-healing activity than the nitrofurazone ointment.

Improving in vivo conversion of oleuropein into hydroxytyrosol by oral granules containing probiotic Lactobacillus plantarum 299v and an Olea europaea standardized extract.

PubMed

Aponte, Maria; Ungaro, Francesca; d'Angelo, Ivana; De Caro, Carmen; Russo, Roberto; Blaiotta, Giuseppe; Dal Piaz, Fabrizio; Calignano, Antonio; Miro, Agnese

2018-05-30

This study reports novel food-grade granules for co-delivery of L. plantarum 299v and a standardized extract of Olea europaea leaves (Phenolea®) as oral carrier of probiotics and hydroxytyrosol. Different granule formulations containing either L. plantarum 299v (Lac), or the olive leave extract (Phe) or their combination (Lac-Phe) have been successfully produced through wet granulation employing excipients generally regarded as safe as granulating/binding agents. L. plantarum cells withstood the manufacturing process and were stable upon storage at 4 °C for more than 6 months. In vitro dissolution studies in simulated gastro-intestinal fluids showed the capability of the granules to rapidly dissolve and deliver both olive leave phenols and living L. plantarum cells. In simulated digestion conditions, Lac and Lac-Phe granules protected L. plantarum against the harsh environment of the gastro-intestinal tract. Co-administration of Lac and Phe oral granules to healthy mice provided for higher amounts of hydroxytyrosol in urines as compared to Phe granules alone, suggesting that L. plantarum 299v boosted in vivo conversion of oleuropein to hydroxytyrosol. On the other hand, PCR-assisted profiling of the Lactobacillus population in faeces obtained from mice treated with Lac or Lac plus Phe confirmed that the probiotic arrived alive to colon and was there able to exert a sort of perturbing effect on the climax colonic microflora. Overall, these results pave the way towards the development of a nutraceutical useful for combined delivery of bioactive hydroxytyrosol and probiotics to colon site. Copyright © 2018 Elsevier B.V. All rights reserved.

Simplified formulations with high drug loads for continuous twin-screw granulation.

PubMed

Meier, R; Thommes, M; Rasenack, N; Krumme, M; Moll, K-P; Kleinebudde, P

2015-12-30

As different batches of the same excipients will be intermixed during continuous processes, the traceability of batches is complicated. Simplified formulations may help to reduce problems related to batch intermixing and traceability. Twin-screw granulation with subsequent tableting was used to produce granules and tablets, containing drug, disintegrant and binder (binary and ternary mixtures), only. Drug loads up to 90% were achieved and five different disintegrants were screened for keeping their disintegration suitability after wetting. Granule size distributions were consistently mono-modal and narrow. Granule strength reached higher values, using ternary mixtures. Tablets containing croscarmellose-Na as disintegrant displayed tensile strengths up to 3.1MPa and disintegration times from 400 to 466s, resulting in the most robust disintegrant. Dissolution was overall complete and above 96% within 30 min. Na-starch glycolate offers tensile strengths up to 2.8MPa at disintegration times from 25s to 1031s, providing the broadest application window, as it corresponds in some parts to different definitions of orodispersible tablets. Tablets containing micronized crospovidone are not suitable for immediate release, but showed possibilities to produce highly drug loaded, prolonged release tablets. Tablets and granules from simplified formulations offer great opportunities to improve continuous processes, present performances comparable to more complicated formulations and are able to correspond to requirements of the authorities. Copyright © 2015 Elsevier B.V. All rights reserved.

Zinc-Nucleated D 2 and H 2 Crystal Formation from Their Liquids

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bernat, T. P.; Petta, N.; Kozioziemski, B.

Calorimetric measurements at University of Rochester Laboratory for Laser Energetics of D 2 crystallization from the melt indicate that zinc can act as a heterogeneous nucleation seed with suppressed supercooling. We further studied in this paper this effect for a variety of zinc substrates using the optical-access cryogenic sample cell at Lawrence Livermore National Laboratory. Small supercoolings are observed, some as low as 5 mK, but results depend on the zinc history and sample preparation. In general, thin samples prepared by physical vapor deposition were not effective in nucleating crystal formation. Larger (several-millimeter) granules showed greater supercooling suppression, depending onmore » surface modification and granule size. Surfaces of these granules are morphologically varied and not uniform. Scanning electron microscope images were not able to correlate any particular surface feature with enhanced nucleation. Finally, application of classical nucleation theory to the observed variation of supercooling level with granule size is consistent with nucleation features with sizes <100 nm and with wetting angles of a few degrees.« less

Imaging wet granules with different flow patterns by electrical capacitance tomography and microwave tomography

NASA Astrophysics Data System (ADS)

Wang, H. G.; Zhang, J. L.; Ramli, M. F.; Mao, M. X.; Ye, J. M.; Yang, W. Q.; Wu, Z. P.

2016-11-01

The moisture content of granules in fluidised bed drying, granulation and coating processes can typically be between 1%~25%, resulting in the change of permittivity and conductivity during the processes. Electrical capacitance tomography (ECT) has been used for this purpose, but has a limit because too much water can cause a problem in capacitance measurement. Considering that microwave tomography (MWT) has a wide range of frequency (1~2.5 GHz) and can be used to measure materials with high permittivity and conductivity, the objective of this research is to combine ECT and MWT together to investigate the solids concentration with different moisture content and different flow patterns. The measurement results show that both ECT and MWT are functions of moisture content as well as flow patterns, and their measurements are complementary to each other. This is the first time that these two tomography modalities have been combined together and applied to image the complex solids distribution. The obtained information may be used for the process control of fluidised bed drying, granulation and coating to improve operation efficiency.

Zinc-Nucleated D 2 and H 2 Crystal Formation from Their Liquids

DOE PAGES

Bernat, T. P.; Petta, N.; Kozioziemski, B.; ...

2016-09-01

Calorimetric measurements at University of Rochester Laboratory for Laser Energetics of D 2 crystallization from the melt indicate that zinc can act as a heterogeneous nucleation seed with suppressed supercooling. We further studied in this paper this effect for a variety of zinc substrates using the optical-access cryogenic sample cell at Lawrence Livermore National Laboratory. Small supercoolings are observed, some as low as 5 mK, but results depend on the zinc history and sample preparation. In general, thin samples prepared by physical vapor deposition were not effective in nucleating crystal formation. Larger (several-millimeter) granules showed greater supercooling suppression, depending onmore » surface modification and granule size. Surfaces of these granules are morphologically varied and not uniform. Scanning electron microscope images were not able to correlate any particular surface feature with enhanced nucleation. Finally, application of classical nucleation theory to the observed variation of supercooling level with granule size is consistent with nucleation features with sizes <100 nm and with wetting angles of a few degrees.« less

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules V. Release properties of ethylcellulose layered matrix granules.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2008-04-01

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. In previous papers, a combination of the square-root time law and cube-root law equations was confirmed to be a useful equation for qualitative treatment. It was also confirmed that the combination equation could analyze the release properties of layered granules as well as matrix granules. The drug release property from layered granules is different from that of matrix granules. A time lag occurs before release, and the entire release property of layered granules was analyzed using the combination of the square-root time law and cube-root law equations. It is considered that the analysis method is very useful and efficient for both matrix and layered granules. Comparing the granulation methods, it is easier to control the manufacturing process by tumbling granulation (method B) than by tumbling-fluidized bed granulation (method C). Ethylcellulose (EC) layered granulation by a fluidized bed granulator might be convenient for the preparation of controlled release dosage forms as compared with a tumbling granulator, because the layered granules prepared by the fluidized bed granulator can granulate and dry at the same time. The time required for drying by the fluidized bed granulator is shorter than that by the tumbling granulator, so the fluidized bed granulator is convenient for preparation of granules in handling and shorter processing time than the tumbling granulator. It was also suggested that the EC layered granules prepared by the fluidized bed granulator were suitable for a controlled release system as well as the EC matrix granules.

Granular flow: Dry and wet

NASA Astrophysics Data System (ADS)

Mitarai, N.; Nakanishi, H.

2012-04-01

Granular material is a collection of macroscopic particles that are visible with naked eyes. The non-equilibrium nature of the granular materials makes their rheology quite different from that of molecular systems. In this minireview, we present the unique features of granular materials focusing on the shear flow of dry granular materials and granule-liquid mixture.

40 CFR 421.76 - Pretreatment standards for new sources.

Code of Federal Regulations, 2013 CFR

2013-07-01

... produced Lead .000 .000 Zinc .000 .000 (g) Subpart G—Hard Lead Refining Slag Granulation. PSNS Pollutant or... hard lead produced Lead .000 .000 Zinc .000 .000 (h) Subpart G—Hard Lead Refining Wet Air Pollution... (pounds per billion pounds) of hard lead produced Lead .000 .000 Zinc .000 .000 (i) Subpart G—Facility...

40 CFR 421.75 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2012 CFR

2012-07-01

... (g) Subpart G—Hard Lead Refining Slag Granulation. PSES Pollutant or pollutant property Maximum for any 1 day Maximum for monthly average mg/kkg (pounds per billion pounds) of hard lead produced Lead .000 .000 Zinc .000 .000 (h) Subpart G—Hard Lead Refining Wet Air Pollution Control. PSES Pollutant or...

40 CFR 421.75 - Pretreatment standards for existing sources.

Code of Federal Regulations, 2013 CFR

2013-07-01

... (g) Subpart G—Hard Lead Refining Slag Granulation. PSES Pollutant or pollutant property Maximum for any 1 day Maximum for monthly average mg/kkg (pounds per billion pounds) of hard lead produced Lead .000 .000 Zinc .000 .000 (h) Subpart G—Hard Lead Refining Wet Air Pollution Control. PSES Pollutant or...

40 CFR 421.76 - Pretreatment standards for new sources.

Code of Federal Regulations, 2012 CFR

2012-07-01

... produced Lead .000 .000 Zinc .000 .000 (g) Subpart G—Hard Lead Refining Slag Granulation. PSNS Pollutant or... hard lead produced Lead .000 .000 Zinc .000 .000 (h) Subpart G—Hard Lead Refining Wet Air Pollution... (pounds per billion pounds) of hard lead produced Lead .000 .000 Zinc .000 .000 (i) Subpart G—Facility...

40 CFR 421.76 - Pretreatment standards for new sources.

Code of Federal Regulations, 2010 CFR

2010-07-01

... produced Lead .000 .000 Zinc .000 .000 (g) Subpart G—Hard Lead Refining Slag Granulation. PSNS Pollutant or... production Lead .000 .000 Zinc .000 .000 (b) Subpart G—Blast Furnace Wet Air Pollution Control. PSNS... pounds) of blast furnace lead bullion produced Lead .000 .000 Zinc .000 .000 (c) Subpart G—Blast Furnace...

40 CFR 421.76 - Pretreatment standards for new sources.

Code of Federal Regulations, 2011 CFR

2011-07-01

... produced Lead .000 .000 Zinc .000 .000 (g) Subpart G—Hard Lead Refining Slag Granulation. PSNS Pollutant or... production Lead .000 .000 Zinc .000 .000 (b) Subpart G—Blast Furnace Wet Air Pollution Control. PSNS... pounds) of blast furnace lead bullion produced Lead .000 .000 Zinc .000 .000 (c) Subpart G—Blast Furnace...

Identifying overarching excipient properties towards an in-depth understanding of process and product performance for continuous twin-screw wet granulation.

PubMed

Willecke, N; Szepes, A; Wunderlich, M; Remon, J P; Vervaet, C; De Beer, T

2017-04-30

The overall objective of this work is to understand how excipient characteristics influence the process and product performance for a continuous twin-screw wet granulation process. The knowledge gained through this study is intended to be used for a Quality by Design (QbD)-based formulation design approach and formulation optimization. A total of 9 preferred fillers and 9 preferred binders were selected for this study. The selected fillers and binders were extensively characterized regarding their physico-chemical and solid state properties using 21 material characterization techniques. Subsequently, principal component analysis (PCA) was performed on the data sets of filler and binder characteristics in order to reduce the variety of single characteristics to a limited number of overarching properties. Four principal components (PC) explained 98.4% of the overall variability in the fillers data set, while three principal components explained 93.4% of the overall variability in the data set of binders. Both PCA models allowed in-depth evaluation of similarities and differences in the excipient properties. Copyright © 2017. Published by Elsevier B.V.

Understanding effect of formulation and manufacturing variables on the critical quality attributes of warfarin sodium product.

PubMed

Rahman, Ziyaur; Korang-Yeboah, Maxwell; Siddiqui, Akhtar; Mohammad, Adil; Khan, Mansoor A

2015-11-10

Warfarin sodium (WS) is a narrow therapeutic index drug and its product quality should be thoroughly understood and monitored in order to avoid clinical performance issues. This study was focused on understanding the effect of manufacturing and formulation variables on WS product critical quality attributes (CQAs). Eight formulations were developed with lactose monohydrate (LM) or lactose anhydrous (LA), and were either wet granulated or directly compressed. Formulations were granulated either with ethanol, isopropyl alcohol (IPA) and IPA-water mixture (50:50). Formulations were characterized for IPA, water content, hardness, disintegration time (DT), assay, dissolution and drug physical forms (scanning electron microscopy (SEM), near infrared chemical imaging (NIR-CI), X-ray powder diffraction (XRPD) and solid state nuclear magnetic resonance (ssNMR)), and performed accelerated stability studies at 40°C/75% RH for three days. The DT and dissolution of directly compressed formulations were faster than wet granulated formulations. This was due to phase transformation of crystalline drug into its amorphous form as indicated by SEM, NIR-CI, XRPD and ssNMR data which itself act as a binder. Similarly, LM showed faster disintegration and dissolution than LA containing formulations. Stability results indicated an increase in hardness and DT, and a decrease in dissolution rate and extent. This was due to phase transformation of the drug and consolidation with particles' bonding. In conclusion, the CQAs of WS product were significantly affected by manufacturing and formulation variables. Published by Elsevier B.V.

[Application of quality by design in granulation process for ginkgo leaf tablet (Ⅱ)： identification of critical quality attributes].

PubMed

Xu, Bing; Cui, Xiang-Long; Yang, Chan; Wang, Xin; Shi, Xin-Yuan; Qiao, Yan-Jiang

2017-03-01

Quality by design (QbD) highlights the concept of "begin with the end", which means to thoroughly understand the target product quality first, and then guide pharmaceutical process development and quality control throughout the whole manufacturing process. In this paper, the Ginkgo biloba granules intermediates were taken as the research object, and the requirements of the tensile strength of tablets were treated as the goals to establish the methods for identification of granules' critical quality attributes (CQAs) and establishment of CQAs' limits. Firstly, the orthogonal partial least square (OPLS) model was adopted to build the relationship between the micromeritic properties of 29 batches of granules and the tensile strength of ginkgo leaf tablets, and thereby the potential critical quality attributes (pCQAs) were screened by variable importance in the projection (VIP) indexes. Then, a series of OPLS models were rebuilt by reducing pCQAs variables one by one in view of the rule of VIP values from low to high in sequence. The model performance results demonstrated that calibration and predictive performance of the model had no decreasing trend after variables reduction. In consideration of the results from variables selection as well as the collinearity test and testability of the pCQAs, the median particle size (D₅₀) and the bulk density (Da) were identified as critical quality attributes (CQAs). The design space of CQAs was developed based on a multiple linear regression model established between the CQAs (D₅₀ and Da) and the tensile strength. The control constraints of the CQAs were determined as 170 μm< D₅₀<500 μm and 0.30 g•cm⁻³

Development and evaluation of 6-mercaptopurine and metoclopramide polypill formulation for oral administration: In-vitro and ex vivo studies

PubMed Central

Chowdhary, Rajani; Pai, Roopa S; Singh, Gurinder

2013-01-01

Introduction: The present investigation was to develop a polypill of 6-mercaptopurine and metoclopramide. A polypill with delayed release granules of an anticancer and immediate release mucoadhesive tablet of antiemetic may result in the reduction of emesis caused by oral chemotherapy. Materials and Methods: 6-Mercaptopurine granules were prepared by wet granulation process. Chitosan, hydroxypropyl methylcellulose, and ethylcellulose were used as individually as delayed release polymers. Seven granule formulations (F1-F7) were prepared and evaluated for flow properties and drug content. Immediate release mucoadhesive tablets of metoclopramide were prepared by direct compression technique using pectin and PVPK-40 as mucoadhesive polymers. Three formulations of pectin (L1-L3) and three formulations of PVPK40 (M1-M3) were prepared using lactose, magnesium stearate, and mannitol and talc as diluent and glidant, respectively. Tablets were evaluated for weight variation, hardness, friability, drug content, ex vivo mucoadhesion time, and in vitro dissolution studies. Results: Formulation F2, F4, F5, and F7 showed maximum drug content. Formulation F7 exhibited the drug release up to 2 h and was selected as the best delayed release formulation. All formulations of metoclopramide showed good drug content ranging from 97.6 % to 100.6%. Formulation M2 among tablets prepared with PVP exhibited desired mucoadhesion time of 15.33 min which prolongs the duration of drug release in gastric pouch of the male Wistar rats. Both the selected formulations F7 and M2 were filled into body of capsule size 0 and capsule was evaluated for technological properties. Conclusion: It may be concluded that polypill released the metoclopramide immediately prior to 6-mercaptopurine. PMID:24350042

Pharmaceutical production of tableting granules in an ultra-small-scale high-shear granulator as a pre-formulation study.

PubMed

Ogawa, Tatsuya; Uchino, Tomohiro; Takahashi, Daisuke; Izumi, Tsuyoshi; Otsuka, Makoto

2012-11-01

In some of drug developments, the amount of bulk drug powder to use in early stages is limited and it is not easy to supply a sufficient drug amount for conventional preparation methods. Therefore, an ultra-small-scale high-shear granulator (less than 5 g) (USG) was developed and applied to small-scale granulation as a pre-formulation. The sample powder consisted of 66.5% lactose, 28.5% microcrystalline cellulose and 5.0% hydroxypropylcellulose. The granules were obtained to agitate 5 g of the sample powder with 1.0 mL of water at 300 rpm for 5 min after pre-powder mixing for 3 min by the USG and the manual hand (HM) methods. The granules were evaluated by the 10% and 90% accumulated particle size and the recoveries of the granules and the powder solid. Median particle size for the USG and the HM methods was 159.2 ± 2.3 and 270.9 ± 14.9 µm, respectively. The USG method had a narrower particle size distribution than those by the HM method. The recovery of the granules by USG was significantly larger than that by the HM method. Characteristics of all of the granules indicated that the USG method could produce higher quality granules within a shorter time than the HM methods.

Using Residence Time Distributions (RTDs) to Address the Traceability of Raw Materials in Continuous Pharmaceutical Manufacturing.

PubMed

Engisch, William; Muzzio, Fernando

Continuous processing in pharmaceutical manufacturing is a relatively new approach that has generated significant attention. While it has been used for decades in other industries, showing significant advantages, the pharmaceutical industry has been slow in its adoption of continuous processing, primarily due to regulatory uncertainty. This paper aims to help address these concerns by introducing methods for batch definition, raw material traceability, and sensor frequency determination. All of the methods are based on established engineering and mathematical principles, especially the residence time distribution (RTD). This paper introduces a risk-based approach to address content uniformity challenges of continuous manufacturing. All of the detailed methods are discussed using a direct compaction manufacturing line as the main example, but the techniques can easily be applied to other continuous manufacturing methods such as wet and dry granulation, hot melt extrusion, capsule filling, etc.

Elaboration of Alumina-Zirconia Composites: Role of the Zirconia Content on the Microstructure and Mechanical Properties

PubMed Central

Naglieri, Valentina; Palmero, Paola; Montanaro, Laura; Chevalier, Jérôme

2013-01-01

Alumina-zirconia (AZ) composites are attractive structural materials, which combine the high hardness and Young’s modulus of the alumina matrix with additional toughening effects, due to the zirconia dispersion. In this study, AZ composites containing different amounts of zirconia (in the range 5–20 vol %) were prepared by a wet chemical method, consisting on the surface coating of alumina powders by mixing them with zirconium salt aqueous solutions. After spray-drying, powders were calcined at 600 °C for 1 h. Green bodies were then prepared by two methods: uniaxial pressing of spray-dried granules and slip casting of slurries, obtained by re-dispersing the spray dried granulates. After pressureless sintering at 1500 °C for 1 h, the slip cast samples gave rise to fully dense materials, characterized by a quite homogeneous distribution of ZrO2 grains in the alumina matrix. The microstructure, phase composition, tetragonal to monoclinic transformation behavior and mechanical properties were investigated and are here discussed as a function of the ZrO2 content. The material containing 10 vol % ZrO2 presented a relevant hardness and exhibited the maximum value of KI0, mainly imputable to the t → m transformation at the crack tip. PMID:28809262

Evaluation of the composition of the binder bridges in matrix granules prepared with a small-scale high-shear granulator.

PubMed

Bajdik, János; Baki, Gabriella; Szent-Királlyi, Zsuzsanna; Knop, Klaus; Kleinebudde, Peter; Pintye-Hódi, Klára

2008-11-04

The aim of this work was to evaluate the binder bridges which can form in hydrophilic matrix granules prepared with a small-scale high-shear granulator. Matrices contained hydroxypropyl methylcellulose (HPMC) as a matrix-forming agent, together with lactose monohydrate and microcrystalline cellulose as filler. Water was used as granulating liquid. A 2(4) full factorial design was used to evaluate the effects of the operational parameters (impeller speed, chopper speed, dosing speed and wet massing time) on the granulation process. The temperature of the sample increased relevantly during the preparation in the small-scale apparatus. The same setup induced different temperature increases for different amounts of powder. This alteration enhances the solubility of lactose and decreases that of HPMC, and thus the quantities of the dissolved components can vary. Accordingly, changes in composition of the binder bridge can occur. Since exact determination of the dissolution of these materials during granulation is difficult, the consequences of the changes in solubility were examined. Differential scanning calorimetry (DSC), thermomechanical analysis (TMA) and X-ray diffraction (XRD) measurements were made to evaluate the films prepared from liquids with different ratios of soluble materials. The DSC and XRD measurements confirmed that the lactose lost its crystalline state in the film. The TMA tests revealed that increase of the quantity of lactose in the film decreased the glass transition temperature of the film; this may be attributed to the interaction of the additives. At a lactose content of 37.5%, a second glass transition appeared. This phenomenon may be indicative of a separate amorphous lactose phase.

Preparation and in vitro evaluation of guar gum based triple-layer matrix tablet of diclofenac sodium

PubMed Central

Chavda, H.V.; Patel, M.S.; Patel, C.N.

2012-01-01

The objective of the present study was to design an oral controlled drug delivery system for sparingly soluble diclofenac sodium (DCL) using guar gum as triple-layer matrix tablets. Matrix tablet granules containing 30% (D1), 40% (D2) or 50% (D3) of guar gum were prepared by the conventional wet granulation technique. Matrix tablets of diclofenac sodium were prepared by compressing three layers one by one. Centre layer of sandwich like structure was incorporated with matrix granules containing DCL which was covered on either side by guar gum granule layers containing either 70, 80 or 87% of guar gum as release retardant layers. The tablets were evaluated for hardness, thickness, drug content, and drug release studies. To ascertain the kinetics of drug release, the dissolution profiles were fitted to various mathematical models. The in vitro drug release from proposed system was best explained by the Hopfenberg model indicating that the release of drug from tablets displayed heterogeneous erosion. D3G3, containing 87% of guar gum in guar gum layers and 50% of guar gum in DCL matrix granule layer was found to provide the release rate for prolonged period of time. The results clearly indicate that guar gum could be a potential hydrophilic carrier in the development of oral controlled drug delivery systems. PMID:23181081

Granulation for Coking Wastewater Treatment in a Coupled Anaerobic-Aerobic Reactor

NASA Astrophysics Data System (ADS)

Dong, Chunjuan; Lv, Bingnan

2018-06-01

A coupled anaerobic-aerobic granular bio-film reactor was employed with two operation stages: Stage I, granular sludge was formed from digestion sludge using brewery wastewater, and Stage II, granular sludge was acclimatized using coking wastewater. Two oxygenation methods (i.e. A and B) were employed to acclimatize the granules. For method A, dissolved O 2 was supplied through a continuous oxygenation way of 800-15000ml-min-1 . And for method B, dissolved O2 was supplied of 800-15000ml-min-1 18-12 times at 20-60min intervals, 1h each time. The experimental results showed that granules could quickly form in 10d in the EGSB reactor seeded with digestion sludge and little loose granules lack of nutrition, and it was the key factor for granules forming to add little loose granules. It took only about 6 months for granules acclimation using coking wastewater. Both oxygenation methods could run well when acclimatizing the granules. However, method A could have comparatively high and stable operation effect. The actual coking wastewater had distinct inhibition effect on the granules, but the supplement of some oxygen could promote the recovery of SMA, and NaHCO3 supplement could also weaken the inhibition effect of the CWW. Method A had more strongly activity recovery ability than method B.

Particle Engineering of Excipients for Direct Compression: Understanding the Role of Material Properties.

PubMed

Mangal, Sharad; Meiser, Felix; Morton, David; Larson, Ian

2015-01-01

Tablets represent the preferred and most commonly dispensed pharmaceutical dosage form for administering active pharmaceutical ingredients (APIs). Minimizing the cost of goods and improving manufacturing output efficiency has motivated companies to use direct compression as a preferred method of tablet manufacturing. Excipients dictate the success of direct compression, notably by optimizing powder formulation compactability and flow, thus there has been a surge in creating excipients specifically designed to meet these needs for direct compression. Greater scientific understanding of tablet manufacturing coupled with effective application of the principles of material science and particle engineering has resulted in a number of improved direct compression excipients. Despite this, significant practical disadvantages of direct compression remain relative to granulation, and this is partly due to the limitations of direct compression excipients. For instance, in formulating high-dose APIs, a much higher level of excipient is required relative to wet or dry granulation and so tablets are much bigger. Creating excipients to enable direct compression of high-dose APIs requires the knowledge of the relationship between fundamental material properties and excipient functionalities. In this paper, we review the current understanding of the relationship between fundamental material properties and excipient functionality for direct compression.

Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

PubMed

Maejima, T; Kubo, M; Osawa, T; Nakajima, K; Kobayashi, M

1998-03-01

The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

The effect of process parameters on audible acoustic emissions from high-shear granulation.

PubMed

Hansuld, Erin M; Briens, Lauren; Sayani, Amyn; McCann, Joe A B

2013-02-01

Product quality in high-shear granulation is easily compromised by minor changes in raw material properties or process conditions. It is desired to develop a process analytical technology (PAT) that can monitor the process in real-time and provide feedback for quality control. In this work, the application of audible acoustic emissions (AAEs) as a PAT tool was investigated. A condenser microphone was placed at the top of the air exhaust on a PMA-10 high-shear granulator to collect AAEs for a design of experiment (DOE) varying impeller speed, total binder volume and spray rate. The results showed the 10 Hz total power spectral densities (TPSDs) between 20 and 250 Hz were significantly affected by the changes in process conditions. Impeller speed and spray rate were shown to have statistically significant effects on granulation wetting, and impeller speed and total binder volume were significant in terms of process end-point. The DOE results were confirmed by a multivariate PLS model of the TPSDs. The scores plot showed separation based on impeller speed in the first component and spray rate in the second component. The findings support the use of AAEs to monitor changes in process conditions in real-time and achieve consistent product quality.

Application of the combinative particle size reduction technology H 42 to produce fast dissolving glibenclamide tablets.

PubMed

Salazar, Jaime; Müller, Rainer H; Möschwitzer, Jan P

2013-07-16

Standard particle size reduction techniques such as high pressure homogenization or wet bead milling are frequently used in the production of nanosuspensions. The need for micronized starting material and long process times are their evident disadvantages. Combinative particle size reduction technologies have been developed to overcome the drawbacks of the standard techniques. The H 42 combinative technology consists of a drug pre-treatment by means of spray-drying followed by standard high pressure homogenization. In the present paper, spray-drying process parameters influencing the diminution effectiveness, such as drug and surfactant concentration, were systematically analyzed. Subsequently, the untreated and pre-treated drug powders were homogenized for 20 cycles at 1500 bar. For untreated, micronized glibenclamide, the particle size analysis revealed a mean particle size of 772 nm and volume-based size distribution values of 2.686 μm (d50%) and 14.423 μm (d90%). The use of pre-treated material (10:1 glibenclamide/docusate sodium salt ratio spray-dried as ethanolic solution) resulted in a mean particle size of 236 nm and volume-based size distribution values of 0.131 μm (d50%) and 0.285 μm (d90%). These results were markedly improved compared to the standard process. The nanosuspensions were further transferred into tablet formulations. Wet granulation, freeze-drying and spray-drying were investigated as downstream methods to produce dry intermediates. Regarding the dissolution rate, the rank order of the downstream processes was as follows: Spray-drying>freeze-drying>wet granulation. The best drug release (90% within 10 min) was obtained for tablets produced with spray-dried nanosuspension containing 2% mannitol as matrix former. In comparison, the tablets processed with micronized glibenclamide showed a drug release of only 26% after 10 min. The H 42 combinative technology could be successfully applied in the production of small drug nanocrystals. A nanosuspension transfer to tablets that maintained the fast dissolution properties of the drug nanocrystals was successfully achieved. Copyright © 2013 Elsevier B.V. All rights reserved.

Preparation of orally disintegrating tablets with taste-masking function: masking effect in granules prepared with correctives using the dry granulation method and evaluation of tablets prepared using the taste-masked granules.

PubMed

Kawano, Yayoi; Ito, Akihiko; Sasatsu, Masanaho; Machida, Yoshiharu

2010-01-01

We investigated several methods of taste masking in the preparation of orally disintegrating tablets (ODTs), using furosemide (FU) as a model drug. Four types of FU preparations were prepared: granules with maltitol (MA), granules with yogurt powder (YO), a physical mixture of FU and MA, and a physical mixture of FU and YO. All taste-masking granules were prepared using the dry granulation method. The taste of each type of preparation was evaluated. All four preparations markedly improved the taste of the FU tablets, but the mixing ratios of the correctives did not affect the masking effect. No difference in masking effect was found between MA and YO in the physical mixtures, but the masking effect in the granules with YO was superior to that of the granules with MA. Taste-masked FU tablets were prepared using the direct compression method; crystalline cellulose (Avicel PH-302) and mannitol were added as excipients at the mixing ratio of 1/1. All four types of tablets displayed sufficient hardness, but MA-containing tablets were harder than YO-containing tablets. The hardness of the tablets prepared from YO granules increased as the YO content increased. The most rapidly disintegrating tablets were those of YO granules prepared at a mixing ratio of FU/YO=1/1, which disintegrated within 20 s, followed by the tablets of MA granules prepared at a mixing ratio of FU/MA=1/1. The disintegration times of the tablets made from physical mixtures, in contrast, were longer than 200 s. Disintegration time lengthened as the mixing ratio of YO or MA increased. The hardness and disintegration time of these tablets could be controlled by varying the compression pressure. We found that YO is more useful than MA in masking unpleasant tastes and confirmed that orally disintegrating tablets with taste-masking function can be prepared using granules of YO prepared using the dry granulation method as a new corrective.

40 CFR 180.590 - 2, 6-Diisopropylnaphthalene (2, 6-DIPN); tolerances for residues.

Code of Federal Regulations, 2012 CFR

2012-07-01

... Parts per million Cattle, fat 0.2 Cattle, meat 0.02 Cattle, meat byproducts, except fat 0.02 Goat, fat 0.2 Goat, meat 0.02 Goat, meat byproducts, except fat 0.02 Horse, fat 0.2 Horse, meat 0.02 Horse, meat byproducts, except fat 0.02 Milk, fat 0.02 Potato, granules/flakes 5.5 Potato, wet peel 6.0 Potato, whole 2.0...

40 CFR 180.590 - 2, 6-Diisopropylnaphthalene (2, 6-DIPN); tolerances for residues.

Code of Federal Regulations, 2014 CFR

2014-07-01

... Parts per million Cattle, fat 0.2 Cattle, meat 0.02 Cattle, meat byproducts, except fat 0.02 Goat, fat 0.2 Goat, meat 0.02 Goat, meat byproducts, except fat 0.02 Horse, fat 0.2 Horse, meat 0.02 Horse, meat byproducts, except fat 0.02 Milk, fat 0.02 Potato, granules/flakes 5.5 Potato, wet peel 6.0 Potato, whole 2.0...

40 CFR 180.590 - 2, 6-Diisopropylnaphthalene (2, 6-DIPN); tolerances for residues.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Parts per million Cattle, fat 0.2 Cattle, meat 0.02 Cattle, meat byproducts, except fat 0.02 Goat, fat 0.2 Goat, meat 0.02 Goat, meat byproducts, except fat 0.02 Horse, fat 0.2 Horse, meat 0.02 Horse, meat byproducts, except fat 0.02 Milk, fat 0.02 Potato, granules/flakes 5.5 Potato, wet peel 6.0 Potato, whole 2.0...

[Molecular authentication of Jinyinhua formula granule by using allele-specific PCR].

PubMed

Jiang, Chao; Tu, Li-Chan; Yuan, Yuan; Huang, Lu-Qi; Gao, Wei; Jin, Yan

2017-07-01

Traditional authentication method is hard to identify herb's authenticity of traditional Chinese medicine(TCM) formula granules because they have lost all their morphological characteristics. In this study, a new allele-specific PCR method was established for identifying the authentication of Jinyinhua formula granule (made from Lonicerae Japonicae Flos) based on an SNP site in trnL-trnF fragment. Genomic DNA was successfully extracted from Lonicerae Japonicae Flos and its formula granules by using an improved spin column method and then PCR was performed with the designed primer. Approximately 110 bp specific bands was obtained only in the authentic Lonicerae Japonicae Flos and its formula granules, while no bands were found in fake mixed products. In addition, the PCR product sequence was proved from Lonicerae Japonicae Flos trnL-trnF sequence by using BLAST method. Therefore, DNA molecular authentication method could make up the limitations of character identification method and microscopic identification, and quickly identify herb's authenticity of TCM formula granules, with enormous potential for market supervision and quality control. Copyright© by the Chinese Pharmaceutical Association.

Hardened, environmentally disposable composite granules of coal cleaning refuse, coal combustion waste, and other wastes, and method preparing the same

DOEpatents

Burnet, George; Gokhale, Ashok J.

1990-07-10

A hardened, environmentally inert and disposable composite granule of coal cleaning refuse and coal combustion waste, and method for producing the same, wherein the coal combustion waste is first granulated. The coal cleaning refuse is pulverized into fine particles and is then bound, as an outer layer, to the granulated coal combustion waste granules. This combination is then combusted and sintered. After cooling, the combination results in hardened, environmentally inert and disposable composite granules having cores of coal combustion waste, and outer shells of coal cleaning refuse. The composite particles are durable and extremely resistant to environmental and chemical forces.

Hardened, environmentally disposable composite granules of coal cleaning refuse, coal combustion waste, and other wastes, and method preparing the same

DOEpatents

Burnet, G.; Gokhale, A.J.

1990-07-10

A hardened, environmentally inert and disposable composite granule of coal cleaning refuse and coal combustion waste and method for producing the same are disclosed, wherein the coal combustion waste is first granulated. The coal cleaning refuse is pulverized into fine particles and is then bound, as an outer layer, to the granulated coal combustion waste granules. This combination is then combusted and sintered. After cooling, the combination results in hardened, environmentally inert and disposable composite granules having cores of coal combustion waste, and outer shells of coal cleaning refuse. The composite particles are durable and extremely resistant to environmental and chemical forces. 3 figs.

Influence of formulation technique on acrylate methacrylate copolymer modified paracetamol matrix tablets.

PubMed

Cash-Torunarigha, Omonyemen Edoise; Eichie, Florence Egbomonjiade; Arhewoh, Matthew Ikhuoria

2015-03-01

This work was designed to evaluate the influence of various methods such as dry granulation (DG), wet granulation (using the polymer in an ethanolic solution (WGO) or aqueous dispersion (WGA) and solid dispersion (SD) techniques, on properties of paracetamol matrix tablets prepared using varying concentrations of acrylate methacrylate copolymer. Tablet properties were investigated using official and unofficial standards. Drug dissolution profile assessed at pH 1.2 was studied spectrophotometrically at λ(max) of 245 nm. With the use of various kinetic models, the release mechanism of the drug was analyzed. The parameters, maximum amount of drug release (m(∞)) at time t(∞) were obtained, m(∞) was ≥ 91.36 %, while t(∞) was ≥ 4.5 h. The release rate constant (k) for DG tablets was 15.61 h(sup>-1(/sup>, while, WGO, WGA and SD tablets were 12.90, 11.03 and 10.75 h(-1) respectively. The matrix tablets, which exhibited marked retardation in drug release displayed a Higuchi square root of time model (R(2) > 0.98). The mechanism through which the drug was released was governed by Fickian diffusion release (n values < 0.5). The performance of the drug was affected by the formulation technique in the order of SD > WGO > WGA > DG.

Methods of synthesizing hydroxyapatite powders and bulk materials

DOEpatents

Luo, Ping

1999-01-12

Methods are provided for producing non-porous controlled morphology hydroxyapatite granules of less than 8 .mu.m by a spray-drying process. Solid or hollow spheres or doughnuts can be formed by controlling the volume fraction and viscosity of the slurry as well as the spray-drying conditions. Methods of providing for homogenous cellular structure hydroxyapatite granules are also provided. Pores or channels or varying size and number can be formed by varying the temperature at which a hydroxyapatite slurry formed in basic, saturated ammonium hydroxide is spray-dried. Methods of providing non-porous controlled morphology hydroxyapatite granules in ammonium hydroxide are also provided. The hydroxyapatite granules and bulk materials formed by these methods are also provided.

Methods of synthesizing hydroxyapatite powders and bulk materials

DOEpatents

Luo, P.

1999-01-12

Methods are provided for producing non-porous controlled morphology hydroxyapatite granules of less than 8 {micro}m by a spray-drying process. Solid or hollow spheres or doughnuts can be formed by controlling the volume fraction and viscosity of the slurry as well as the spray-drying conditions. Methods of providing for homogeneous cellular structure hydroxyapatite granules are also provided. Pores or channels or varying size and number can be formed by varying the temperature at which a hydroxyapatite slurry formed in basic, saturated ammonium hydroxide is spray-dried. Methods of providing non-porous controlled morphology hydroxyapatite granules in ammonium hydroxide are also provided. The hydroxyapatite granules and bulk materials formed by these methods are also provided. 26 figs.

Investigation of internal structure of fine granules by microtomography using synchrotron X-ray radiation.

PubMed

Noguchi, Shuji; Kajihara, Ryusuke; Iwao, Yasunori; Fujinami, Yukari; Suzuki, Yoshio; Terada, Yasuko; Uesugi, Kentaro; Miura, Keiko; Itai, Shigeru

2013-03-10

Computed tomography (CT) using synchrotron X-ray radiation was evaluated as a non-destructive structural analysis method for fine granules. Two kinds of granules have been investigated: a bromhexine hydrochloride (BHX)-layered Celphere CP-102 granule coated with pH-sensitive polymer Kollicoat Smartseal 30-D, and a wax-matrix granule constructed from acetaminophen (APAP), dibasic calcium phosphate dehydrate, and aminoalkyl methacrylate copolymer E (AMCE) manufactured by melt granulation. The diameters of both granules were 200-300 μm. CT analysis of CP-102 granule could visualize the laminar structures of BHX and Kollicoat layers, and also visualize the high talc-content regions in the Kollicoat layer that could not be detected by scanning electron microscopy. Moreover, CT analysis using X-ray energies above the absorption edge of Br specifically enhanced the contrast in the BHX layer. As for granules manufactured by melt granulation, CT analysis revealed that they had a small inner void space due to a uniform distribution of APAP and other excipients. The distribution of AMCE revealed by CT analysis was also found to involve in the differences of drug dissolution from the granules as described previously. These observations demonstrate that CT analysis using synchrotron X-ray radiation is a powerful method for the detailed internal structure analysis of fine granules. Copyright © 2013 Elsevier B.V. All rights reserved.

Osteogenic efficacy of strontium hydroxyapatite micro-granules in osteoporotic rat model.

PubMed

Chandran, Sunitha; Babu S, Suresh; Vs, Hari Krishnan; Varma, H K; John, Annie

2016-10-01

Excessive demineralization in osteoporotic bones impairs its self-regeneration potential following a defect/fracture and is of great concern among the aged population. In this context, implants with inherent osteogenic ability loaded with therapeutic ions like Strontium (Sr 2+ ) may bring forth promising outcomes. Micro-granular Strontium incorporated Hydroxyapatite scaffolds have been synthesized and in vivo osteogenic efficacy was evaluated in a long-term osteoporosis-induced aged (LOA) rat model. Micro-granules with improved surface area are anticipated to resorb faster and together with the inherent bioactive properties of Hydroxyapatite with the leaching of Strontium ions from the scaffold, osteoporotic bone healing may be promoted. Long-term osteoporosis-induced aged rat model was chosen to extrapolate the results to clinical osteoporotic condition in the aged. Micro-granular 10% Strontium incorporated Hydroxyapatite synthesized by wet precipitation method exhibited increased in vitro dissolution rate and inductively coupled plasma studies confirmed Strontium ion release of 0.01 mM, proving its therapeutic potential for osteoporotic applications. Wistar rats were induced to long-term osteoporosis-induced aged model by ovariectomy along with a prolonged induction period of 10 months. Thereafter, osteogenic efficacy of Strontium incorporated Hydroxyapatite micro-granules was evaluated in femoral bone defects in the long-term osteoporosis-induced aged model. Post eight weeks of implantation in vivo regeneration efficacy ratio was highest in the Strontium incorporated Hydroxyapatite implanted group (0.92 ± 0.04) compared to sham and Hydroxyapatite implanted group. Micro CT evaluation further substantiated the improved osteointegration of Strontium incorporated Hydroxyapatite implants from the density histograms. Thus, the therapeutical potential of micro-granular Strontium incorporated Hydroxyapatite scaffolds becomes relevant, especially as bone void fillers in osteoporotic cases of tumor resection or trauma. © The Author(s) 2016.

Detection of component segregation in granules manufactured by high shear granulation with over-granulation conditions using near-infrared chemical imaging.

PubMed

Koide, Tatsuo; Nagato, Takuya; Kanou, Yoshiyuki; Matsui, Kou; Natsuyama, Susumu; Kawanishi, Toru; Hiyama, Yukio

2013-01-30

The objective of this study was to evaluate the high shear granulation process using near-infrared (NIR) chemical imaging technique and to make the findings available for pharmaceutical development. We prepared granules and tablets made under appropriate- and over-granulation conditions with high shear granulation and observed these granules and tablets using NIR chemical imaging system. We found an interesting phenomenon: lactose agglomeration and segregation of ingredients occurred in experimental tablets when over-granulation conditions, including greater impeller rotation speeds and longer granulation times, were employed. Granules prepared using over-granulation conditions were larger and had progressed to the consolidation stage; segregation between ethenzamide and lactose occurred within larger granules. The segregation observed here is not detectable using conventional analytical technologies such as high pressure liquid chromatography (HPLC) because the content of the granules remained uniform despite the segregation. Therefore, granule visualization using NIR chemical imaging is an effective method for investigating and evaluating the granulation process. Copyright © 2012 Elsevier B.V. All rights reserved.

Effects of mild hyperthyroidism on levels of amino acids in the developing Lurcher cerebellum.

PubMed

Messer, A; Eisenberg, B; Martin, D L

1989-01-01

This study examines the question of whether intrinsically defective mutant Lurcher Purkinje cells, which degenerate during postnatal weeks two to five, followed by later loss of granule cells are competent to respond to neonatal hyperthyroidism, which is known to cause premature differentiation of Purkinje cells and an acceleration of the peak of proliferation in granule cells in normal rodent cerebellum. Both total amounts and concentrations (per mg wet weight) of Tau, Glu, Asp and GABA were assayed as markers of cell function in Lurcher and wild-type mice made very mildly hyperthyroid by feeding nursing dams high-thyroxine food. Tau, which is present in relatively high concentrations in Purkinje cells, was affected by hyperthyroid treatment in the Lurcher in a manner that is most consistent with an acceleration of the degenerative process in Purkinje cells. The acidic amino acids Glu and Asp show later changes and response to hormone which seem to be a reaction to the Purkinje cell pattern, probably in the granule cells. We conclude that the Lurcher cerebellum is particularly sensitive to thyroid hormone, and that it responds to low levels of hyperthyroidism in a distinct way.

Design and evaluation of effervescent floating tablets based on hydroxyethyl cellulose and sodium alginate using pentoxifylline as a model drug

PubMed Central

Rahim, Safwan Abdel; Carter, Paul A; Elkordy, Amal Ali

2015-01-01

The aim of this work was to design and evaluate effervescent floating gastro-retentive drug delivery matrix tablets with sustained-release behavior using a binary mixture of hydroxyethyl cellulose and sodium alginate. Pentoxifylline was used as a highly water-soluble, short half-life model drug with a high density. The floating capacity, swelling, and drug release behaviors of drug-loaded matrix tablets were evaluated in 0.1 N HCl (pH 1.2) at 37°C±0.5°C. Release data were analyzed by fitting the power law model of Korsmeyer–Peppas. The effect of different formulation variables was investigated, such as wet granulation, sodium bicarbonate gas-forming agent level, and tablet hardness properties. Statistical analysis was applied by paired sample t-test and one-way analysis of variance depending on the type of data to determine significant effect of different parameters. All prepared tablets through wet granulation showed acceptable physicochemical properties and their drug release profiles followed non-Fickian diffusion. They could float on the surface of dissolution medium and sustain drug release over 24 hours. Tablets prepared with 20% w/w sodium bicarbonate at 50–54 N hardness were promising with respect to their floating lag time, floating duration, swelling ability, and sustained drug release profile. PMID:25848220

Lewis M. Rutherfurd and the First Photograph of Solar Granulation

NASA Astrophysics Data System (ADS)

Harvey, J. W.; Briggs, John W.; Prosser, Sian

2017-08-01

A major astronomical controversy of the mid-19th century was discordant descriptions of the small scale structure of the solar surface. Visual observers contradicted each other by describing the surface as consisting of “corrugations”, “willow leaves”, “rice grains”, “cumuli”, “thatch”, “granules”, etc. Early photographs of the solar surface were not good enough to settle the controversy. The French astronomer Jules Janssen is credited with the first 1876 photographs that clearly showed what we now call solar granulation (1876, CRAS 82, 1363). Upon seeing these images, New Yorker Lewis M. Rutherfurd (1878, MNRAS 38, 410) praised the high quality of Janssen’s images but asserted that he had also photographed granulation as early as 1871 using collodion wet plates. He sent copies of his best photograph to the Royal Astronomical Society to support his assertion. Curious about his claim, Briggs and Harvey set up Rutherfurd’s 13-inch achromatic refractor on Kitt Peak and found that it easily showed well-resolved solar granulation, so his claim might well have been justified. But without his plates we could not confirm the claim. For 140 years the copies of Rutherfurd’s best solar photograph remained in the archives of the Royal Astronomical Society and were recently discovered by Prosser (RAS Photographs A3/001B and A3/002). By coincidence a few days later, Briggs found the original August 11, 1871 plate. Despite poor condition these photographs show solar granulation. There are at least two other possible early claimants (Reade; Vogel) but their plates are almost certainly lost. Rutherfurd was a master of astronomical instrumentation and photography. He was reticent about his work, letting results speak for themselves, so it is satisfying to find that he was justified in making his claim of priority.

Development and in vitro evaluation of carboxymethyl chitosan based drug delivery system for the controlled release of propranolol hydrochloride

NASA Astrophysics Data System (ADS)

Hernawan; Nur Hayati, Septi; Nisa, Khoirun; Wheni Indrianingsih, Anastasia; Darsih, Cici; Kismurtono, Muhammad

2017-12-01

Propranolol hydrochloride is a nonselective β-adrenergic drug and has been used as angina pectoris, antihypertensive, and that of many other cardiovascular disorders. It has a relatively short plasma half-life and duration of action are considered too short in certain circumstances. Thus, it’s fascinating to elongate the action. The tablet formula was based on extended-release by a propranolol hydrochloride based carboxymethyl chitosan matrix. Here we used direct compression technique with internal wet granulation to prepare the tablets. The tablets were evaluated for physical properties (hardness, weight variation test, friability) and in vitro release studies. There was no interaction observed between propranolol hydrochloride and excipients. Dissolution profiles of each formulation were followed zero order model. In conclusion, these results strongly suggest that in appropriate proportions carboxymethyl chitosan with internal granulation is suitable for formulating propranolol hydrochloride controlled release.

Application of quality by design concepts in the development of fluidized bed granulation and tableting processes.

PubMed

Djuris, Jelena; Medarevic, Djordje; Krstic, Marko; Djuric, Zorica; Ibric, Svetlana

2013-06-01

This study illustrates the application of experimental design and multivariate data analysis in defining design space for granulation and tableting processes. According to the quality by design concepts, critical quality attributes (CQAs) of granules and tablets, as well as critical parameters of granulation and tableting processes, were identified and evaluated. Acetaminophen was used as the model drug, and one of the study aims was to investigate the possibility of the development of immediate- or extended-release acetaminophen tablets. Granulation experiments were performed in the fluid bed processor using polyethylene oxide polymer as a binder in the direct granulation method. Tablets were compressed in the laboratory excenter tablet press. The first set of experiments was organized according to Plackett-Burman design, followed by the full factorial experimental design. Principal component analysis and partial least squares regression were applied as the multivariate analysis techniques. By using these different methods, CQAs and process parameters were identified and quantified. Furthermore, an in-line method was developed to monitor the temperature during the fluidized bed granulation process, to foresee possible defects in granules CQAs. Various control strategies that are based on the process understanding and assure desired quality attributes of the product are proposed. Copyright © 2013 Wiley Periodicals, Inc.

Evaluating the interaction of a tracheobronchial stent in an ovine in-vivo model.

PubMed

McGrath, Donnacha J; Thiebes, Anja Lena; Cornelissen, Christian G; O'Brien, Barry; Jockenhoevel, Stefan; Bruzzi, Mark; McHugh, Peter E

2018-04-01

Tracheobronchial stents are used to restore patency to stenosed airways. However, these devices are associated with many complications such as stent migration, granulation tissue formation, mucous plugging and stent strut fracture. Of these, granulation tissue formation is the complication that most frequently requires costly secondary interventions. In this study a biomechanical lung modelling framework recently developed by the authors to capture the lung in-vivo stress state under physiological loading is employed in conjunction with ovine pre-clinical stenting results and device experimental data to evaluate the effect of stent interaction on granulation tissue formation. Stenting is simulated using a validated model of a prototype covered laser-cut tracheobronchial stent in a semi-specific biomechanical lung model, and physiological loading is performed. Two computational methods are then used to predict possible granulation tissue formation: the standard method which utilises the increase in maximum principal stress change, and a newly proposed method which compares the change in contact pressure over a respiratory cycle. These computational predictions of granulation tissue formation are then compared to pre-clinical stenting observations after a 6-week implantation period. Experimental results of the pre-clinical stent implantation showed signs of granulation tissue formation both proximally and distally, with a greater proximal reaction. The standard method failed to show a correlation with the experimental results. However, the contact change method showed an apparent correlation with granulation tissue formation. These results suggest that this new method could be used as a tool to improve future device designs.

Distribution of a viscous binder during high shear granulation--sensitivity to the method of delivery and its impact on product properties.

PubMed

Tan, Bernice Mei Jin; Loh, Zhi Hui; Soh, Josephine Lay Peng; Liew, Celine Valeria; Heng, Paul Wan Sia

2014-01-02

Binder distribution in the powder mass during high shear granulation is especially critical with the use of viscous liquid binders and with short processing times. A viscous liquid binder was delivered into the powder mass at two flow rates using three methods: pouring, pumping and spraying from a pressure pot. Binder content analyses at the scale of individual granules were conducted to investigate the impact of different delivery conditions on the homogeneity of binder distribution. There was clear evidence of non-uniformity of binder content among individual granules across all delivery conditions, particularly for the fast rates of delivery. Poorer reproducibility values of tablet thickness and disintegration time were observed when binder was poured but this may be overcome by pumping or spraying from the pressure pot. Greater homogeneity of binder distribution occurred with the slow rates of delivery and led to the earlier onset of granule growth and a consequent increase in granule size. Larger granule size and lower proportion of fines were in turn associated with increased granule bulk density and improvement of granule flow. In conclusion, delivery of a viscous binder at a slow rate either by pumping or via a pressure pot was most desirable during granulation. Copyright © 2013 Elsevier B.V. All rights reserved.

Zero-order release of aspirin, theophylline and atenolol in water from novel methylcellulose glutarate matrix tablets.

PubMed

Khairuzzaman, A; Ahmed, S U; Savva, M; Patel, N K

2006-08-02

A novel hydrocolloidal polymer, methylcellulose glutarate (MC-GA), was prepared by esterifying methylcellulose with glutaric anhydride. The formation of ester was confirmed by FTIR and NMR spectroscopy, DSC and elemental analysis. The physicochemical properties such as, rate of swelling in water, viscosity and hygroscopicity of MC-GA were determined and compared with those of methycellulose A (MC). Aspirin, theophylline and atenolol tablets were compacted on a Carver press using the wet granulation method. Each tablet contained: 200 mg active, 80 mg anhydrous lactose, 8 mg povidone, 4 mg magnesium stearate, 4 mg talc, 50mg MC or MC-GA (drug-to-polymer ratio, 4:1). Contrary to the first-order release profile of all the drugs from the MC matrix tablets, a zero-order release was obtained from the MC-GA matrix tablets in water.

Determination of hydrophobicity of dry-heated wheat starch granules using sucrose fatty acid esters (SFAE).

PubMed

Tabara, Aya; Oneda, Hiroshi; Murayama, Ryuji; Matsui, Yuko; Hirano, Akira; Seguchi, Masaharu

2014-01-01

Sucrose fatty acid esters (SFAE) were adsorbed onto dry-heated (120 °C for 10, 20, 40, 60, and 120 min) wheat starch granules and extracted with ethyl ether in a Soxhlet apparatus without gelatinization of the starch granules. The amount of sucrose in the extracted SFAE was determined by the phenol sulfate method. A gradual increase of the sucrose from 159 to 712 μg, in SFAE per gram of starch, occurred with increasing dry-heating time and demonstrated the increased hydrophobicity of the starch granules. Increase of the SFAE was highly correlated (r = 0.9816) to increase of the oil-binding capacity of the dry-heated wheat starch granules. Non-waxy rice, waxy rice, sweet potato, and potato starch granules also showed higher hydrophobicity after dry-heating by this method.

A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

PubMed

Kubota, Kenta; Seno, Takeshi; Konishi, Yoshiyuki

2013-11-20

Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis. © 2013 Elsevier B.V. All rights reserved.

Proteome Profile of Starch Granules Purified from Rice (Oryza sativa) Endosperm.

PubMed

Xing, Shihai; Meng, Xiaoxi; Zhou, Lihui; Mujahid, Hana; Zhao, Chunfang; Zhang, Yadong; Wang, Cailin; Peng, Zhaohua

2016-01-01

Starch is the most important food energy source in cereals. Many of the known enzymes involved in starch biosynthesis are partially or entirely granule-associated in the endosperm. Studying the proteome of rice starch granules is critical for us to further understand the mechanisms underlying starch biosynthesis and packaging of starch granules in rice amyloplasts, consequently for the improvement of rice grain quality. In this article, we developed a protocol to purify starch granules from mature rice endosperm and verified the quality of purified starch granules by microscopy observations, I2 staining, and Western blot analyses. In addition, we found the phenol extraction method was superior to Tris-HCl buffer extraction method with respect to the efficiency in recovery of starch granule associated proteins. LC-MS/MS analysis showed identification of already known starch granule associated proteins with high confidence. Several proteins reported to be involved in starch synthesis in prior genetic studies in plants were also shown to be enriched with starch granules, either directly or indirectly, in our studies. In addition, our results suggested that a few additional candidate proteins may also be involved in starch synthesis. Furthermore, our results indicated that some starch synthesis pathway proteins are subject to protein acetylation modification. GO analysis and KEGG pathway enrichment analysis showed that the identified proteins were mainly located in plastids and involved in carbohydrate metabolism. This study substantially advances the understanding of the starch granule associated proteome in rice and post translational regulation of some starch granule associated proteins.

Physical, electrochemical, and thermal properties of granulated natural graphite as anodes for Li-ion batteries.

PubMed

Jo, Yong Nam; Park, Min-Sik; Kim, Jae-Hun; Kim, Young-Jun

2013-05-01

Two different types of granulated graphites were synthesized by blending and kneading of natural graphite with pitch followed by sintering methods. The electrochemical performances of granulated graphites were investigated as anode materials for use in Li-ion batteries. The blending type granulated graphite possesses a large amount of cavities and voids, while the kneading type granulated graphite has a relatively compact microstructure, which is responsible for a high tap density. Both granulated graphites show improved the initial coulombic efficiencies as a result of decrease of surface area by the granulations. In particular, the kneading type granulated graphite exhibits an excellent rate-capability without significant capacity loss. In addition, the thermal stabilities of both granulated graphites were also improved, which could be attributed to the decrease of active surface area due to pitch coating.

Blend uniformity evaluation during continuous mixing in a twin screw granulator by in-line NIR using a moving F-test.

PubMed

Fonteyne, Margot; Vercruysse, Jurgen; De Leersnyder, Fien; Besseling, Rut; Gerich, Ad; Oostra, Wim; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

2016-09-07

This study focuses on the twin screw granulator of a continuous from-powder-to-tablet production line. Whereas powder dosing into the granulation unit is possible from a container of preblended material, a truly continuous process uses several feeders (each one dosing an individual ingredient) and relies on a continuous blending step prior to granulation. The aim of the current study was to investigate the in-line blending capacity of this twin screw granulator, equipped with conveying elements only. The feasibility of in-line NIR (SentroPAT, Sentronic GmbH, Dresden, Germany) spectroscopy for evaluating the blend uniformity of powders after the granulator was tested. Anhydrous theophylline was used as a tracer molecule and was blended with lactose monohydrate. Theophylline and lactose were both fed from a different feeder into the twin screw granulator barrel. Both homogeneous mixtures and mixing experiments with induced errors were investigated. The in-line spectroscopic analyses showed that the twin screw granulator is a useful tool for in-line blending in different conditions. The blend homogeneity was evaluated by means of a novel statistical method being the moving F-test method in which the variance between two blocks of collected NIR spectra is evaluated. The α- and β-error of the moving F-test are controlled by using the appropriate block size of spectra. The moving F-test method showed to be an appropriate calibration and maintenance free method for blend homogeneity evaluation during continuous mixing. Copyright © 2016 Elsevier B.V. All rights reserved.

Water hyacinth: a possible alternative rate retarding natural polymer used in sustained release tablet design

PubMed Central

Khatun, Sabera; Sutradhar, Kumar B.

2014-01-01

In recent years natural polymers have been widely used because of their effectiveness and availability over synthetic polymers. In this present investigation matrix tablets of Metformin hydrochloride were formulated using Water hyacinth powder and its rate retardant activity was studied. Tablets were prepared using wet granulation method with 8% starch as granulating agent and 5, 10, 15, 20, 25 and 30% of Water hyacinth powder to the drug. In preformulation study, angle of repose, Carr's Index and Hausner ratio were calculated. Fourier Transform Infrared Spectroscopy (FTIR), Differential Scanning Calorimetry (DSC), and Scanning Electron Microscopy (SEM) studies were performed and no interactions were found between drug and excipients. Weight variation, friability, hardness, thickness, diameter, and in vitro release study were performed with the prepared matrix tablets. Dissolution studies were conducted using USP type II apparatus at a speed of 100 rpm at 37°C ± 0.5 temperature for 8 h. Though all the formulations comply with both BP and USP requirements, formulation F-1 (5% of Water hyacinth) was the best fitted formula. The drug release patterns were explained in different kinetic models such as Zero order, First order, Higuchi, Hixson Crowell, and Korsmeyer-Peppas equations. The current investigation implies that Water hyacinth has the potential to be used as a rate-retarding agent in sustained release drug formulations. PMID:24966835

A novel solid dosage form of rifampicin and isoniazid with improved functionality.

PubMed

Gohel, Mukesh C; Sarvaiya, Krishnakant G

2007-08-24

The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.

[Key physical parameters of hawthorn leaf granules by stepwise regression analysis method].

PubMed

Jiang, Qie-Ying; Zeng, Rong-Gui; Li, Zhe; Luo, Juan; Zhao, Guo-Wei; Lv, Dan; Liao, Zheng-Gen

2017-05-01

The purpose of this study was to investigate the effect of key physical properties of hawthorn leaf granule on its dissolution behavior. Hawthorn leaves extract was utilized as a model drug. The extract was mixed with microcrystalline cellulose or starch with the same ratio by using different methods. Appropriate amount of lubricant and disintegrating agent was added into part of the mixed powder, and then the granules were prepared by using extrusion granulation and high shear granulation. The granules dissolution behavior was evaluated by using equilibrium dissolution quantity and dissolution rate constant of the hypericin as the indicators. Then the effect of physical properties on dissolution behavior was analyzed through the stepwise regression analysis method. The equilibrium dissolution quantity of hypericin and adsorption heat constant in hawthorn leaves were positively correlated with the monolayer adsorption capacity and negatively correlated with the moisture absorption rate constant. The dissolution rate constants were decreased with the increase of Hausner rate, monolayer adsorption capacity and adsorption heat constant, and were increased with the increase of Carr index and specific surface area. Adsorption heat constant, monolayer adsorption capacity, moisture absorption rate constant, Carr index and specific surface area were the key physical properties of hawthorn leaf granule to affect its dissolution behavior. Copyright© by the Chinese Pharmaceutical Association.

Proteome Profile of Starch Granules Purified from Rice (Oryza sativa) Endosperm

PubMed Central

Xing, Shihai; Meng, Xiaoxi; Zhou, Lihui; Mujahid, Hana; Zhao, Chunfang; Zhang, Yadong; Wang, Cailin; Peng, Zhaohua

2016-01-01

Starch is the most important food energy source in cereals. Many of the known enzymes involved in starch biosynthesis are partially or entirely granule-associated in the endosperm. Studying the proteome of rice starch granules is critical for us to further understand the mechanisms underlying starch biosynthesis and packaging of starch granules in rice amyloplasts, consequently for the improvement of rice grain quality. In this article, we developed a protocol to purify starch granules from mature rice endosperm and verified the quality of purified starch granules by microscopy observations, I2 staining, and Western blot analyses. In addition, we found the phenol extraction method was superior to Tris-HCl buffer extraction method with respect to the efficiency in recovery of starch granule associated proteins. LC-MS/MS analysis showed identification of already known starch granule associated proteins with high confidence. Several proteins reported to be involved in starch synthesis in prior genetic studies in plants were also shown to be enriched with starch granules, either directly or indirectly, in our studies. In addition, our results suggested that a few additional candidate proteins may also be involved in starch synthesis. Furthermore, our results indicated that some starch synthesis pathway proteins are subject to protein acetylation modification. GO analysis and KEGG pathway enrichment analysis showed that the identified proteins were mainly located in plastids and involved in carbohydrate metabolism. This study substantially advances the understanding of the starch granule associated proteome in rice and post translational regulation of some starch granule associated proteins. PMID:27992503

New multifunctional pharmaceutical excipient in tablet formulation based on citric acid-cyclodextrin polymer.

PubMed

Garcia-Fernandez, Maria José; Tabary, Nicolas; Chai, Feng; Cazaux, Frédéric; Blanchemain, Nicolas; Flament, Marie-Pierre; Martel, Bernard

2016-09-25

A β-cyclodextrin (β-CD) polymer obtained by crosslinking β-CD with citric acid in its water-insoluble (PCD-I) and soluble (PCD-S) forms was used as a multifunctional direct compression excipient for tablet designing. PCD-I powder was obtained after grinding the solid fraction through a 200μm grid. PCD-S powder was recovered after lyophilization or spray drying of the PCD-S aqueous solutions, eventually followed by a wet granulation step. Both PCD-I and PCD-S powders were characterized, separately and mixed in variable ratios, based on dynamic water vapor sorption, SEM, particle size distribution, tapped density, compressibility, and flowability. PCD-I and spray dried and lyophilized/wet granulated PCD-S, as well as the mixture PCD-I/PCD-S=90/10, presented optimal free flowing characteristics. Then, PCD-I or PCD-S powders - separately or mixed in variable ratios - were used for tablets preparation by direct compression without adding any other excipient (e.g. binder, lubricant, disintegrant etc). As PCD-I decreased, tablets resistance to crushing and disintegration time increased from 15s to 15min (against 30min for β-CD), showing the improved disintegrant functionality of PCD-I, that rapidly swelled once in contact with water. Finally, PCD was force-fed to Sprague-Dawley rats (2g/kg) which were then observed during 14days for any clinical signs of toxicity. Copyright © 2016. Published by Elsevier B.V.

Melt Adsorption as a Manufacturing Method for Fine Particles of Wax Matrices without Any Agglomerates.

PubMed

Shiino, Kai; Fujinami, Yukari; Kimura, Shin-Ichiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

2017-01-01

We have focused on melt adsorption as manufacture method of wax matrices to control particles size of granules more easily than melt granulation. The purpose of present study was to investigate the possibility of identifying a hydrophobic material with a low melting point, currently used as a meltable binder of melt granulation, to apply as a novel carrier in melt adsorption. Glyceryl monostearate (GM) and stearic acid (SA) were selected as candidate hydrophobic materials with low melting points. Neusilin US2 (US2), with a particle diameter of around 100 µm was selected as a surface adsorbent, while dibasic calcium phosphate dihydrate (DCPD), was used as a non-adsorbent control to prepare melting granules as a standard for comparison. We prepared granules containing ibuprofen (IBU) by melt adsorption or melt granulation and evaluated the particle size, physical properties and crystallinity of granules. Compared with melt granulation using DCPD, melt adsorption can be performed over a wide range of 14 to 70% for the ratio of molten components. Moreover, the particle size; d50 of obtained granules was 100-200 µm, and these physical properties showed good flowability and roundness. The process of melt adsorption did not affect the crystalline form of IBU. Therefore, the present study has demonstrated for the first time that melt adsorption using a hydrophobic material, GM or SA, has the potential capability to control the particle size of granules and offers the possibility of application as a novel controlled release technique.

Crystallization and initial X-ray analysis of polyhydroxyalkanoate granule-associated protein from Aeromonas hydrophila

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, Minglian; Li, Zhenguo; Zheng, Wei

The phasin PhaP{sub Ah} from A. hydrophila strain 4AK4 was crystallized using the hanging-drop vapour-diffusion method. Polyhydroxyalkanoate (PHA) granule-associated proteins (phasins) were discovered in PHA-accumulating bacteria. They play a crucial role as a structural protein during initial PHA-granule formation and granule growth and also serve as interfaces for granule stabilization in vivo. The phasin PhaP{sub Ah} from Aeromonas hydrophila strain 4AK4 was crystallized using the hanging-drop vapour-diffusion method. Single crystals were cryocooled for X-ray diffraction analysis. The phasin crystals belonged to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 80.8, b = 108.9, c = 134.4 Å.

Isolation of zymogen granules from rat pancreas.

PubMed

Rindler, Michael J

2006-01-01

This unit describes methods for preparing zymogen granules from rat pancreas. Zymogen granules are storage organelles in pancreatic acinar cells containing digestive enzymes that are released into the pancreatic duct. The protocols in this unit take advantage of the large size (up to 1 microm diameter) and high density (>1.20 g/cm(3) on sucrose gradients) of the granules as compared to other cellular organelles. They use a combination of differential sedimentation and density gradient separation to accomplish the purification. Similar procedures can be used to isolate zymogen granules from mouse pancreas and canine pancreas. A protocol for preparing zymogen granules from dog pancreas is also included.

An improved approach for the segmentation of starch granules in microscopic images

PubMed Central

2010-01-01

Background Starches are the main storage polysaccharides in plants and are distributed widely throughout plants including seeds, roots, tubers, leaves, stems and so on. Currently, microscopic observation is one of the most important ways to investigate and analyze the structure of starches. The position, shape, and size of the starch granules are the main measurements for quantitative analysis. In order to obtain these measurements, segmentation of starch granules from the background is very important. However, automatic segmentation of starch granules is still a challenging task because of the limitation of imaging condition and the complex scenarios of overlapping granules. Results We propose a novel method to segment starch granules in microscopic images. In the proposed method, we first separate starch granules from background using automatic thresholding and then roughly segment the image using watershed algorithm. In order to reduce the oversegmentation in watershed algorithm, we use the roundness of each segment, and analyze the gradient vector field to find the critical points so as to identify oversegments. After oversegments are found, we extract the features, such as the position and intensity of the oversegments, and use fuzzy c-means clustering to merge the oversegments to the objects with similar features. Experimental results demonstrate that the proposed method can alleviate oversegmentation of watershed segmentation algorithm successfully. Conclusions We present a new scheme for starch granules segmentation. The proposed scheme aims to alleviate the oversegmentation in watershed algorithm. We use the shape information and critical points of gradient vector flow (GVF) of starch granules to identify oversegments, and use fuzzy c-mean clustering based on prior knowledge to merge these oversegments to the objects. Experimental results on twenty microscopic starch images demonstrate the effectiveness of the proposed scheme. PMID:21047380

Orodispersible tablets: A new trend in drug delivery

PubMed Central

Dey, Paramita; Maiti, Sabyasachi

2010-01-01

The most common and preferred route of drug administration is through the oral route. Orodispersible tablets are gaining importance among novel oral drug-delivery system as they have improved patient compliance and have some additional advantages compared to other oral formulation. They are also solid unit dosage forms, which disintegrate in the mouth within a minute in the presence of saliva due to super disintegrants in the formulation. Thus this type of drug delivery helps a proper peroral administration in pediatric and geriatric population where swallowing is a matter of trouble. Various scientists have prepared orodispersible tablets by following various methods. However, the most common method of preparation is the compression method. Other special methods are molding, melt granulation, phase-transition process, sublimation, freeze-drying, spray-drying, and effervescent method. Since these tablets dissolve directly in the mouth, so, their taste is also an important factor. Various approaches have been taken in order to mask the bitter taste of the drug. A number of scientists have explored several drugs in this field. Like all other solid dosage forms, they are also evaluated in the field of hardness, friability, wetting time, moisture uptake, disintegration test, and dissolution test. PMID:22096326

Extraction of extracellular polymeric substances from aerobic granule with compact interior structure.

PubMed

Adav, Sunil S; Lee, Duu-Jong

2008-06-15

Extracellular polymeric substances (EPS) were extracted from aerobic granules of compact interior structure using seven extraction methods. Ultrasound followed by the chemical reagents formamide and NaOH outperformed other methods in extracting EPS from aerobic granules of compact interior. The collected EPS revealed no contamination by intracellular substances and consisted mainly of proteins, polysaccharides, humic substances and lipids. The quantity of extracted proteins exhibited a weak correlation with quantity of extracted carbohydrates but no correlation with quantity of extracted humic substances. The total polysaccharides/total proteins (PN/PS) ratios for sludge flocs were approximately 0.9 regardless of extraction method. Protein content was significantly enriched in the granules, producing a PN/PS ratio of 3.4-6.2. This experimental result correlated with observations using excitation-emission matrix (EEM) and confocal laser scanning microscope technique. However, detailed study disproved the use of EEM results as a quantitative index of extracted EPS from sludge flocs or from granules.

A Method for Extracting Pigments from Squid Doryteuthis pealeii.

PubMed

DiBona, Christopher W; Williams, Thomas L; Dinneen, Sean R; Jones Labadie, Stephanie F; Deravi, Leila F

2016-11-09

Cephalopods can undergo rapid and adaptive changes in dermal coloration for sensing, communication, defense, and reproduction purposes. These capabilities are supported in part by the areal expansion and retraction of pigmented organs known as chromatophores. While it is known that the chromatophores contain a tethered network of pigmented granules, their structure-function properties have not been fully detailed. We describe a method for isolating the nanostructured granules in squid Doryteuthis pealeii chromatophores and demonstrate how their associated pigments can be extracted in acidic solvents. To accomplish this, the chromatophore containing dermal layer is first manually isolated using a superficial dissection, and the pigment granules are removed using sonication, centrifugation, and washing cycles. Pigments confined within the purified granules are then extracted via acidic methanol solutions, leaving nanostructures with smaller diameters that are void of visible color. This extraction procedure produces a 58% yield of soluble pigments isolated from granules. Using this method, the composition of the chromatophore pigments can be determined and used to provide insight into the mechanism of adaptive coloration in cephalopods.

Novel Approach to Strengthening Ceramic Cathode Contact and Validation in a Generic Stack Test Fixture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, Yeong-Shyung; Bonnett, Jeff F.; Stevenson, Jeffry W.

The ceramic contact material at the cathode side has been identified as the weakest mechanical link in solid oxide fuel cells, due to poor sintering at low stack fabrication temperatures. In this work, a novel approach of mechanical interlocking with an engineered surface was proposed to strengthen LSM-type contacts. The engineered cathode surface was made by depositing large LSM20 granules onto a wet cathode print, followed by sintering. Granules of three sizes were tested (mesh #35, #60, and #100). Small coupons of anode-supported YSZ electrolyte with LSM cathode were joined at 850 and 950oC for 2h with LSM contact usingmore » either the engineered surface or plain surfaces. The results of contact strength measurements showed about 14 times increase with engineered surface compared to plain surfaces. Validation with a 2”x2” LSM-based cell in a generic stack fixture showed good thermal cycle stability with minimal change in ohmic impedance over ten cycles.« less

Structural design approaches for creating fat droplet and starch granule mimetics.

PubMed

McClements, David Julian; Chung, Cheryl; Wu, Bi-Cheng

2017-02-22

This article focuses on hydrogel-based strategies for creating reduced calorie foods with desirable physicochemical, sensory, and nutritional properties. Initially, the role of fat droplets and starch granules in foods is discussed, and then different methods for fabricating hydrogel beads are reviewed, including phase separation, antisolvent precipitation, injection, and emulsion template methods. Finally, the potential application of hydrogel beads as fat droplet and starch granule replacements is discussed. There is still a need for large-scale, high-throughout, and economical methods of fabricating hydrogel beads suitable for utilization within the food industry.

Aerobic granules formation and nutrients removal characteristics in sequencing batch airlift reactor (SBAR) at low temperature.

PubMed

Bao, Ruiling; Yu, Shuili; Shi, Wenxin; Zhang, Xuedong; Wang, Yulan

2009-09-15

To understand the effect of low temperature on the formation of aerobic granules and their nutrient removal characteristics, an aerobic granular sequencing batch airlift reactor (SBAR) has been operated at 10 degrees C using a mixed carbon source of glucose and sodium acetate. The results showed that aerobic granules were obtained and that the reactor performed in stable manner under the applied conditions. The granules had a compact structure and a clear out-surface. The average parameters of the granules were: diameter 3.4mm, wet density 1.036 g mL(-1), sludge volume index 37 mL g(-1), and settling velocity 18.6-65.1 cm min(-1). Nitrite accumulation was observed, with a nitrite accumulation rate (NO(2)(-)-N/NO(x)(-)-N) between 35% and 43% at the beginning of the start-up stage. During the stable stage, NO(x) was present at a level below the detection limit. However, when the influent COD concentration was halved (resulting in COD/N a reduction of the COD/N from 20:1 to 10:1) nitrite accumulation was observed once more with an effluent nitrite accumulation rate of 94.8%. Phosphorus release was observed in the static feeding phase and also during the initial 20-30 min of the aerobic phase. Neither the low temperature nor adjustment of the COD/P ratio from 100:1 to 25:1 had any influence on the phosphorus removal efficiency under the operating conditions. In the granular reactor with the influent load rates for COD, NH(4)(+)-N, and PO(4)(3-)-P of 1.2-2.4, 0.112 and 0.012-0.024 kg m(-3)d(-1), the respective removal efficiencies at low temperature were 90.6-95.4%, 72.8-82.1% and 95.8-97.9%.

Novel insights into RNP granules by employing the trypanosome's microtubule skeleton as a molecular sieve.

PubMed

Fritz, Melanie; Vanselow, Jens; Sauer, Nadja; Lamer, Stephanie; Goos, Carina; Siegel, T Nicolai; Subota, Ines; Schlosser, Andreas; Carrington, Mark; Kramer, Susanne

2015-09-18

RNP granules are ribonucleoprotein assemblies that regulate the post-transcriptional fate of mRNAs in all eukaryotes. Their exact function remains poorly understood, one reason for this is that RNP granule purification has not yet been achieved. We have exploited a unique feature of trypanosomes to prepare a cellular fraction highly enriched in starvation stress granules. First, granules remain trapped within the cage-like, subpellicular microtubule array of the trypanosome cytoskeleton while soluble proteins are washed away. Second, the microtubules are depolymerized and the granules are released. RNA sequencing combined with single molecule mRNA FISH identified the short and highly abundant mRNAs encoding ribosomal mRNAs as being excluded from granules. By mass spectrometry we have identified 463 stress granule candidate proteins. For 17/49 proteins tested by eYFP tagging we have confirmed the localization to granules, including one phosphatase, one methyltransferase and two proteins with a function in trypanosome life-cycle regulation. The novel method presented here enables the unbiased identification of novel RNP granule components, paving the way towards an understanding of RNP granule function. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Application of image processing on struvite recovery from swine wastewater by using the fluidized bed.

PubMed

Ye, Zhi-Long; Deng, Yujun; Ye, Xin; Lou, Yaoyin; Chen, Shaohua

2018-01-01

Fluidized granulation is one of the common methods used in wastewater treatment and resource recovery with harvesting millimeter-scale large particles. Presently, effective methods are lacking to measure the fluidized granules ranging from micro- to millimeter scales, with the consequence of ineffectively controlling and optimizing the granulation process. In this work, recovering struvite (MgNH 4 PO 4 ·6H 2 O) from swine wastewater by using a fluidized bed was taken as an example. Image processing was applied to analyze the properties of different types of struvite granules, including morphology, particle size distribution, number density and mass concentration. Four stages of the struvite crystal evolution were therefore defined: aggregation, aggregate compaction, cluster-agglomerating and coating growth. These stages could occur simultaneously or sequentially. Up-flow rates of 30-80 mm/s in the fluidized bed sustained 600-876 g/L granular solids. Results revealed that the coating-growth granules were formed with compact aggregates or cluster-agglomerating granules as the nuclei. The growth rates for the different types of particles, including population growth, mass increase and particle size enlargement, were determined. In final, a schematic illustration for struvite granulation process is also presented.

Evaluation of the physicochemical properties and compaction behavior of melt granules produced in microwave-induced and conventional melt granulation in a single pot high shear processor.

PubMed

Loh, Z H; Sia, B Y; Heng, Paul W S; Lee, C C; Liew, Celine V

2011-12-01

Recently, microwave-induced melt granulation was shown to be a promising alternative to conventional melt granulation with improved process monitoring capabilities. This study aimed to compare the physicochemical and compaction properties of granules produced from microwave-induced and conventional melt granulation. Powder admixtures comprising equivalent proportions by weight of lactose 200 M and anhydrous dicalcium phosphate were granulated with polyethylene glycol 3350 under the influence of microwave-induced and conventional heating in a 10-L single pot high shear processor. The properties of the granules and compacts produced from the two processes were compared. Relative to conventional melt granulation, the rates at which the irradiated powders heated up in microwave-induced melt granulation were lower. Agglomerate growth proceeded at a slower rate, and this necessitated longer massing durations for growth induction. These factors prompted greater evaporative moisture losses from the melt granules. Additionally, nonuniform heating of the powders under the influence of microwaves led to increased inter-batch variations in the binder contents of resultant melt granules and a reliance of content homogeneity on massing duration. Agglomerate growth proceeded more rapidly under the influence of conventional heating due to the enhanced heating capabilities of the powders. Melt granules produced using the conventional method possessed higher moisture contents and improved content homogeneity. The compaction behavior of melt granules were affected by their mean sizes, porosities, flow properties, binder, and moisture contents. The last two factors were responsible for the disparities in compaction behavior of melt granules produced from microwave-induced and conventional melt granulation.

Metal hydride composition and method of making

DOEpatents

Congdon, James W.

1995-01-01

A dimensionally stable hydride composition and a method for making such a composition. The composition is made by forming particles of a metal hydride into porous granules, mixing the granules with a matrix material, forming the mixture into pellets, and sintering the pellets in the absence of oxygen. The ratio of matrix material to hydride is preferably between approximately 2:1 and 4:1 by volume. The porous structure of the granules accommodates the expansion that occurs when the metal hydride particles absorb hydrogen. The porous matrix allows the flow of hydrogen therethrough to contact the hydride particles, yet supports the granules and contains the hydride fines that result from repeated absorption/desorption cycles.

Antimicrobial-Coated Granules for Disinfecting Water

NASA Technical Reports Server (NTRS)

Akse, James R.; Holtsnider, John T.; Kliestik, Helen

2011-01-01

Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

HPLC-DAD-ELSD Combined Pharmacodynamics and Serum Medicinal Chemistry for Quality Assessment of Huangqi Granule

PubMed Central

Zhao, Yang; Gong, Xiao-Jian; He, Yan; Ma, Feng-Wei; Zhou, Mei; Zhao, Chao; Niu, Yi; Deng, Jie

2015-01-01

Objective To more scientifically and reasonably control the quality of Huangqi Granules, preliminary studies on the pharmacodynamics and serum pharmacochemistry of this medicine were performed. DPPH and MTT experiments showed that water extracts of Huangqi Granules had good antioxidant activity and increased immunity. Timed blood samples collected 5 min, 15 min, and 30 min after oral administration of a set amount of Huangqi Granules were collected and tested using UPLC-ESI-MS/MS. As a result, calycosin-7-O-β-D-glucoside, ononin, calycosin, astragaloside IV, and formononetin were found to exist in rat blood after dosing, indicating that the five chemical compounds might have pharmacological activity, and based on this result, they were designated biomarkers for quality control of Huangqi Granules. Consequently, a simple, rapid and efficient method was developed in the present study for the simultaneous determination of the five characteristic compounds in Huangqi Granules using HPLC-DAD-ELSD. Materials and Methods The separation was performed using an Agilent Hypersil ODS column (4.6 × 250 mm, 5 μm) at 30 ℃. The mobile phase was composed of water (solvent A) and acetonitrile (solvent B) with a flow rate of 1 mL/min. The drift tube temperature of the ELSD system was set to 85 ℃, and the nitrogen pressure was 3.5 bar. Results All five characteristic compounds had good linear behavior with r2 values greater than 0.9972. The recoveries varied from 96.31% to 101.22%. Subsequently, the developed method was applied to evaluate the quality of Huangqi Granules from different batches, and hierarchical clustering analysis (HCA) was used to analyze the classification of the samples based on the values of the five compounds. Conclusion The established HPLC method combined with HCA proved to be effective to evaluate the quality of Huangqi Granules. PMID:25915040

Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

PubMed

Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

2009-02-01

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

Simultaneous Comparison of Two Roller Compaction Techniques and Two Particle Size Analysis Methods.

PubMed

Saarinen, Tuomas; Antikainen, Osmo; Yliruusi, Jouko

2017-11-01

A new dry granulation technique, gas-assisted roller compaction (GARC), was compared with conventional roller compaction (CRC) by manufacturing 34 granulation batches. The process variables studied were roll pressure, roll speed, and sieve size of the conical mill. The main quality attributes measured were granule size and flow characteristics. Within granulations also the real applicability of two particle size analysis techniques, sieve analysis (SA) and fast imaging technique (Flashsizer, FS), was tested. All granules obtained were acceptable. In general, the particle size of GARC granules was slightly larger than that of CRC granules. In addition, the GARC granules had better flowability. For example, the tablet weight variation of GARC granules was close to 2%, indicating good flowing and packing characteristics. The comparison of the two particle size analysis techniques showed that SA was more accurate in determining wide and bimodal size distributions while FS showed narrower and mono-modal distributions. However, both techniques gave good estimates for mean granule sizes. Overall, SA was a time-consuming but accurate technique that provided reliable information for the entire granule size distribution. By contrast, FS oversimplified the shape of the size distribution, but nevertheless yielded acceptable estimates for mean particle size. In general, FS was two to three orders of magnitude faster than SA.

Maltodextrin: a novel excipient used in sugar-based orally disintegrating tablets and phase transition process.

PubMed

Elnaggar, Yosra Shaaban R; El-Massik, Magda A; Abdallah, Ossama Y; Ebian, Abd Elazim R

2010-06-01

The recent challenge in orally disintegrating tablets (ODT) manufacturing encompasses the compromise between instantaneous disintegration, sufficient hardness, and standard processing equipment. The current investigation constitutes one attempt to fulfill this challenge. Maltodextrin, in the present work, was utilized as a novel excipient to prepare ODT of meclizine. Tablets were prepared by both direct compression and wet granulation techniques. The effect of maltodextrin concentrations on ODT characteristics--manifested as hardness and disintegration time--was studied. The effect of conditioning (40 degrees C and 75% relative humidity) as a post-compression treatment on ODT characteristics was also assessed. Furthermore, maltodextrin-pronounced hardening effect was investigated using differential scanning calorimetry (DSC) and X-ray analysis. Results revealed that in both techniques, rapid disintegration (30-40 s) would be achieved on the cost of tablet hardness (about 1 kg). Post-compression conditioning of tablets resulted in an increase in hardness (3 kg), while keeping rapid disintegration (30-40 s) according to guidance of the FDA for ODT. However, direct compression-conditioning technique exhibited drawbacks of long conditioning time and appearance of the so-called patch effect. These problems were, yet, absent in wet granulation-conditioning technique. DSC and X-ray analysis suggested involvement of glass-elastic deformation in maltodextrin hardening effect. High-performance liquid chromatography analysis of meclizine ODT suggested no degradation of the drug by the applied conditions of temperature and humidity. Overall results proposed that maltodextrin is a promising saccharide for production of ODT with accepted hardness-disintegration time compromise, utilizing standard processing equipment and phenomena of phase transition.

Specific lignin accumulation in granulated juice sacs of Citrus maxima.

PubMed

Wu, Jia-Ling; Pan, Teng-Fei; Guo, Zhi-Xiong; Pan, Dong-Ming

2014-12-17

Juice sac granulation occurring in pummelo fruits [Citrus maxima (Burm.) Merr.] is an undesirable trait, and the underlying mechanism remains unresolved. Previous studies have shown that lignin metabolism is closely associated with the process of juice sac granulation. Here, a method suitable for lignin isolation from pummelo tissues is established. Acetylated lignins from different pummelo tissues and cultivars were analyzed by HSQC NMR. The results showed that lignins in granulated juice sacs were characterized by an extremely high abundance of guaiacyl units (91.13-96.82%), in contrast to lignins from other tissues, including leaves, stems, and segment membranes. The abnormally accumulated lignins in granulated juice sacs were specific and mainly polymerized from coniferyl alcohol. No significant difference was found in lignin types among various cultivars. These findings indicated that the mechanism of juice sac granulation might be similar among various cultivars, although very different degrees of juice sac granulation can be observed.

Bioequivalence among three methods of administering pantoprazole granules in healthy subjects.

PubMed

Tammara, Brinda; Weisel, Kathy; Katz, Arie; Meng, Xu

2009-11-01

The bioequivalence among three methods of administering pantoprazole granules was studied in healthy subjects. In this randomized, open-label, three-period, crossover study, 25 healthy adults received a single 40-mg dose of pantoprazole granules with applesauce orally, with apple juice orally, and with apple juice administered via a nasogastric tube. Subjects were randomly assigned to one of six treatment sequences. Blood samples were collected within 2 hours before treatment administration on study day 1 and at 0.33, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 16, and 24 hours after treatment administration. Plasma pantoprazole concentrations were analyzed by a validated liquid chromatography-tandem mass spectrometry method. The plasma pantoprazole concentration-time data for each subject were analyzed using noncompartmental methods. The 90% confidence intervals (CIs) for the test:reference geometric mean ratio were calculated for the peak pantoprazole concentration (C(max) ) and area under the concentration-time curve (AUC). Of the 25 subjects enrolled, 100% completed the study. The mean C(max) and AUC values were similar for the three administration methods. The 90% CIs for the ratios of the geometric means of the granules in apple juice orally (92.4-112.5%) and in apple juice administered through a nasogastric tube (102.7-125.2%), relative to the granules administered with applesauce orally, were essentially within the bioequivalent limits of 80-125%. No serious adverse events or study discontinuations occurred. Three methods of administering pantoprazole delayed-release granules for oral suspension-with apple juice orally, with applesauce orally, and with apple juice through a nasogastric tube--were bioequivalent in healthy subjects.

Metal hydride composition and method of making

DOE Office of Scientific and Technical Information (OSTI.GOV)

Congdon, J.W.

1995-08-22

A dimensionally stable hydride composition and a method for making such a composition are disclosed. The composition is made by forming particles of a metal hydride into porous granules, mixing the granules with a matrix material, forming the mixture into pellets, and sintering the pellets in the absence of oxygen. The ratio of matrix material to hydride is preferably between approximately 2:1 and 4:1 by volume. The porous structure of the granules accommodates the expansion that occurs when the metal hydride particles absorb hydrogen. The porous matrix allows the flow of hydrogen there through to contact the hydride particles, yetmore » supports the granules and contains the hydride fines that result from repeated absorption/desorption cycles. 3 figs.« less

Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

PubMed

Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-04-25

Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

Quantitative Determination of Fluorine Content in Blends of Polylactide (PLA)–Talc Using Near Infrared Spectroscopy

PubMed Central

Tamburini, Elena; Tagliati, Chiara; Bonato, Tiziano; Costa, Stefania; Scapoli, Chiara; Pedrini, Paola

2016-01-01

Near-infrared spectroscopy (NIRS) has been widely used for quantitative and/or qualitative determination of a wide range of matrices. The objective of this study was to develop a NIRS method for the quantitative determination of fluorine content in polylactide (PLA)-talc blends. A blending profile was obtained by mixing different amounts of PLA granules and talc powder. The calibration model was built correlating wet chemical data (alkali digestion method) and NIR spectra. Using FT (Fourier Transform)-NIR technique, a Partial Least Squares (PLS) regression model was set-up, in a concentration interval of 0 ppm of pure PLA to 800 ppm of pure talc. Fluorine content prediction (R2cal = 0.9498; standard error of calibration, SEC = 34.77; standard error of cross-validation, SECV = 46.94) was then externally validated by means of a further 15 independent samples (R2EX.V = 0.8955; root mean standard error of prediction, RMSEP = 61.08). A positive relationship between an inorganic component as fluorine and NIR signal has been evidenced, and used to obtain quantitative analytical information from the spectra. PMID:27490548

Fluidized-Bed Drying and Storage Stability of Cryptococcus flavescens OH 182.9, a Biocontrol Agent of Fusarium Head Blight

USDA-ARS?s Scientific Manuscript database

A method to produce dried granules of Cryptococcus flavescens (formerly Cryptococcus nodaensis) OH 182.9 was developed and the granules evaluated for storage stability. Small spherical granules were produced and dried using a fluidized bed dryer. A drying and survival curve was produced for the pr...

[A method for the primary culture of fibroblasts isolated from human airway granulation tissues].

PubMed

Chen, Nan; Zhang, Jie; Xu, Min; Wang, Yu-ling; Pei, Ying-hua

2013-04-01

To establish a feasible method to culture primary fibroblasts isolated from human airway granulation tissues, and therefore to provide experimental data for the investigation of the pathogenesis of benign airway stenosis. The granulation tissues were collected from 6 patients during routine bronchoscopy at our department of Beijing Tiantan Hospital from April to June 2011. Primary fibroblasts were obtained by culturing the explanted tissues. Cell growth was observed under inverted microscope. All of these 6 primary cultures were successful. Fibroblast-like cells were observed to migrate from the tissue pieces 3 d after inoculation. After 9-11 d of culture, cells reached to 90% confluence and could be sub-cultured. After passage, the cells were still in a typical elongated spindle-shape and grew well. The cells could be sub-cultured further when they formed a monolayer. Explant culture is a reliable method for culturing primary fibroblasts from human airway granulation tissues.

In-line monitoring of granule moisture in fluidized-bed dryers using microwave resonance technology.

PubMed

Buschmüller, Caroline; Wiedey, Wolfgang; Döscher, Claas; Dressler, Jochen; Breitkreutz, Jörg

2008-05-01

This is the first report on in-line moisture measurement of pharmaceutical products by microwave resonance technology. In order to meet the FDA's PAT approach, a microwave resonance sensor appropriate for pharmaceutical use was developed and implemented into two different fluidized-bed dryers. The novel sensor enables a continuous moisture measurement independent from the product density. Hence, for the first time precise real time determination of the moisture in pharmaceutical granules becomes possible. The qualification of the newly developed sensor was performed by drying placebo granules under experimental conditions and the validation using drug loaded granules under real process conditions. The results of the investigations show good correlations between water content of the granules determined by the microwave resonance sensor and both reference methods, loss on drying by infrared light exposure and Karl Fischer titration. Furthermore, a considerable time saving in the drying process was achieved through monitoring the residual water content continuously by microwave resonance technology instead of the formerly used discontinuous methods.

High-rate hydrogenotrophic methanogenesis for biogas upgrading: the role of anaerobic granules.

PubMed

Xu, Heng; Gong, Shufen; Sun, Yuanzi; Ma, Hailing; Zheng, Mingyue; Wang, Kaijun

2015-01-01

Hydrogenotrophic methanogenesis has been proved to be a feasible biological method for biogas upgrading. To improve its performance, the feasibility of typical anaerobic granules as the inoculum was investigated in both batch and continuous experiments. The results from batch experiments showed that glucose-acclimated granules seemed to perform better than granules acclimated to acidified products (AP, i.e. acetate, propionate and ethanol) in in situ biogas upgrading systems and a slightly higher H2 consumption rate (1.5 mmol H2 g VSS(-1) h(-1)) was obtained for glucose-acclimated granules. For AP-acclimated granules, the inhibition on anaerobic digestion and pH increase (up to 9.55±0.16) took place, and the upgrading performance was adversely affected. In contrast, better performance for AP-acclimated granules was observed in ex situ systems, possibly due to their higher hydrogenotrophic methanogenic activities (HMA). Moreover, when gas-liquid mass transfer limitations were alleviated, the upgrading performance was significantly improved (three-fold) for both glucose-acclimated and AP-acclimated granules. The HMA of anaerobic granules could be further enhanced to improve biogas upgrading performance via continuous cultivation with H2/CO2 as the sole substrate. During the three months' cultivation, secondary granulation and microbial population shift were observed, but anaerobic granules still remained intact and their HMA increased from 0.2 to 0.6 g COD g VSS(-1) d(-1). It indicated that the formation of hydrogenotrophic methanogenic granules, a new type of anaerobic granules specialized for high-rate hydrogenotrophic methanogenesis and biogas upgrading, might be possible. Conclusively, anaerobic granules showed great potential for biogas upgrading.

Tracheal Wall Thickening Is Associated with the Granulation Tissue Formation Around Silicone Stents in Patients with Post-Tuberculosis Tracheal Stenosis

PubMed Central

Eom, Jung Seop; Jeon, Kyeongman; Um, Sang-Won; Koh, Won-Jung; Suh, Gee Young; Chung, Man Pyo; Kwon, O Jung

2013-01-01

Purpose Tracheal restenosis due to excessive granulation tissue around a silicone stent requires repeated bronchoscopic interventions in patients with post-tuberculosis tracheal stenosis (PTTS). The current study was conducted to identify the risk factors for granulation tissue formation after silicone stenting in PTTS patients. Materials and Methods A retrospective study was conducted between January 1998 and December 2010. Forty-two PTTS patients with silicone stenting were selected. Clinical and radiological variables were retrospectively collected and analyzed. Results Tracheal restenosis due to granulation tissue formation were found in 20 patients (47.6%), and repeated bronchoscopic interventions were conducted. In multivariate analysis, tracheal wall thickness, measured on axial computed tomography scan, was independently associated with granulation tissue formation after silicone stenting. Furthermore, the degree of tracheal wall thickness was well correlated with the degree of granulation tissue formation. Conclusion Tracheal wall thickening was associated with granulation tissue formation around silicone stents in patients with post-tuberculosis tracheal stenosis. PMID:23709431

Gastroretentive extended-release floating granules prepared using a novel fluidized hot melt granulation (FHMG) technique.

PubMed

Zhai, H; Jones, D S; McCoy, C P; Madi, A M; Tian, Y; Andrews, G P

2014-10-06

The objective of this work was to investigate the feasibility of using a novel granulation technique, namely, fluidized hot melt granulation (FHMG), to prepare gastroretentive extended-release floating granules. In this study we have utilized FHMG, a solvent free process in which granulation is achieved with the aid of low melting point materials, using Compritol 888 ATO and Gelucire 50/13 as meltable binders, in place of conventional liquid binders. The physicochemical properties, morphology, floating properties, and drug release of the manufactured granules were investigated. Granules prepared by this method were spherical in shape and showed good flowability. The floating granules exhibited sustained release exceeding 10 h. Granule buoyancy (floating time and strength) and drug release properties were significantly influenced by formulation variables such as excipient type and concentration, and the physical characteristics (particle size, hydrophilicity) of the excipients. Drug release rate was increased by increasing the concentration of hydroxypropyl cellulose (HPC) and Gelucire 50/13, or by decreasing the particle size of HPC. Floating strength was improved through the incorporation of sodium bicarbonate and citric acid. Furthermore, floating strength was influenced by the concentration of HPC within the formulation. Granules prepared in this way show good physical characteristics, floating ability, and drug release properties when placed in simulated gastric fluid. Moreover, the drug release and floating properties can be controlled by modification of the ratio or physical characteristics of the excipients used in the formulation.

Characterization and evaluation of avermectin solid nanodispersion prepared by microprecipitation and lyophilisation techniques

PubMed Central

Wang, Chunxin; Zhao, Xiang; Yao, Junwei; Zeng, Zhanghua; Wang, Yan; Sun, Changjiao; Liu, Guoqiang; Cui, Haixin

2018-01-01

Poorly water-soluble and photosensitive pesticide compounds are difficult to formulate as solvent-free nanoformulations with high efficacy. A avermectin solid nanodispersion with a mean particle size of 188 nm was developed by microprecipitation and lyophilisation techniques. The suspensibility and wetting time of the solid nanodispersion in water were 99.8% and 13 s, respectively, superior to those of conventional water dispersible granules and wettable powders. The anti-photolysis performance of the nanoformulation was twice that of the technical material, and the biological activity against diamondback moths was more than 1.5 times that of the conventional solid formulations while taking LC 50 as the evaluation index. Moreover, the formulation composition substantially decreased the surfactant content and avoided organic solvents. Microprecipitation combined with lyophilisation is an easy and promising method to construct solid nanoformulations for pesticides with poor water solubility and environmental sensitivity. The application of the highly effective solid nanodispersion in crop production will have a great potential in reducing chemical residues and environmental pollution. PMID:29360866

Polysaccharides-based multiparticulated interpolyelectrolyte complexes for controlled benznidazole release.

PubMed

García, Mónica C; Manzo, Rubén H; Jimenez-Kairuz, Alvaro

2018-07-10

Polysaccharides-based delivery systems and interpolyelectrolyte complexes (IPECs) are interesting alternatives to control the release of drugs, thereby improving therapies. Benznidazole (BZ) is the selected drug for Chagas disease pharmacotherapy. However, its side effects limit its efficacy and safety. We developed novel multiparticulated BZ-loaded IPECs based on chitosan and alginic acid, and investigated their physicochemical and pharmacotechnical properties. IPECs were obtained using the casting solvent method, followed by wet granulation. They presented ionic interaction between the biopolymers, revealed that free BZ was uniformly distributed and showed adequate flow properties for hard gelatin-capsule formulation. The multiparticles exhibited mucoadhesion properties and revealed modulation of BZ release, depending on the release media, in accordance with the fluid uptake. The IPECs developed possess interesting properties that are promising for the design of novel alternatives to improve Chagas disease pharmacotherapy, which would diminish BZ's adverse effects and/or allow a reduction in the frequency of BZ administration. Copyright © 2018 Elsevier B.V. All rights reserved.

Low level drug product API form analysis - Avalide tablet NIR quantitative method development and robustness challenges.

PubMed

Pan, Duohai; Crull, George; Yin, Shawn; Grosso, John

2014-02-01

Avalide(@), a medication used for the treatment of hypertension, is a combination of Irbesartan, and Hydrochlorothiazide. Irbesartan, one of the active pharmaceutical ingredients (API) in Avalide products, exists in two neat crystalline forms: Form A and Form B. Irbesartan Form A is the API form used in a wet granulation for the preparation of Avalide tablets. The presence of the less soluble Irbesartan Form B in Avalide tablets may result in the slower dissolution. In this paper, we have presented our work on the method development, verification and challenges of quantitatively detecting, via NIR and ssNMR, very small amounts of Irbesartan Form B in Avalide tablets. As part of the NIR method development and qualification, limit of detection, linearity and accuracy were examined. In addition, a limited study of the robustness of the method was conducted and a bias in the level of Form B was correlated to the ambient humidity. ssNMR, a primary method for the determination of polymorphic composition, was successfully used as an orthogonal technique to verify the accuracy of the NIR method and added to the confidence in the NIR method. The speed and efficiency of the NIR method make it a suitable and convenient tool for routine analysis of Avalide tablets for Form B in a QC environment. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of in line monitored fluid bed granulation process parameters on the stability of Ethinylestradiol.

PubMed

Roßteuscher-Carl, Katrin; Fricke, Sabine; Hacker, Michael C; Schulz-Siegmund, Michaela

2015-12-30

Ethinylestradiol (EE) as a highly active and low dosed compound is prone to oxidative degradation. The stability of the drug substance is therefore a critical parameter that has to be considered during drug formulation. Beside the stability of the drug substance, granule particle size and moisture are critical quality attributes (CQA) of the fluid bed granulation process which influence the tableting ability of the resulting granules. Both CQA should therefore be monitored during the production process by process analytic technology (PAT) according to ICH Q8. This work focusses on the effects of drying conditions on the stability of EE in a fluid-bed granulation process. We quantified EE degradation products 6-alpha-hydroxy-EE, 6-beta-hydroxy-EE, 9(11)-dehydro-EE and 6-oxo-EE during long time storage and accelerated conditions. PAT-tools that monitor granule particle size (Spatial filtering technology) and granule moisture (Microwave resonance technology) were applied and compared with off-line methods. We found a relevant influence of residual granule moisture and thermic stress applied during granulation on the storage stability of EE, whereas no degradation was found immediately after processing. Hence we conclude that drying parameters have a relevant influence on long term EE stability. Copyright © 2015 Elsevier B.V. All rights reserved.

Comparative study on fluorescence spectra of Chinese medicine north and south isatis root granules

NASA Astrophysics Data System (ADS)

Liang, Lan; He, Qing; Chen, Zhenqiang; Zhu, Siqi

2016-03-01

Since the spectral imaging technology emerged, it has gained a lot of application achievements in the military field, precision agriculture and biomedical science. When the fluorescence spectrum imaging first applied to the detection of the feature resource of Chinese herbal medicine, the characteristics of holistic and ambiguity made it a new approach to the traditional Chinese medicine testing. In this paper, we applied this method to study the Chinese medicine north and south isatis root granules by comparing their fluorescence spectra. Using cluster analysis, the results showed that the north and south Banlangen can not be divided by ascription. And these indicate that there is a large difference in the quality of Banlangen granules on the market, and fluorescence spectrum imaging method can be used in monitoring the quality of radix isatidis granules.

Gray-level co-occurrence matrix analysis of several cell types in mouse brain using resolution-enhanced photothermal microscopy

NASA Astrophysics Data System (ADS)

Kobayashi, Takayoshi; Sundaram, Durga; Nakata, Kazuaki; Tsurui, Hiromichi

2017-03-01

Qualifications of intracellular structure were performed for the first time using the gray-level co-occurrence matrix (GLCM) method for images of cells obtained by resolution-enhanced photothermal imaging. The GLCM method has been used to extract five parameters of texture features for five different types of cells in mouse brain; pyramidal neurons and glial cells in the basal nucleus (BGl), dentate gyrus granule cells, cerebellar Purkinje cells, and cerebellar granule cells. The parameters are correlation, contrast, angular second moment (ASM), inverse difference moment (IDM), and entropy for the images of cells of interest in a mouse brain. The parameters vary depending on the pixel distance taken in the analysis method. Based on the obtained results, we identified that the most suitable GLCM parameter is IDM for pyramidal neurons and BGI, granule cells in the dentate gyrus, Purkinje cells and granule cells in the cerebellum. It was also found that the ASM is the most appropriate for neurons in the basal nucleus.

New Insights into PhaM-PhaC-Mediated Localization of Polyhydroxybutyrate Granules in Ralstonia eutropha H16

PubMed Central

Bresan, Stephanie

2017-01-01

ABSTRACT The formation and localization of polyhydroxybutyrate (PHB) granules in Ralstonia eutropha are controlled by PhaM, which interacts both with the PHB synthase (PhaC) and with the bacterial nucleoid. Here, we studied the importance of proline and lysine residues of two C-terminal PAKKA motifs in PhaM for their importance in attaching PHB granules to DNA by in vitro and in vivo methods. Substitution of the lysine residues but not of the proline residues resulted in detachment of formed PHB granules from the nucleoid. Instead, formation of PHB granule clusters at polar regions of the rod-shaped cells and an unequal distribution of PHB granules to daughter cells were observed. The formation of PHB granules was studied by the expression of chromosomally anchored gene fusions of fluorescent proteins with PhaM and PhaC in different backgrounds. PhaM and PhaC fusions showed a distinct colocalization at formed PHB granules in the nucleoid region of the wild type. In a ΔphaC background, PhaM and the catalytically inactive PhaCC319A protein were not able to form fluorescent foci, indicating that correct positioning requires the formation of PHB. Furthermore, time-lapse experiments revealed that PhaC and PhaM proteins detach from formed PHB granules at later stages, resulting in a nonhomogeneous population of PHB granules. This could explain why growth of individual PHB granules stops under PHB-permissive conditions at a certain size. IMPORTANCE PHB granules are storage compounds for carbon and energy in many prokaryotes. Equal distribution of accumulated PHB granules during cell division is therefore important for optimal fitness of the daughter cells. In R. eutropha, PhaM is responsible for maximal activity of PHB synthase, for initiation of PHB granule formation at discrete regions in the cells, and for association of formed PHB granules with the nucleoid. Here we found that four lysine residues of C-terminal PhaM sequence motifs are essential for association of PHB granules with the nucleoid. Furthermore, we followed PHB granule formation by time-lapse microscopy and provide evidence for aging of PHB granules that is manifested by detachment of previously PHB granule-associated PhaM and PHB synthase. PMID:28389545

Improved intracellular PHA determinations with novel spectrophotometric quantification methodologies based on Sudan black dye.

PubMed

Porras, Mauricio A; Villar, Marcelo A; Cubitto, María A

2018-05-01

The presence of intracellular polyhydroxyalkanoates (PHAs) is usually studied using Sudan black dye solution (SB). In a previous work it was shown that the PHA could be directly quantified using the absorbance of SB fixed by PHA granules in wet cell samples. In the present paper, the optimum SB amount and the optimum conditions to be used for SB assays were determined following an experimental design by hybrid response surface methodology and desirability-function. In addition, a new methodology was developed in which it is shown that the amount of SB fixed by PHA granules can also be determined indirectly through the absorbance of the supernatant obtained from the stained cell samples. This alternative methodology allows a faster determination of the PHA content (involving 23 and 42 min for indirect and direct determinations, respectively), and can be undertaken by means of basic laboratory equipment and reagents. The correlation between PHA content in wet cell samples and the spectra of the SB stained supernatant was determined by means of multivariate and linear regression analysis. The best calibration adjustment (R 2  = 0.91, RSE: 1.56%), and the good PHA prediction obtained (RSE = 1.81%), shows that the proposed methodology constitutes a reasonably precise way for PHA content determination. Thus, this methodology could anticipate the probable results of the above mentioned direct PHA determination. Compared with the most used techniques described in the scientific literature, the combined implementation of these two methodologies seems to be one of the most economical and environmentally friendly, suitable for rapid monitoring of the intracellular PHA content. Copyright © 2018 Elsevier B.V. All rights reserved.

Assessment of intra-granular and extra-granular fracture in the development of tablet tensile strength.

PubMed

Mitra, Biplob; Hilden, Jon; Litster, James D

2018-05-24

When a tablet is compacted from deformable granules and then broken, the fracture plane may cleave granules in two (intra-granular fracture) or separate neighboring granules (extra-granular fracture). In this study, a novel method was developed to quantify the extent of intra- versus extra-granular fracture by compacting tablets from multi-colored ideal granules and evaluating fracture surfaces. The proportions of intra-granular and extra-granular fracture were quantified and modeled in light of a new metric, the deformation potential, Δ, reflecting the solid fraction increase as an initial granule bed is compressed into a final tablet. Results show that a measurable tablet strength is achieved at Δ > 0.18, but intra-granular fracture is not observed until Δ > 0.21. At very large Δ, tablets experience almost exclusively intra-granular fracture, yet the tablet tensile strength is considerably lower than that of a tablet compacted from raw powders versus pre-compacted granules. Thus, secondary compaction of granules appears to weaken the granule matrix, leading to reduced tablet tensile strength even in the presence of strong extra-granular bonding. Copyright © 2018. Published by Elsevier Inc.

Particle size distribution of wheat starch granules in relation to baking properties of frozen dough.

PubMed

Tao, Han; Wang, Pei; Wu, Fengfeng; Jin, Zhengyu; Xu, Xueming

2016-02-10

The impact of freezing on the wheat starches with different particle size was studied using a range of characterization methods including X-ray diffraction, differential scanning calorimetry, the Rapid Visco Analyser and a reconstitution dough system. Wheat starches were fractionated into A- and B-type granules, and then subjected to freezing/thawing treatment for 3 cycles. The freezing treatment did not cause apparent damage on A-type granular surface but induced cracked structure on B-type granules. It facilitated materials such as amylose, proteins, and lipids leaching from starch granule and an increase in gelatinization temperatures, melting enthalpy, and pasting viscosities. A smaller bread specific volume was obtained from freezing-treated B-granules while the crumb firmness significantly increased (p>0.05). No marked differences were observed in the counterparts of A-granules after freezing treatment. It seemed that the B-type granules were more sensitive to the freezing/thawing treatment, thus facilitating structural transformations from dough to bread. Results indicated that the deterioration in frozen bread quality derived from starch could be minimized by increasing the A-granules content. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of alpha-amylase reaction mechanisms on analysis of resistant-starch contents.

PubMed

Moore, Samuel A; Ai, Yongfeng; Chang, Fengdan; Jane, Jay-lin

2015-01-22

This study aimed to understand differences in the resistant starch (RS) contents of native and modified starches obtained using two standard methods of RS content analysis: AOAC Method 991.43 and 2002.02. The largest differences were observed in native potato starch, cross-linked wheat distarch phosphate, and high-amylose corn starch stearic-acid complex (RS5) between using AOAC Method 991.43 with Bacillus licheniformis α-amylase (BL) and AOAC Method 2002.02 with porcine pancreatic α-amylase (PPA). To determine possible reasons for these differences, we hydrolyzed raw-starch granules with BL and PPA with equal activity at pH 6.9 and 37°C for up to 84 h and observed the starch granules displayed distinct morphological differences after the hydrolysis. Starches hydrolyzed by BL showed erosion on the surface of the granules; those hydrolyzed by PPA showed pitting on granule surfaces. These results suggested that enzyme reaction mechanisms, including the sizes of the binding sites and the reaction patterns of the two enzymes, contributed to the differences in the RS contents obtained using different methods of RS analysis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Granulated colloidal silicon dioxide-based self-microemulsifying tablets, as a versatile approach in enhancement of solubility and therapeutic potential of anti-diabetic agent: formulation design and in vitro/in vivo evaluation.

PubMed

Pandey, Vikas; Gilhotra, Ritu M; Kohli, Seema

2017-06-01

The current research work was executed with an aim to explore and promote the potential of self-microemusifying drug delivery systems (SMEDDS) in the form of tablets, in order to enhance solubility and oral bioavailability of poorly aqueous soluble drug Repaglinide (RPG). RPG-loaded liquid SMEDDS were developed consisting Labrafil M 1944CS, Kolliphor EL and Propylene glycol, which were then characterized on various parameters. After characterization and optimization, liquid SMEDDS were converted into solid form by adsorbing on Aeroperl® 300 pharma and polyplasdone TM XL. Further, selection of suitable excipients was done and mixed with prepared solidified SMEDDS powder followed by the preparation of self-microemulsifying tablets (SMET's) wet granulation-compression method. SMET's were subjected to differential scanning calorimetry (DSC) and particle X-ray diffraction (RXRD) studies, results of which indicated transformation of crystalline structure of RPG because of dispersion of RPG at molecular level in liquid SMEDDS. This was further assured by micrographs obtained from scanning electron microscope. SMET's shown more than 85% (30 min) of in vitro drug release in contrast to conventional marketed tablets (13.2%) and pure RPG drug (3.2%). Results of in vivo studies furnished that SMET's had shown marked decrease in the blood glucose level and prolonged duration of action (up to 8 h) in comparison with conventional marketed tablets and pure RPG drug. In conclusion, SMET's serves as a promising tool for successful oral delivery of poorly aqueous soluble drug(s) such as RPG.

Impact of chitosan as a disintegrant on the bioavailability of furosemide tablets: in vitro evaluation and in vivo simulation of novel formulations.

PubMed

Rasool, Bazigha Kadhim Abdul; Fahmy, Sahar Abdelsattar; Galeel, Omar Waleed Abdul

2012-10-01

To determine the effect of chitosan, starch powder, polyvinylpyrrolidone (PVP), Avicel PH 101 powder, Avicel PH 102 granules as a function of different concentrations on the solubility, disintegration and hence dissolution of furosemide from immediate release tablet dosage forms. The tablets were prepared by the wet granulation method and evaluated for hardness, friability, disintegration and in vitro dissolution. Chitosan 7% w/w showed the fastest disintegration of furosemide tablets among the other disintegrants studied. This was attributed to its highest swelling properties and velocity constant of water uptake. The step of adding chitosan during tablet preparation had a great effect on the physical properties and dissolution profiles of the prepared tablets with external addition of chitosan showed best results compared to best results comparing to internal-external or internal addition. The most appropriate force of compression was 4ton/cm(2). The selected formula F15 containing 7% w/w chitosan was successful and showed a high significant (p<0.001) enhancement in disintegration and dissolution behaviors of furosemide tablets in comparison with the commercially available Furosemide ® tablets. These results were supported by the simulated data where F15 formula showed the highest plasma concentration C-max 1.89mcg/mL after 0.5 hr compared to C-max 1.05mcg/mL after 1hr for the reference. The present study demonstrated that chitosan is a very good candidate to be used as a tablet disintegrant and was able to enhance the dissolution of poorly absorbable drugs.

Technical note: A method for isolating glycogen granules from ruminal protozoa for further characterization.

PubMed

Hall, Mary Beth

2016-03-01

Evaluation of physical, chemical, and enzymatic hydrolysis characteristics of protozoal glycogen is best performed on a pure substrate to avoid interference from other cell components. A method for isolating protozoal glycogen granules without use of detergents or other potentially contaminating chemicals was developed. Rumen inoculum was incubated anerobically in vitro with glucose. Glycogen-laden protozoa produced in the fermentation, primarily isotrichids, were allowed to sediment in a separatory funnel and were dispensed. The protozoa were processed through repeated centrifugations and sonication to isolate glycogen granules largely free of feed and cellular debris. The final water-insoluble lyophilized product analyzed as 98.3% α-glucan with very rare starch granules and 1.9% protein. Observed losses of glycogen granules during the clean-up process indicate that this procedure should not be used for quantitative assessment of protozoal glycogen from fermentations. Further optimization of this procedure to enhance the amount of glycogen obtained per fermentation may be possible. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Development of a reservoir type prolonged release system with felodipine via simplex methodology

PubMed Central

IOVANOV, RAREŞ IULIU; TOMUŢĂ, IOAN; LEUCUŢA, SORIN EMILIAN

2016-01-01

Background and aims Felodipine is a dihydropyridine calcium antagonist that presents good characteristics to be formulated as prolonged release preparations. The aim of the study was the formulation and in vitro characterization of a reservoir type prolonged release system with felodipine, over a 12 hours period using the Simplex method. Methods The first step of the Simplex method was to study the influence of the granules coating method on the felodipine release. Furthermore the influence of the coating polymer type, the percent of the coating polymer and the percent of pore forming agent in the coating on the felodipine release were studied. Afterwards these two steps of the experimental design the percent of Surelease applied on the felodipine loaded granules and the percent of pore former in the polymeric coating formulation variables were studied. The in vitro dissolution of model drug was performed in phosphate buffer solution (pH 6.5) with 1% sodium lauryl sulfate. The released drug quantification was done using an HPLC method. The release kinetics of felodipine from the final granules was assessed using different mathematical models. Results A 12 hours release was achieved using granules with the size between 315–500 μm coated with 45% Surelease with different pore former ratios in the coating via the top-spray method. Conclusion We have prepared prolonged release coated granules with felodipine using a fluid bed system based on the Simplex method. The API from the studied final formulations was released over a 12 hours period and the release kinetics of the model drug substance from the optimized preparations fitted best the Higuchi and Peppas kinetic models. PMID:27004036

Feasibility of surveying pesticide coverage with airborne fluorometer

NASA Technical Reports Server (NTRS)

Stoertz, G. E.; Hemphill, W. R.

1970-01-01

Response of a Fraunhofer line discriminator (FLD) to varying distributions of granulated corncobs stained with varying concentrations of Rhodamine WT dye was tested on the ground and from an H-19 helicopter. The granules are used as a vehicle for airborne emplacement of poison to control fire ants in the eastern and southeastern United States. Test results showed that the granules are detectable by FLD but that the concentration must be too great to be practical with the present apparatus. Possible methods for enhancement of response may include: (1) increasing dye concentration; (2) incorporating with the poisoned granules a second material to carry the dye alone; (3) use of a more strongly fluorescent substance (at 5890 A); (4) modifying the time interval after dyeing, or modifying the method of dyeing; (5) modifying the FLD for greater efficiency, increased field of view or larger optics; or (6) experimenting with laser-stimulated fluorescence.

The Underlying Physics in Wetted Particle Collisions

NASA Astrophysics Data System (ADS)

Donahue, Carly; Hrenya, Christine; Davis, Robert

2008-11-01

Wetted granular particles are relevant in many industries including the pharmaceutical and chemical industries and has applications to granulation, filtration, coagulation, spray coating, drying and pneumatic transport. In our current focus, we investigate the dynamics of a three-body normal wetted particle collision. In order to conduct collisions we use an apparatus called a ``Stokes Cradle,'' similar to the Newton's Cradle (desktop toy) except that the target particles are covered with oil. Here, we are able to vary the oil thickness, oil viscosity, and material properties. With a three particle collision there are four possible outcomes: fully agglomerated (FA); Newton's Cradle (NC), the striker and the first target ball are agglomerated and the last target ball is separated; Reverse Newton's Cradle (RNC), the striker is separated and the two targets are agglomerated; and fully separated (FS). Varying the properties of the collisions, we have observed all four outcomes. We use elastohydrodynamics as a theoretical basis for modeling the system. We also have considered the glass transition of the oil as the pressure increases upon impact and the cavitation of the oil as the pressure drops below the vapor pressure upon rebound. A toy model has been developed where the collision is modeled as a series of two-body collisions. A qualitative agreement between the toy model and experiments gives insight into the underlying physics.

Evaluation of rate of swelling and erosion of verapamil (VRP) sustained-release matrix tablets.

PubMed

Khamanga, Sandile M; Walker, Roderick B

2006-01-01

Tablets manufactured in-house were compared to a marketed sustained-release product of verapamil to investigate the rate of hydration, erosion, and drug-release mechanism by measuring the wet and subsequent dry weights of the products. Swelling and erosion rates depended on the polymer and granulating fluid used, which ultimately pointed to their permeability characteristics. Erosion rate of the marketed product was highest, which suggests that the gel layer that formed around these tablets was weak as opposed to the robust and resistant layers of test products. Anomalous and near zero-order transport mechanisms were dominant in tests and commercial product, respectively.

Granulation tissue of chronic pressure ulcers as a predictive indicator of wound closure.

PubMed

Wyffels, Jennifer T; Edsberg, Laura E

2011-10-01

: To describe the temporal relationship between the quantity of granulation tissue in a chronic pressure ulcer (PrU) and its clinical outcome. : Study participants were seen on days 0, 1, 2, 3, 4, 7, 8, 9, 10, 11, 14, 21, 28, 35, and 42. On each visit, the wounds were digitally photographed with a 3-cm calibration target. Images were analyzed using VeV MD (version 1.1.14; VERG Inc, Winnipeg, Manitoba, Canada) and Adobe Photoshop CS3 Extended (version 10.0.1; Adobe Systems Inc, San Jose, California). Granulation tissue was selected from calibrated digital images by 1 of 2 methods: manual selection and automated selection. Granulation tissue area was expressed as a percentage of total wound area. : Academic research laboratory. : Thirty-one chronic PrUs were observed in 27 subjects. : Quantitative measure of granulation tissue area. : There was no relationship between the amount of granulation tissue expressed as a percentage of the total PrU area and wound outcome. : This study is the first to both quantitatively measure the amount of granulation tissue in a chronic PrU and attempt to correlate it to wound outcome. Although counterintuitive, the amount of granulation tissue was not predictive of outcome, and no temporal trends could be described.

Adaptive Granulation-Based Prediction for Energy System of Steel Industry.

PubMed

Wang, Tianyu; Han, Zhongyang; Zhao, Jun; Wang, Wei

2018-01-01

The flow variation tendency of byproduct gas plays a crucial role for energy scheduling in steel industry. An accurate prediction of its future trends will be significantly beneficial for the economic profits of steel enterprise. In this paper, a long-term prediction model for the energy system is proposed by providing an adaptive granulation-based method that considers the production semantics involved in the fluctuation tendency of the energy data, and partitions them into a series of information granules. To fully reflect the corresponding data characteristics of the formed unequal-length temporal granules, a 3-D feature space consisting of the timespan, the amplitude and the linetype is designed as linguistic descriptors. In particular, a collaborative-conditional fuzzy clustering method is proposed to granularize the tendency-based feature descriptors and specifically measure the amplitude variation of industrial data which plays a dominant role in the feature space. To quantify the performance of the proposed method, a series of real-world industrial data coming from the energy data center of a steel plant is employed to conduct the comparative experiments. The experimental results demonstrate that the proposed method successively satisfies the requirements of the practically viable prediction.

Measuring stellar granulation during planet transits

NASA Astrophysics Data System (ADS)

Chiavassa, A.; Caldas, A.; Selsis, F.; Leconte, J.; Von Paris, P.; Bordé, P.; Magic, Z.; Collet, R.; Asplund, M.

2017-01-01

Context. Stellar activity and convection-related surface structures might cause bias in planet detection and characterization that use these transits. Surface convection simulations help to quantify the granulation signal. Aims: We used realistic three-dimensional (3D) radiative hydrodynamical (RHD) simulations from the Stagger grid and synthetic images computed with the radiative transfer code Optim3D to model the transits of three prototype planets: a hot Jupiter, a hot Neptune, and a terrestrial planet. Methods: We computed intensity maps from RHD simulations of the Sun and a K-dwarf star at different wavelength bands from optical to far-infrared that cover the range of several ground- and space-based telescopes which observe exoplanet transits. We modeled the transit using synthetic stellar-disk images obtained with a spherical-tile imaging method and emulated the temporal variation of the granulation intensity generating random images covering a granulation time-series of 13.3 h. We measured the contribution of the stellar granulation on the light curves during the planet transit. Results: We identified two types of granulation noise that act simultaneously during the planet transit: (I) the intrinsic change in the granulation pattern with timescale (e.g., 10 min for solar-type stars assumed in this work) is smaller than the usual planet transit ( hours as in our prototype cases); and (II) the fact that the transiting planet occults isolated regions of the photosphere that differ in local surface brightness as a result of convective-related surface structures. First, we showed that our modeling approach returns granulation timescale fluctuations that are comparable with what has been observed for the Sun. Then, our statistical approach shows that the granulation pattern of solar and K-dwarf-type stars have a non-negligible effect of the light curve depth during the transit, and, consequentially on the determination of the planet transit parameters such as the planet radius (up to 0.90% and 0.47% for terrestrial and gaseous planets, respectively). We also showed that larger (or smaller) orbital inclination angles with respect to values corresponding to transit at the stellar center display a shallower transit depth and longer ingress and egress times, but also granulation fluctuations that are correlated to the center-to-limb variation: they increase (or decrease) the value of the inclination, which amplifies the fluctuations. The granulation noise appears to be correlated among the different wavelength ranges either in the visible or in the infrared regions. Conclusions: The prospects for planet detection and characterization with transiting methods are excellent with access to large amounts of data for stars. The granulation has to be considered as an intrinsic uncertainty (as a result of stellar variability) on the precise measurements of exoplanet transits of planets. The full characterization of the granulation is essential for determining the degree of uncertainty on the planet parameters. In this context, the use of 3D RHD simulations is important to measure the convection-related fluctuations. This can be achieved by performing precise and continuous observations of stellar photometry and radial velocity, as we explained with RHD simulations, before, after, and during the transit periods.

Prediction on sunspot activity based on fuzzy information granulation and support vector machine

NASA Astrophysics Data System (ADS)

Peng, Lingling; Yan, Haisheng; Yang, Zhigang

2018-04-01

In order to analyze the range of sunspots, a combined prediction method of forecasting the fluctuation range of sunspots based on fuzzy information granulation (FIG) and support vector machine (SVM) was put forward. Firstly, employing the FIG to granulate sample data and extract va)alid information of each window, namely the minimum value, the general average value and the maximum value of each window. Secondly, forecasting model is built respectively with SVM and then cross method is used to optimize these parameters. Finally, the fluctuation range of sunspots is forecasted with the optimized SVM model. Case study demonstrates that the model have high accuracy and can effectively predict the fluctuation of sunspots.

Investigating the Use of Polymeric Binders in Twin Screw Melt Granulation Process for Improving Compactibility of Drugs.

PubMed

Batra, Amol; Desai, Dipen; Serajuddin, Abu T M

2017-01-01

Traditionally, the melt granulation for pharmaceutical products was performed at low temperature (<90°C) with high-shear granulators using low-melting waxy binders, and tablets produced using such granules were not amenable to large-scale manufacturing. The situation has changed in recent years by the use of twin screw extruder where the processing temperature could be increased to as high as 180°C and polymers with high T g could be used as binders. In this study, different polymeric binders were screened for their suitability in improving compactibility of 2 drugs, metformin hydrochloride and acetaminophen, by twin screw melt granulation. Processing temperatures for the 2 drugs were set at 180°C and 130°C, respectively. Screw configuration, screw speed, and feed rate were optimized such that all polymeric binders used produced granules. Several hydroxypropyl cellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone, and methacrylate-based polymers, including Klucel ® EXF, Eudragit ® EPO, and Soluplus ® , demonstrated good tablet tensile strength (>2 MPa) when granules were produced using only 10% wt/wt polymer concentration. Certain polymers provided acceptable compactibility even at 5% wt/wt. Thus, twin screw melt granulation process may be used with different polymers at a wide range of temperature. Due to low excipient concentration, this granulation method is especially suitable for high-dose tablets. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

NEW METHODOLOGY FOR DEVELOPMENT OF ORODISPERSIBLE TABLETS USING HIGH-SHEAR GRANULATION PROCESS.

PubMed

Ali, Bahaa E; Al-Shedfat, Ramadan I; Fayed, Mohamed H; Alanazi, Fars K

2017-05-01

Development of orodispersible delivery system of high mechanical properties and low disintegration time is a big challenge. The aim of the current work was to assess and optimize the high shear granulation process as a new methodology for development of orodispersible tablets of high quality attributes using design of experiment approach. A two factor, three levels (32), full factorial design was carried out to investigate the main and interaction effects of independent variables, water amount (XI) and granulation time (X2) on the characteristics of granules and final product, tablet. The produced granules were analyzed for their granule size, density and flowability. Furthermore, the produced tablets were tested for: weight variation, breaking force/ crushing strength, friability, disintegration time and drug dissolution. Regression analysis results of multiple linear models showed a high correlation between the adjusted R-squared and predicted R-squared for all granules and tablets characteristics, the difference is less than 0.2. All dependent responses of granules and tablets were found to be impacted significantly (p < 0.05) by the two independent variables. However, water amount demonstrated the most dominant effect for all granules and tablet characteristics as shown by higher its coefficient estimate for all selected responses. Numerical optimization using desirability function was performed to optimize the variables under study to provide orodispersible system within the USP limit with respect of mechanical properties and disintegration time. It was found that the higher desirability (0.915) could be attained at the low level pf water (180 g) and short granulation time (1.65 min). Eventually, this study provides the formulator with helpful information in selecting the proper level of water and granulation time to provide an orodispersible system of high crushing strength and very low disintegration time, when high shear granulation methodology was used as a method of manufacture.

Study of the scale-up, formulation, ageing and ammonia adsorption capacity of MIL-100(Fe), Cu-BTC and CPO-27(Ni) for use in respiratory protection filters.

PubMed

Hindocha, S; Poulston, S

2017-09-01

The metal-organic frameworks (MOFs) MIL-100(Fe), Cu-BTC and CPO-27(Ni) were synthesised in 1 kg batches. The materials were then formed in two different industrially relevant ways. Firstly, dry granulation was used to produce pellets which were sieved to give material with a 300-1000 μm size, and the fines were subsequently recycled to mimic a large scale industrial process. Secondly, wet granulation with a polymer was used to produce granules which were again sieved to 300-1000 μm. XRD data shows that the structures of MIL-100(Fe) and CPO-27(Ni) remain intact during both forming processes, whilst Cu-BTC is shown to degrade during processing. This is in line with the ammonia adsorption data obtained for the formed materials which evaluated the ammonia adsorption capacity of the materials using breakthrough measurements. MIL-100(Fe) and CPO-27(Ni) are shown to have capacities of 47 mg g -1 and 62 mg g -1 respectively whilst Cu-BTC has a decreased capacity of 37 mg g -1 from 97 mg g -1 upon forming. The formed materials were also aged at 25 °C and 80% humidity for a week and the ammonia adsorption capacity re-evaluated. As expected, Cu-BTC decomposed under these conditions, whilst MIL-100(Fe) and CPO-27(Ni) show slightly decreased ammonia adsorption capacities of 36 mg g -1 and 60 mg g -1 respectively.

Hypoglycemic activity of dried extracts of Bauhinia forficata Link.

PubMed

da Cunha, A M; Menon, S; Menon, R; Couto, A G; Bürger, C; Biavatti, M W

2010-01-01

Leaves of the pantropical genus Bauhinia (Fabaceae) are known popularly as cow's foot, due to their unique characteristic bilobed aspect. The species Bauhinia forficata (Brazilian Orchid-tree) is widely used in folk medicine as an antidiabetic. The present work investigates the hypoglycemic activity of the dried extracts of Bauhinia forficata leaves in vivo, as well as the influence of the drying and granulation processes on this activity. The fluid extract was dried to generate oven-dried (ODE), spray-dried (SDE) and wet granulation (WGE) extracts, with the aid of colloidal silicon dioxide and/or cellulose:lactose mixture. The dried extracts were characterized by spectrophotometric, chromatographic and photo microscopy image analysis. 200 mg/kg body wt., p.o. of each dried product were administered orally to male Wistar rats over 7 days old, for biomonitoring of the hypoglycemic activity profile. The effect of the extracts was studied in STZ-induced diabetic rats. After 7 days of treatment, fasting glucose was determined, and the livers were removed, dried on tissue paper, weighed, and stored at -20 degrees C to estimate hepatic glycogen. Our results show that spray-drying or oven-drying processes applied to B. forficata extracts did not significantly alter its flavonoid profile or its hypoglycemic activity. Indeed, the dried extracts of B. forficata act differently from glibenclamide. Despite the lower active content in WGE, because of the higher concentration of adjuvants, the use of the granulation process improved the manufacturing properties of the ODE, making this material more appropriate for use in tablets or capsules.

Comparison of the efficacy of dispensing granules with traditional decoction: a systematic review and meta-analysis

PubMed Central

Qiu, Ruijin; Zhang, Xiaoyu; Zhao, Chen; Li, Min

2018-01-01

Background Dispensing granules have been developed for about 20 years. However, whether they are as effective as the traditional decoction kept unclear. This systematic review and meta-analysis was made to assess the efficacy of dispensing granules compared with traditional decoction. Methods We searched four databases since their inception to 9th September in 2016. Two authors independently identified trials, extracted data and assessed risk of bias with Cochrane Reviewer’s Handbook 5.0. We conducted meta-analysis with RevMan 5.1.0 software for eligible and appropriate trials. Results In the end, 7,035 participants from 51 randomized controlled trials (RCTs) which compared dispensing granules with traditional decoction were included in this systematic review. There were 33 different kinds of diseases for investigation, of which 8 RCTs observed common cold, 4 RCTs observed migraine. For rheumatoid arthritis, insomnia and hypertension, there were 3 RCTs reported respectively. The last RCTs reported different kinds of diseases in one or two trials. The majority of trials were in low methodological quality. Thirty-eight (74.5%) RCTs showed that the efficacy of dispensing granules were similar with traditional decoction, 6 (11.8%) RCTs reported that the therapeutic efficacy of dispensing granules were significantly better than traditional decoction. We conducted meta-analysis for 4 trials investigating patients with migraine. The results showed that dispensing granules reduced headache frequency by about 1.03 attacks per month as compared to traditional decoction. No evidence was found in terms of migraine intensity and duration. Conclusions The low quality of RCTs and conflicting results made it difficult to draw a definite conclusion. In the future, it needs much more evidence to explore the efficacy and safety of dispensing granules. N-of-1 trials and fuzzy comprehensive evaluation methods may be better choices for assessing the efficacy of them than RCTs. PMID:29610730

Chromospheric impact of an exploding solar granule

NASA Astrophysics Data System (ADS)

Fischer, C. E.; Bello González, N.; Rezaei, R.

2017-06-01

Context. Observations of multi-wavelength and therefore height-dependent information following events throughout the solar atmosphere and unambiguously assigning a relation between these rapidly evolving layers are rare and difficult to obtain. Yet, they are crucial for our understanding of the physical processes that couple the different regimes in the solar atmosphere. Aims: We characterize the exploding granule event with simultaneous observations of Hinode spectroplarimetric data in the solar photosphere and Hinode broadband Ca II H images combined with Interface Region Imaging Spectrograph (IRIS) slit spectra. We follow the evolution of an exploding granule and its connectivity throughout the atmosphere and analyze the dynamics of a magnetic element that has been affected by the abnormal granule. Methods: In addition to magnetic flux maps we use a local correlation tracking method to infer the horizontal velocity flows in the photosphere and apply a wavelet analysis on several IRIS chromospheric emission features such as Mg II k2v and Mg II k3 to detect oscillatory phenomena indicating wave propagation. Results: During the vigorous expansion of the abnormal granule we detect radially outward horizontal flows, causing, together with the horizontal flows from the surrounding granules, the magnetic elements in the bordering intergranular lanes to be squeezed and elongated. In reaction to the squeezing, we detect a chromospheric intensity and velocity oscillation pulse which we identify as an upward traveling hot shock front propagating clearly through the IRIS spectral line diagnostics of Mg II h&k. Conclusions: Exploding granules can trigger upward-propagating shock fronts that dissipate in the chromosphere. Movies associated to Figs. A.1 and A.2 are available in electronic form at http://www.aanda.org

Granular activated carbon as nucleating agent for aerobic sludge granulation: Effect of GAC size on velocity field differences (GAC versus flocs) and aggregation behavior.

PubMed

Zhou, Jia-Heng; Zhao, Hang; Hu, Miao; Yu, Hai-Tian; Xu, Xiang-Yang; Vidonish, Julia; Alvarez, Pedro J J; Zhu, Liang

2015-12-01

Initial cell aggregation plays an important role in the formation of aerobic granules. In this study, three parallel aerobic granular sludge reactors treating low-strength wastewater were established using granular activated carbon (GAC) of different sizes as the nucleating agent. A novel visual quantitative evaluation method was used to discern how GAC size affects velocity field differences (GAC versus flocs) and aggregation behavior during sludge granulation. Results showed that sludge granulation was significantly enhanced by addition of 0.2mm GAC. However, there was no obvious improvement in granulation in reactor amended with 0.6mm GAC. Hydraulic analysis revealed that increase of GAC size enhanced the velocity field difference between flocs and GAC, which decreased the lifecycle and fraction of flocs-GAC aggregates. Overall, based on analysis of aggregation behavior, GAC of suitable sizes (0.2mm) can serve as the nucleating agent to accelerate flocs-GAC coaggregation and formation of aerobic granules. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ultrastructure of the platypus and echidna mandibular glands.

PubMed

Krause, W J

2011-10-01

The secretory units of the platypus and echidna mandibular glands consist of a single serous cell type. Secretory granules within the cells of the platypus mandibular gland stained intensely with the periodic acid-Schiff staining procedure but failed to stain with Alcian Blue, suggesting the granules contained neutral glycoproteins. Secretory granules within the mandibular glands of the echidna failed to stain with the methods used indicating little if any glycoprotein was associated with the secretory granules. Ultrastructurally, secretory granules of the platypus mandibular gland were electron dense with a central core of less electron-dense material and were membrane bound. In contrast, those of the echidna presented a lamellated appearance and also were limited by a membrane. These secretory granules appeared to form as a result of concentric layering of lamellae within cisternae of the Golgi membranes. The intralobular ductal system of the platypus was more extensively developed than that of the echidna. The striated ducts of both species were characterized by elaborate infoldings of the basolateral plasmalemma and an abundance of associated mitochondria. © 2011 Blackwell Verlag GmbH.

[Modification of Bowie's method of demonstrating specific granules in cells of the human renal juxtaglomerular apparatus fixed in neutral formalin].

PubMed

Orduian, S L

1976-04-01

A modification of Bowie's method for detection of specific granules of the juxtaglomerular apparatus of the human kidneys, fixed in 10% neutral formalin, is suggested. In order to achieve better staining, sections of material fixed in formalin are additionally treated with Helly's liquid and, following the removal of sublimate deposit, with a 2.5% solution of potassium bichromate. After this the sections are stained by Bowie's method in accordance with Pitcock and Hartroft's prescription.

Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design.

PubMed

Morovati, Amirhosein; Ghaffari, Alireza; Erfani Jabarian, Lale; Mehramizi, Ali

2017-01-01

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex ® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release "%" in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X 1 : Cetyl alcohol, X 2 : Starch 1500 ® , X 3 : HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X 1 : 37.10, X 2 : 2, X 3 : 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500 ® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too.

Single Layer Extended Release Two-in-One Guaifenesin Matrix Tablet: Formulation Method, Optimization, Release Kinetics Evaluation and Its Comparison with Mucinex® Using Box-Behnken Design

PubMed Central

Morovati, Amirhosein; Ghaffari, Alireza; Erfani jabarian, Lale; Mehramizi, Ali

2017-01-01

Guaifenesin, a highly water-soluble active (50 mg/mL), classified as a BCS class I drug. Owing to its poor flowability and compressibility, formulating tablets especially high-dose one, may be a challenge. Direct compression may not be feasible. Bilayer tablet technology applied to Mucinex®, endures challenges to deliver a robust formulation. To overcome challenges involved in bilayer-tablet manufacturing and powder compressibility, an optimized single layer tablet prepared by a binary mixture (Two-in-one), mimicking the dual drug release character of Mucinex® was purposed. A 3-factor, 3-level Box-Behnken design was applied to optimize seven considered dependent variables (Release “%” in 1, 2, 4, 6, 8, 10 and 12 h) regarding different levels of independent one (X1: Cetyl alcohol, X2: Starch 1500®, X3: HPMC K100M amounts). Two granule portions were prepared using melt and wet granulations, blended together prior to compression. An optimum formulation was obtained (X1: 37.10, X2: 2, X3: 42.49 mg). Desirability function was 0.616. F2 and f1 between release profiles of Mucinex® and the optimum formulation were 74 and 3, respectively. An n-value of about 0.5 for both optimum and Mucinex® formulations showed diffusion (Fickian) control mechanism. However, HPMC K100M rise in 70 mg accompanied cetyl alcohol rise in 60 mg led to first order kinetic (n = 0.6962). The K values of 1.56 represented an identical burst drug releases. Cetyl alcohol and starch 1500® modulated guaifenesin release from HPMC K100M matrices, while due to their binding properties, improved its poor flowability and compressibility, too. PMID:29552045

Catharanthus roseus flower extract has wound-healing activity in Sprague Dawley rats

PubMed Central

Nayak, BS; Pinto Pereira, Lexley M

2006-01-01

Background Catharanthus roseus L (C. roseus) has been used to treat a wide assortment of diseases including diabetes. The objective of our study was to evaluate the antimicrobial and wound healing activity of the flower extract of Catharanthus in rats. Methods Wound healing activity was determined in rats, after administration (100 mg kg-1 day-1) of the ethanol extract of C. roseus flower, using excision, incision and dead space wounds models. The animals were divided into two groups of 6 each in all the models. In the excision model, group 1 animals were topically treated with carboxymethyl cellulose as placebo control and group 2 received topical application of the ethanol extract of C. roseus at a dose of 100 mg/kg body weight/day. In an incision and dead space model group 1 animals were given normal saline and group 2 received the extract orally at a dose of 100 mg kg-1 day-1. Healing was assessed by the rate of wound contraction, period of epithelization, tensile strength (skin breaking strength), granulation tissue weight, and hydoxyproline content. Antimicrobial activity of the flower extract against four microorganisms was also assessed Results The extract of C. roseus significantly increased the wound breaking strength in the incision wound model compared with controls (P < 0.001). The extract-treated wounds were found to epithelialize faster, and the rate of wound contraction was significantly increased in comparison to control wounds (P < 0.001), Wet and dry granulation tissue weights, and hydroxyproline content in a dead space wound model increased significantly (p < 0.05). Pseudomonas aeruginosa and Staphylococcus aureus demonstrated sensitivity to C. roseus Conclusion Increased wound contraction and tensile strength, augmented hydroxyproline content along with antimicrobial activity support the use of C. roseus in the topical management of wound healing. PMID:17184528

Vigorous convection in a sunspot granular light bridge

NASA Astrophysics Data System (ADS)

Lagg, Andreas; Solanki, Sami K.; van Noort, Michiel; Danilovic, Sanja

2014-08-01

Context. Light bridges are the most prominent manifestation of convection in sunspots. The brightest representatives are granular light bridges composed of features that appear to be similar to granules. Aims: An in-depth study of the convective motions, temperature stratification, and magnetic field vector in and around light bridge granules is presented with the aim of identifying similarities and differences to typical quiet-Sun granules. Methods: Spectropolarimetric data from the Hinode Solar Optical Telescope were analyzed using a spatially coupled inversion technique to retrieve the stratified atmospheric parameters of light bridge and quiet-Sun granules. Results: Central hot upflows surrounded by cooler fast downflows reaching 10 km s-1 clearly establish the convective nature of the light bridge granules. The inner part of these granules in the near surface layers is field free and is covered by a cusp-like magnetic field configuration. We observe hints of field reversals at the location of the fast downflows. The quiet-Sun granules in the vicinity of the sunspot are covered by a low-lying canopy field extending radially outward from the spot. Conclusions: The similarities between quiet-Sun and light bridge granules point to the deep anchoring of granular light bridges in the underlying convection zone. The fast, supersonic downflows are most likely a result of a combination of invigorated convection in the light bridge granule due to radiative cooling into the neighboring umbra and the fact that we sample deeper layers, since the downflows are immediately adjacent to the slanted walls of the Wilson depression. The two movies are available in electronic form at http://www.aanda.org

Localization of DNA and RNA in eosinophil secretory granules.

PubMed

Behzad, Ali R; Walker, David C; Abraham, Thomas; McDonough, John; Mahmudi-Azer, Salahadin; Chu, Fanny; Shaheen, Furquan; Hogg, James C; Paré, Peter D

2010-01-01

Although the accepted paradigm is that the proteins stored in eosinophil crystalloid granules are translated from messenger RNA transcribed in the cell nucleus, recent ultrastructural evidence suggests that protein synthesis may also take place within eosinophilic granules. We used 2 different methods to detect the presence of DNA and RNA in eosinophil secretory granules. Using bromodeoxyuridine, a thymidine analogue, and bromouridine, a uracil analogue, we labeled the DNA and RNA in eosinophils in vivo in rabbits. Immunoelectron microscopy to localize these molecules was performed on ultrathin sections of blood and bone marrow eosinophils using monoclonal anti-bromodeoxyuridine antibody with IgG as a control. The immunogold grain density was measured in each subcellular compartment within the eosinophils and analyzed using image analysis software. A combination of DNA/CD63 immunofluorescence staining and a fluorescently labeled molecular probe that stains RNA was used to examine the presence of DNA and RNA in the secretory granules of human blood eosinophils. The mean density of bromodeoxyuridine-labeled DNA and bromouridine-labeled RNA immunogold grains in the secretory granules of blood and bone marrow eosinophils were significantly higher (p < 0.0005) than cytoplasmic or background staining. We also demonstrated the existence of DNA and RNA in the CD63-positive secretory granules of human peripheral blood eosinophils by means of immunofluorescent staining and a fluorescently labeled molecular probe. These results provide evidence that eosinophil granules are the site of DNA and RNA synthesis and suggest the potential for a new role(s) for eosinophil-secretory granules. Copyright 2009 S. Karger AG, Basel.

First Results of ELM Triggering With a Multichamber Lithium Granule Injector Into EAST Discharges

DOE PAGES

Sun, Z.; Lunsford, R.; Maingi, R.; ...

2017-12-12

A critical challenge facing the basic long-pulse H-mode for ITER is to control edge-localized modes (ELMs). A new method using a multichamber lithium (Li) granule injector (LGI) for ELM triggering experiments has been developed in Experimental Advanced Superconducting Tokamak (EAST). First experimental results of the control of ELMs are obtained in EAST with a tungsten divertor. It is found that the injector has good capacities, i.e., allowing good flexibilities in granule size selection, injection rate, and injection velocity. In conclusion, LGI has successfully triggered ELMs during the H-mode. These results indicate the LGI would be a promising method to controlmore » ELMs in long-pulse steady-state tokamaks.« less

First Results of ELM Triggering With a Multichamber Lithium Granule Injector Into EAST Discharges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Z.; Lunsford, R.; Maingi, R.

A critical challenge facing the basic long-pulse H-mode for ITER is to control edge-localized modes (ELMs). A new method using a multichamber lithium (Li) granule injector (LGI) for ELM triggering experiments has been developed in Experimental Advanced Superconducting Tokamak (EAST). First experimental results of the control of ELMs are obtained in EAST with a tungsten divertor. It is found that the injector has good capacities, i.e., allowing good flexibilities in granule size selection, injection rate, and injection velocity. In conclusion, LGI has successfully triggered ELMs during the H-mode. These results indicate the LGI would be a promising method to controlmore » ELMs in long-pulse steady-state tokamaks.« less

[Investigation on production process quality control of traditional Chinese medicine--Banlangen granule as an example].

PubMed

Tan, Manrong; Yan, Dan; Qiu, Lingling; Chen, Longhu; Yan, Yan; Jin, Cheng; Li, Hanbing; Xiao, Xiaohe

2012-04-01

For the quality management system of herbal medicines, intermediate and finished products it exists the " short board" effect of methodologies. Based on the concept of process control, new strategies and new methods of the production process quality control had been established with the consideration of the actual production of traditional Chinese medicine an the characteristics of Chinese medicine. Taking Banlangen granule as a practice example, which was effective and widespread application, character identification, determination of index components, chemical fingerprint and biometrics technology were sequentially used respectively to assess the quality of Banlangen herbal medicines, intermediate (water extraction and alcohol precipitation) and finished product. With the transfer rate of chemical information and biological potency as indicators, the effectiveness and transmission of the above different assessments and control methods had been researched. And ultimately, the process quality control methods of Banlangen granule, which were based on chemical composition analysis-biometric analysis, had been set up. It can not only validly solute the current status that there were many manufacturers varying quality of Banlangen granule, but also ensure and enhance its clinical efficacy. Furthermore it provided a foundation for the construction of the quality control of traditional Chinese medicine production process.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2002-11-01

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve. At the initial stage, PPA was released from the gel layer of swollen EC in the matrix granules. At the second stage, the drug existing below the gel layer dissolved, and was released through the gel layer. Also, the time and release ratio at the connection point of the simulation curves was examined to determine the validity of the analysis. Comparing the release properties of PPA from the two types of EC matrix granules, EC#100 showed more effective sustained release than EC#10. On the other hand, changes in the release property of the EC#10 matrix granule were relatively more clear than that of the EC#100 matrix granule. Thus, it was supposed that EC#10 is more available for controlled and sustained release formulations than EC#100.

Three-dimensional ultrastructural analyses of anterior pituitary gland expose spatial relationships between endocrine cell secretory granule localization and capillary distribution.

PubMed

Yoshitomi, Munetake; Ohta, Keisuke; Kanazawa, Tomonoshin; Togo, Akinobu; Hirashima, Shingo; Uemura, Kei-Ichiro; Okayama, Satoko; Morioka, Motohiro; Nakamura, Kei-Ichiro

2016-10-31

Endocrine and endothelial cells of the anterior pituitary gland frequently make close appositions or contacts, and the secretory granules of each endocrine cell tend to accumulate at the perivascular regions, which is generally considered to facilitate secretory functions of these cells. However, three-dimensional relationships between the localization pattern of secretory granules and blood vessels are not fully understood. To define and characterize these spatial relationships, we used scanning electron microscopy (SEM) three-dimensional reconstruction method based on focused ion-beam slicing and scanning electron microscopy (FIB/SEM). Full three-dimensional cellular architectures of the anterior pituitary tissue at ultrastructural resolution revealed that about 70% of endocrine cells were in apposition to the endothelial cells, while almost 30% of endocrine cells were entirely isolated from perivascular space in the tissue. Our three-dimensional analyses also visualized the distribution pattern of secretory granules in individual endocrine cells, showing an accumulation of secretory granules in regions in close apposition to the blood vessels in many cases. However, secretory granules in cells isolated from the perivascular region tended to distribute uniformly in the cytoplasm of these cells. These data suggest that the cellular interactions between the endocrine and endothelial cells promote an uneven cytoplasmic distribution of the secretory granules.

Prolonged release matrix tablet of pyridostigmine bromide: formulation and optimization using statistical methods.

PubMed

Bolourchian, Noushin; Rangchian, Maryam; Foroutan, Seyed Mohsen

2012-07-01

The aim of this study was to design and optimize a prolonged release matrix formulation of pyridostigmine bromide, an effective drug in myasthenia gravis and poisoning with nerve gas, using hydrophilic - hydrophobic polymers via D-optimal experimental design. HPMC and carnauba wax as retarding agents as well as tricalcium phosphate were used in matrix formulation and considered as independent variables. Tablets were prepared by wet granulation technique and the percentage of drug released at 1 (Y(1)), 4 (Y(2)) and 8 (Y(3)) hours were considered as dependent variables (responses) in this investigation. These experimental responses were best fitted for the cubic, cubic and linear models, respectively. The optimal formulation obtained in this study, consisted of 12.8 % HPMC, 24.4 % carnauba wax and 26.7 % tricalcium phosphate, had a suitable prolonged release behavior followed by Higuchi model in which observed and predicted values were very close. The study revealed that D-optimal design could facilitate the optimization of prolonged release matrix tablet containing pyridostigmine bromide. Accelerated stability studies confirmed that the optimized formulation remains unchanged after exposing in stability conditions for six months.

Frosta: a new technology for making fast-melting tablets.

PubMed

Jeong, Seong Hoon; Fu, Yourong; Park, Kinam

2005-11-01

The fast-melting tablet (FMT) technology, which is known to be one of the most innovated methods in oral drug delivery systems, is a rapidly growing area of drug delivery. The initial success of the FMT formulation led to the development of various technologies. These technologies, however, still have some limitations. Recently, a new technology called Frosta (Akina) was developed for making FMTs. The Frosta technology utilises the conventional wet granulation process and tablet press for cost-effective production of tablets. The Frosta tablets are mechanically strong with friability of < 1% and are stable in accelerated stability conditions when packaged into a bottle container. They are robust enough to be packaged in multi-tablet vials. Conventional rotary tablet presses can be used for the production of the tablets and no other special instruments are required. Thus, the cost of making FMTs is lower than that of other existing technologies. Depending on the size, Frosta tablets can melt in < 10 s after placing them in the oral cavity for easy swallowing. The Frosta technology is ideal for wide application of FMTs technology to various drug and nutritional formulations.

Optimization of poorly compactable drug tablets manufactured by direct compression using the mixture experimental design.

PubMed

Martinello, Tiago; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Taqueda, Maria Elena Santos; Consiglieri, Vladi O

2006-09-28

The poor flowability and bad compressibility characteristics of paracetamol are well known. As a result, the production of paracetamol tablets is almost exclusively by wet granulation, a disadvantageous method when compared to direct compression. The development of a new tablet formulation is still based on a large number of experiments and often relies merely on the experience of the analyst. The purpose of this study was to apply experimental design methodology (DOE) to the development and optimization of tablet formulations containing high amounts of paracetamol (more than 70%) and manufactured by direct compression. Nineteen formulations, screened by DOE methodology, were produced with different proportions of Microcel 102, Kollydon VA 64, Flowlac, Kollydon CL 30, PEG 4000, Aerosil, and magnesium stearate. Tablet properties, except friability, were in accordance with the USP 28th ed. requirements. These results were used to generate plots for optimization, mainly for friability. The physical-chemical data found from the optimized formulation were very close to those from the regression analysis, demonstrating that the mixture project is a great tool for the research and development of new formulations.

[Quality evaluation of rhubarb dispensing granules based on multi-component simultaneous quantitative analysis and bioassay].

PubMed

Tan, Peng; Zhang, Hai-Zhu; Zhang, Ding-Kun; Wu, Shan-Na; Niu, Ming; Wang, Jia-Bo; Xiao, Xiao-He

2017-07-01

This study attempts to evaluate the quality of Chinese formula granules by combined use of multi-component simultaneous quantitative analysis and bioassay. The rhubarb dispensing granules were used as the model drug for demonstrative study. The ultra-high performance liquid chromatography (UPLC) method was adopted for simultaneously quantitative determination of the 10 anthraquinone derivatives (such as aloe emodin-8-O-β-D-glucoside) in rhubarb dispensing granules; purgative biopotency of different batches of rhubarb dispensing granules was determined based on compound diphenoxylate tablets-induced mouse constipation model; blood activating biopotency of different batches of rhubarb dispensing granules was determined based on in vitro rat antiplatelet aggregation model; SPSS 22.0 statistical software was used for correlation analysis between 10 anthraquinone derivatives and purgative biopotency, blood activating biopotency. The results of multi-components simultaneous quantitative analysisshowed that there was a great difference in chemical characterizationand certain differences inpurgative biopotency and blood activating biopotency among 10 batches of rhubarb dispensing granules. The correlation analysis showed that the intensity of purgative biopotency was significantly correlated with the content of conjugated anthraquinone glycosides (P<0.01), and the intensity of blood activating biopotency was significantly correlated with the content of free anthraquinone (P<0.01). In summary, the combined use of multi-component simultaneous quantitative analysis and bioassay can achieve objective quantification and more comprehensive reflection on overall quality difference among different batches of rhubarb dispensing granules. Copyright© by the Chinese Pharmaceutical Association.

Polymorphic Transformation of Indomethacin during Hot Melt Extrusion Granulation: Process and Dissolution Control.

PubMed

Xu, Ting; Nahar, Kajalajit; Dave, Rutesh; Bates, Simon; Morris, Kenneth

2018-05-10

To study and elucidate the effect of the intensity and duration of processing stresses on the possible solid-state changes during a hot melt extrusion granulation process. Blends of α-indomethacin and PEG 3350 (w/w 4:1) were granulated using various screw sizes/designs on the melt extruder under different temperature regimes. Differential Scanning Calorimetry and X-ray Powder Diffraction were employed for characterization. The dissolution behavior of the pure polymorphs and the resulting granules was determined using in-situ fiber optic UV testing system. An XRPD quantitation method using Excel full pattern fitting was developed to determine the concentration of each constituent (amorphous, α and γ indomethacin and PEG) in samples collected from each functioning zone and in granules. Analysis of in-process samples and granules revealed that higher temperature (≥130°C) and shear stress accelerated the process induced phase transitions from amorphous and/or the α form to γ indomethacin during heating stage. However, rapid cooling resulted in an increased percentage of the α form allowing isolation of the meta-stable form. By determining the conditions that either prevent or facilitate process induced transformations of IMC polymorphs during melt granulation, a design space was developed to control the polymorph present in the resulting granules. This represents the conditions necessary to balance the thermodynamic relationships between the polymorphs of the IMC system and the kinetics of the possible transformations as a function of the processing stresses.

Combining µXANES and µXRD mapping to analyse the heterogeneity in calcium carbonate granules excreted by the earthworm Lumbricus terrestris

PubMed Central

Brinza, Loredana; Schofield, Paul F.; Hodson, Mark E.; Weller, Sophie; Ignatyev, Konstantin; Geraki, Kalotina; Quinn, Paul D.; Mosselmans, J. Frederick W.

2014-01-01

The use of fluorescence full spectral micro-X-ray absorption near-edge structure (µXANES) mapping is becoming more widespread in the hard energy regime. This experimental method using the Ca K-edge combined with micro-X-ray diffraction (µXRD) mapping of the same sample has been enabled on beamline I18 at Diamond Light Source. This combined approach has been used to probe both long- and short-range order in calcium carbonate granules produced by the earthworm Lumbricus terrestris. In granules produced by earthworms cultured in a control artificial soil, calcite and vaterite are observed in the granules. However, granules produced by earthworms cultivated in the same artificial soil amended with 500 p.p.m. Mg also contain an aragonite. The two techniques, µXRD and µXANES, probe different sample volumes but there is good agreement in the phase maps produced. PMID:24365942

Numerical modeling of the tensile strength of a biological granular aggregate: Effect of the particle size distribution

NASA Astrophysics Data System (ADS)

Heinze, Karsta; Frank, Xavier; Lullien-Pellerin, Valérie; George, Matthieu; Radjai, Farhang; Delenne, Jean-Yves

2017-06-01

Wheat grains can be considered as a natural cemented granular material. They are milled under high forces to produce food products such as flour. The major part of the grain is the so-called starchy endosperm. It contains stiff starch granules, which show a multi-modal size distribution, and a softer protein matrix that surrounds the granules. Experimental milling studies and numerical simulations are going hand in hand to better understand the fragmentation behavior of this biological material and to improve milling performance. We present a numerical study of the effect of granule size distribution on the strength of such a cemented granular material. Samples of bi-modal starch granule size distribution were created and submitted to uniaxial tension, using a peridynamics method. We show that, when compared to the effects of starch-protein interface adhesion and voids, the granule size distribution has a limited effect on the samples' yield stress.

Live cell imaging of Argonaute proteins in mammalian cells.

PubMed

Pare, Justin M; Lopez-Orozco, Joaquin; Hobman, Tom C

2011-01-01

The central effector of mammalian RNA interference (RNAi) is the RNA-induced silencing complex (RISC). Proteins of the Argonaute family are the core components of RISC. Recent work from multiple laboratories has shown that Argonaute family members are associated with at least two types of cytoplasmic RNA granules: GW/Processing bodies and stress granules. These Argonaute-containing granules harbor proteins that function in mRNA degradation and translational repression in response to stress. The known role of Argonaute proteins in miRNA-mediated translational repression and siRNA-directed mRNA cleavage (i.e., Argonaute 2) has prompted speculation that the association of Argonautes with these granules may reflect the activity of RNAi in vivo. Accordingly, studying the dynamic association between Argonautes and RNA granules in living cells will undoubtedly provide insight into the regulatory mechanisms of RNA-based silencing. This chapter describes a method for imaging fluorescently tagged Argonaute proteins in living mammalian cells using spinning disk confocal microscopy.

Experimental and numerical characterization of expanded glass granules

NASA Astrophysics Data System (ADS)

Chaudry, Mohsin Ali; Woitzik, Christian; Düster, Alexander; Wriggers, Peter

2018-07-01

In this paper, the material response of expanded glass granules at different scales and under different boundary conditions is investigated. At grain scale, single particle tests can be used to determine properties like Young's modulus or crushing strength. With experiments like triaxial and oedometer tests, it is possible to examine the bulk mechanical behaviour of the granular material. Our experimental investigation is complemented by a numerical simulation where the discrete element method is used to compute the mechanical behaviour of such materials. In order to improve the simulation quality, effects such as rolling resistance, inelastic behaviour, damage, and crushing are also included in the discrete element method. Furthermore, the variation of the material properties of granules is modelled by a statistical distribution and included in our numerical simulation.

Study on the Multi-marker Components Quantitative HPLC Fingerprint of the Compound Chinese Medicine Wuwei Changyanning Granule

PubMed Central

Yang, Xian; Yang, Shui-Ping; Zhang, Xue; Yu, Xiao-Dong; He, Qi-Yi; Wang, Bo-Chu

2014-01-01

The aim of this paper is to develop a rapid and highly sensitive quantitative HPLC fingerprint method with multiple indicators by using the Compound Chinese Medicine Wuwei Changyanning granule and 5 herbs in the prescription. The quantitative fingerprint chromatogram with multiple indicators was investigated. і)6 compositions included rutin, gallic acid, chlorogenic acid, atractylenolide Ⅰ, pachymic acid and apigenin, which originated from 5 herbs respectively, were selected as quantitative compositions, and their contents were determined using HPLC from 11 batches granules and the corresponding 5 medicinal materials. ⅱ) The precision, stability and repeatability of fingerprinting were investigated. In addition, common peaks number, the percentage of non-common peaks and similarity were also studied. Among them, 21 common peaks in the granule could find the source of peaks from the 5 herbs, among of 10 peaks from Niuerfeng, 9 peaks from Laliao, 3 peaks from Baishu, 3 peaks from Fuling and 5 peaks from Guanghuoxiang. The results showed that the identification method of fingerprinting was reliable. PMID:25587307

Investigation of Dissolution Behavior HPMC/Eudragit®/Magnesium Aluminometasilicate Oral Matrices Based on NMR Solid-State Spectroscopy and Dynamic Characteristics of Gel Layer.

PubMed

Naiserová, M; Kubová, K; Vysloužil, J; Pavloková, S; Vetchý, D; Urbanová, M; Brus, J; Vysloužil, J; Kulich, P

2018-02-01

Burst drug release is often considered a negative phenomenon resulting in unexpected toxicity or tissue irritation. Optimal release of a highly soluble active pharmaceutical ingredient (API) from hypromellose (HPMC) matrices is technologically impossible; therefore, a combination of polymers is required for burst effect reduction. Promising variant could be seen in combination of HPMC and insoluble Eudragits ® as water dispersions. These can be applied only on API/insoluble filler mixture as over-wetting prevention. The main hurdle is a limited water absorption capacity (WAC) of filler. Therefore, the object of this study was to investigate the dissolution behavior of levetiracetam from HPMC/Eudragit ® NE matrices using magnesium aluminometasilicate (Neusilin ® US2) as filler with excellent WAC. Part of this study was also to assess influence of thermal treatment on quality parameters of matrices. The use of Neusilin ® allowed the application of Eudragit ® dispersion to API/Neusilin ® mixture in one step during high-shear wet granulation. HPMC was added extragranularly. Obtained matrices were investigated for qualitative characteristics, NMR solid-state spectroscopy (ssNMR), gel layer dynamic parameters, SEM, and principal component analysis (PCA). Decrease in burst effect (max. of 33.6%) and dissolution rate, increase in fitting to zero-order kinetics, and paradoxical reduction in gel layer thickness were observed with rising Eudragit ® NE concentration. The explanation was done by ssNMR, which clearly showed a significant reduction of the API particle size (150-500 nm) in granules as effect of surfactant present in dispersion in dependence on Eudragit ® NE amount. This change in API particle size resulted in a significantly larger interface between these two entities. Based on ANOVA and PCA, thermal treatment was not revealed as a useful procedure for this system.

Peroxisomes in the nervous system of Aplysia californica: a cytochemical study.

PubMed

Beard, M E; Holtzman, E

1985-08-01

We have studied the distribution of peroxisomes in the abdominal ganglion of Aplysia californica using electron microscopic cytochemical methods. Reaction product for catalase was observed in small ovoid or dumb-bell-shaped bodies in the perikarya of many of the neurons. The abundance of these catalase-reactive peroxisomes is considerably greater than is the case in vertebrate neurons. While the non-neuronal cells of the Aplysia abdominal ganglion do contain appreciable peroxisome populations, there were few peroxisomes in glial cytoplasm directly adjacent to the perikarya, again contrasting with vertebrate ganglia in which the satellite cells are a principal site of peroxisomes. Peroxisomes are present throughout the perikaryal cytoplasm. In the regions in which lipochrome granules abound, peroxisomes are frequently seen closely associated with these granules; glycogen is abundant nearby. The association of peroxisomes, lipochrome granules and glycogen is interesting in view of the propinquities of peroxisomes to lipid droplets and lipofuscin granules reported for non-neuronal vertebrate tissues, and in view of the growing evidence indicating that some of the roles of peroxisomes are in lipid metabolism and in gluconeogenesis. Some of the lipochrome granules themselves show reaction product in ganglia incubated to demonstrate catalase activity and some react in tissue incubated to demonstrate acid phosphatase activity. Such observations suggest that the enzymatic capacities of the lipochrome granules merit further studies, and that the granules may be of complex or heterogeneous nature.

Artificial neural network modelling for organic and total nitrogen removal of aerobic granulation under steady-state condition.

PubMed

Gong, H; Pishgar, R; Tay, J H

2018-04-27

Aerobic granulation is a recent technology with high level of complexity and sensitivity to environmental and operational conditions. Artificial neural networks (ANNs), computational tools capable of describing complex non-linear systems, are the best fit to simulate aerobic granular bioreactors. In this study, two feedforward backpropagation ANN models were developed to predict chemical oxygen demand (Model I) and total nitrogen removal efficiencies (Model II) of aerobic granulation technology under steady-state condition. Fundamentals of ANN models and the steps to create them were briefly reviewed. The models were respectively fed with 205 and 136 data points collected from laboratory-, pilot-, and full-scale studies on aerobic granulation technology reported in the literature. Initially, 60%, 20%, and 20%, and 80%, 10%, and 10% of the points in the corresponding datasets were randomly chosen and used for training, testing, and validation of Model I, and Model II, respectively. Overall coefficient of determination (R 2 ) value and mean squared error (MSE) of the two models were initially 0.49 and 15.5, and 0.37 and 408, respectively. To improve the model performance, two data division methods were used. While one method is generic and potentially applicable to other fields, the other can only be applied to modelling the performance of aerobic granular reactors. R 2 value and MSE were improved to 0.90 and 2.54, and 0.81 and 121.56, respectively, after applying the new data division methods. The results demonstrated that ANN-based models were capable simulation approach to predict a complicated process like aerobic granulation.

Outgassing of planets in relation to their obital frequencies

NASA Astrophysics Data System (ADS)

Kochemasov, G.

Planetary atmospheres as inseparable parts of their geospheres have close structural and compositional ties with underlying solid formations. The comparative wave planetology having stated that "orbits make structures" finds that two fundamental properties of all celestial bodies are most important for their structurization: movement and rotation. All bodies move in non-round keplerian elliptic (and parabolic) orbits that implies periodic change of accelerations and delivery of inertia-gravity forces producing warping waves. In rotating bodies (but all celestial bodies rotate !) these waves are ordered in 4 ortho- and diagonal directions. Having stationary character and various lengths they interfere producing positive (+), negative (-) and neutral (0) tectonic blocks. The fundamental wave 1 long 2πR give ubiquitous tectonic dichotomy, the first overtone wave 2 makes tectonic sectoring. Individual for any body waves whose lengths are inversely proportional to their orbital frequencies produce tectonic granules: higher frequency - smaller granule. The following row shows increasing granule sizes (a half of a wavelength, Earth as a scale): Titan πR/91, Mercury πR/16, Venus πR/6, Earth πR/4, Mars πR/2, asteroids πR/1. One may say that Venus is tectonically "fine-grained", Earth "medium-grained", Mars "coarse-grained". The wave produced granulation indicates that fine-grained Venus is more thoroughly shaken out and released of its volatiles (degassed) than Earth and Mars. This is proved by its massive atmosphere containing a large amount of nitrogen and having very low ratio of radiogenic to primordial argon (Venus 1, Earth 300, Mars 3000). Compare "sweeping" volatiles out of Venus and Earth [1]. Venus is 3.38 times finer-grained than Earth (in the terrestrial globe there are 16.5 grains of radius πR/8, in the venusian one 55.7 grains of radius πR/12; 55.7 : 16.5=3.38). To the terrestrial wavelength 10000 km (πR/2) corresponds frequency 0.03 khz, to the venusian 6000 km (πR/3) 0.07 khz. Venusian oscillations thus 2.33 times more frequent. If a degassing difference of two planets is the square (degassing goes through surface) of the production of differences in granulation and oscillation frequencies, then Venus is 62 times more outgassed [Dv /De = (3.38 x 2.33)2 =62.1]. Actually the venusian atmosphere is 90 times more massive than the terrestrial one. Comparing Mars (1/10th of the Earth's mass) and Earth by the same method we get 920 times less massive martian atmosphere (actually only about 200 times). The discrepancy probably is due to large amounts of volatiles in soils and crust (ice, aqueous salts, zeolites) exchanging them with atmosphere under changing conditions. On contrary, Mercury is completely "shaken out", 1 dry, its would-be massive atmosphere is completely eliminated by solar wind. The smaller volatile rich Titan with high orbital frequency has an important atmosphere -probably only remnants of what was totally outgassed during eons. All Titan's dark plains (frozen methane?) are intensively warped by cross-cutting ridge-groove systems -a consequence of an important subsidence, loosing radius. So, there is an inverse relation between atmospheric masses and a volatile stock in planets. Dry Venus has a massive atmosphere, wet Mars has a weak one. Earth is in the middle: rather wet interior and an important atmosphere. Most outgassed Mercury with distinct traces of earlier contraction (escarps or lobate ledges), alas, has lost its gaseous envelope. Asteroids , next to Mars, as show carboneceous chondrites are rich in volatiles. Sharing an angular momentum between a solid body and a massive gaseous envelope enforces this body rotate slower (Venus, Mercury). This observation could perhaps explain one enigmatic situation: the larger asteroids rotate faster than smaller ones. A reason: the former less wasted their "original" momentum not spending it with loosing volatiles than the latter, more degassed. References: [1] Kochemaov G.G. (2003) Tectonically and chemically dichotomic Mars is the least outgassed of terrestrial planets // Vernadsky-Brown microsymp. 38, Oct. 27-29, 2003, Vernadsky Inst., Moscow, Russia, Abstr.,(CD-ROM). 2

Treatment of HMX-production wastewater in an aerobic granular reactor.

PubMed

Zhang, Jin-Hua; Wang, Min-Hui; Zhu, Xiao-Meng

2013-04-01

Aerobic granules were applied to the treatment of HMX-production wastewater using a gradual domestication method in a SBR. During the process, the granules showed a good settling ability, a high biomass retention rate, and high biological activity. After 40 days of stable operation, aerobic granular sludge performed very effectively in the removal of carbon and nitrogen compounds from HMX-production wastewater. Organic matter removal rates up to 97.57% and nitrogen removal efficiencies up to 80% were achieved during the process. Researchers conclude that using aerobic granules to treat explosive wastewater has good prospects for success.

Granulation tissue formation at the bronchial stump is reduced after stapler closure in comparison to suture closure in dogs.

PubMed

Izumi, Yotaro; Kawamura, Masafumi; Gika, Masatoshi; Nomori, Hiroaki

2010-03-01

The aim of this study was to compare the morphology of the bronchial stump after lobectomy between mechanical stapler closure and manual suture closure. The effect of fibrin glue application on each method of closure was also observed. Right upper lobectomy was performed in beagles (n=31) using staplers (ST group) or sutures (SU group). In a separate experiment, fibrin glue was sprayed onto the stump after each respective method of closure. After one week, the stump region was examined macroscopically, and also by histology. chi(2)-Test and Mann-Whitney test were used for comparative analysis. The incidence of adhesion formation between the surrounding tissues was significantly reduced in the ST group in comparison to the SU group (22 vs. 80%, P=0.04). The thickness of granulation tissue over the stump was significantly reduced in the ST group in comparison to the SU group (0.8+/-0.2 vs. 2.5+/-0.3 mm, P<0.0001). Vessel density in the granulation tissue was also significantly reduced in the ST group in comparison to the SU group (6+/-2 vs. 16+/-2, P=0.003). Fibrin glue application after stapler closure significantly increased the incidence of adhesion formation, granulation tissue thickness, and vessel density in the granulation tissue over the stump.

Granular support vector machines with association rules mining for protein homology prediction.

PubMed

Tang, Yuchun; Jin, Bo; Zhang, Yan-Qing

2005-01-01

Protein homology prediction between protein sequences is one of critical problems in computational biology. Such a complex classification problem is common in medical or biological information processing applications. How to build a model with superior generalization capability from training samples is an essential issue for mining knowledge to accurately predict/classify unseen new samples and to effectively support human experts to make correct decisions. A new learning model called granular support vector machines (GSVM) is proposed based on our previous work. GSVM systematically and formally combines the principles from statistical learning theory and granular computing theory and thus provides an interesting new mechanism to address complex classification problems. It works by building a sequence of information granules and then building support vector machines (SVM) in some of these information granules on demand. A good granulation method to find suitable granules is crucial for modeling a GSVM with good performance. In this paper, we also propose an association rules-based granulation method. For the granules induced by association rules with high enough confidence and significant support, we leave them as they are because of their high "purity" and significant effect on simplifying the classification task. For every other granule, a SVM is modeled to discriminate the corresponding data. In this way, a complex classification problem is divided into multiple smaller problems so that the learning task is simplified. The proposed algorithm, here named GSVM-AR, is compared with SVM by KDDCUP04 protein homology prediction data. The experimental results show that finding the splitting hyperplane is not a trivial task (we should be careful to select the association rules to avoid overfitting) and GSVM-AR does show significant improvement compared to building one single SVM in the whole feature space. Another advantage is that the utility of GSVM-AR is very good because it is easy to be implemented. More importantly and more interestingly, GSVM provides a new mechanism to address complex classification problems.

Design, development, and optimization of polymeric based-colonic drug delivery system of naproxen.

PubMed

Sharma, Pooja; Chawla, Anuj; Pawar, Pravin

2013-01-01

The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting.

Design, Development, and Optimization of Polymeric Based-Colonic Drug Delivery System of Naproxen

PubMed Central

Sharma, Pooja; Chawla, Anuj; Pawar, Pravin

2013-01-01

The aim of present investigation deals with the development of time-dependent and pH sensitive press-coated tablets for colon specific drug delivery of naproxen. The core tablets were prepared by wet granulation method then press coated with hydroxypropyl cellulose (HPC) or Eudragit RSPO : RLPO mixture and further coated with Eudragit S-100 by dip immerse method. The in vitro drug release study was conducted in different dissolution media such as pH 1.2, 6.8, and 7.4 with or without rat caecal content to simulate GIT conditions. Surface morphology and cross-sectional view of the tablets were visualized by scanning electron microscopy (SEM). All prepared batches were in compliance with the pharmacopoeial standards. The tablets which are compression coated with HPC followed by Eudragit S-100 coated showed highest in vitro drug release of 98.10% in presence of rat caecal content. The SEM of tablets suggested that the number of pores got increased in pH 7.4 medium followed by dissolution of coating layer. The tablets coat erosion study suggested that the lag time depends upon the coating concentrations of polymers. A time-dependent hydrophilic polymer and pH sensitive polymer based press-coated tablets of naproxen were promising delivery for colon targeting. PMID:24198725

Expression and subcellular localization of the Qa-SNARE syntaxin17 in human eosinophils

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carmo, Lívia A.S.; Dias, Felipe F.; Malta, Kássia K.

Background: SNARE members mediate membrane fusion during intracellular trafficking underlying innate and adaptive immune responses by different cells. However, little is known about the expression and function of these proteins in human eosinophils, cells involved in allergic, inflammatory and immunoregulatory responses. Here, we investigate the expression and distribution of the Qa-SNARE syntaxin17 (STX17) within human eosinophils isolated from the peripheral blood. Methods: Flow cytometry and a pre-embedding immunonanogold electron microscopy (EM) technique that combines optimal epitope preservation and secondary Fab-fragments of antibodies linked to 1.4 nm gold particles for optimal access to microdomains, were used to investigate STX17. Results: STX17more » was detected within unstimulated eosinophils. Immunogold EM revealed STX17 on secretory granules and on granule-derived vesiculotubular transport carriers (Eosinophil Sombrero Vesicles-EoSVs). Quantitative EM analyses showed that 77.7% of the granules were positive for STX17 with a mean±SEM of 3.9±0.2 gold particles/granule. Labeling was present on both granule outer membranes and matrices while EoSVs showed clear membrane-associated labeling. STX17 was also present in secretory granules in eosinophils stimulated with the cytokine tumor necrosis factor alpha (TNF-α) or the CC-chemokine ligand 11 CCL11 (eotaxin-1), stimuli that induce eosinophil degranulation. The number of secretory granules labeled for STX17 was significantly higher in CCL11 compared with the unstimulated group. The level of cell labeling did not change when unstimulated cells were compared with TNF-α-stimulated eosinophils. Conclusions: The present study clearly shows by immunanonogold EM that STX17 is localized in eosinophil secretory granules and transport vesicles and might be involved in the transport of granule-derived cargos. - Highlights: • First demonstration of the Qa-SNARE syntaxin-17 (STX17) in human eosinophils. • High resolution immunogold EM shows STX17 in granules and tubular vesicles. • Unstimulated, TNF-α or CCL11-stimulated eosinophils express STX17. • Our findings suggest a role for STX17 in the transport of granule-derived cargos.« less

Understanding and optimizing the dual excipient functionality of sodium lauryl sulfate in tablet formulation of poorly water soluble drug: wetting and lubrication.

PubMed

Aljaberi, Ahmad; Chatterji, Ashish; Dong, Zedong; Shah, Navnit H; Malick, Waseem; Singhal, Dharmendra; Sandhu, Harpreet K

2013-01-01

To evaluate and optimize sodium lauryl sulfate (SLS) and magnesium stearate (Mg.St) levels, with respect to dissolution and compaction, in a high dose, poorly soluble drug tablet formulation. A model poorly soluble drug was formulated using high shear aqueous granulation. A D-optimal design was used to evaluate and model the effect of granulation conditions, size of milling screen, SLS and Mg.St levels on tablet compaction and ejection. The compaction profiles were generated using a Presster(©) compaction simulator. Dissolution of the kernels was performed using a USP dissolution apparatus II and intrinsic dissolution was determined using a stationary disk system. Unlike kernels dissolution which failed to discriminate between tablets prepared with various SLS contents, the intrinsic dissolution rate showed that a SLS level of 0.57% was sufficient to achieve the required release profile while having minimal effect on compaction. The formulation factors that affect tablet compaction and ejection were identified and satisfactorily modeled. The design space of best factor setting to achieve optimal compaction and ejection properties was successfully constructed by RSM analysis. A systematic study design helped identify the critical factors and provided means to optimize the functionality of key excipient to design robust drug product.

Conformational study of the proline rich peptide from bovine neurohypophysis secretory granules

NASA Astrophysics Data System (ADS)

Alieva, Irada; Velieva, Lala; Aliev, Dshavanchir; Gojayev, Niftali; Demukhamedova, Svetlana

2004-01-01

The spatial organization and conformational properties of the Proline Rich Peptide (PRP) from bovine neurohypophysis secretory granules have been established by the methods of molecular mechanics and molecular dynamics simulations in water solution. Conformational studies showed the peptide with limited conformational flexibility. Two β-type III turns are observed in PRP spatial organization.

A simple and rapid method for preparing the whole section of starchy seed to investigate the morphology and distribution of starch in different regions of seed.

PubMed

Zhao, Lingxiao; Pan, Ting; Guo, Dongwei; Wei, Cunxu

2018-01-01

Storage starch in starchy seed influences the seed weight and texture, and determines its applications in food and nonfood industries. Starch granules from different plant sources have significantly different shapes and sizes, and even more the difference exists in the different regions of the same tissue. Therefore, it is very important to in situ investigate the morphology and distribution of starch in the whole seed. However, a simple and rapid method is deficient to prepare the whole section of starchy seed for investigating the morphology and distribution of starch in the whole seeds for a large number of samples. A simple and rapid method was established to prepare the whole section of starchy seed, especially for floury seed, in this study. The whole seeds of translucent and chalky rice, vitreous and floury maize, and normal barley and wheat were sectioned successfully using the newly established method. The iodine-stained section clearly exhibited the shapes and size of starch granules in different regions of seed. The starch granules with different morphologies and iodine-staining colors existed regionally in the seeds of high-amylose rice and maize. The sections of lotus and kidney bean seeds also showed the feasibility of this method for starchy non-cereal seeds. The simple and rapid method was proven effective for preparing the whole sections of starchy seeds. The whole section of seed could be used to investigate the morphology and distribution of starch granules in different regions of the whole seed. The method was especially suitable for large sample numbers to investigate the starch morphology in short time.

Concurrent validation and reliability of digital image analysis of granulation tissue color for clinical pressure ulcers.

PubMed

Iizaka, Shinji; Sugama, Junko; Nakagami, Gojiro; Kaitani, Toshiko; Naito, Ayumi; Koyanagi, Hiroe; Matsuo, Junko; Kadono, Takafumi; Konya, Chizuko; Sanada, Hiromi

2011-01-01

Granulation tissue color is one indicator for pressure ulcer (PU) assessment. However, it entails a subjective evaluation only, and quantitative methods have not been established. We developed color indicators from digital image analysis and investigated their concurrent validity and reliability for clinical PUs. A cross-sectional study was conducted on 47 patients with 55 full-thickness PUs. After color calibration, a wound photograph was converted into three images representing red color: erythema index (EI), modified erythema index with additional color calibration (granulation red index [GRI]), and , which represents the artificially created red-green axis of L(*) a(*) b(*) color space. The mean intensity of the granulation tissue region and the percentage of pixels exceeding the optimal cutoff intensity (% intensity) were calculated. Mean GRI (ρ=0.39, p=0.007) and (ρ=0.55, p<0.001), as well as their % intensity indicators, showed positive correlations with a(*) measured by tristimulus colorimeter, but erythema index did not. They were correlated with hydroxyproline concentration in wound fluid, healthy granulation tissue area, and blood hemoglobin level. Intra- and interrater reliability of the indicator calculation using both GRI and had an intraclass correlation coefficient >0.9. GRI and from digital image analysis can quantitatively evaluate granulation tissue color of clinical PUs. © 2011 by the Wound Healing Society.

Microstructure and Mechanical Properties of Ti-6Al-4V Fabricated by Selective Laser Melting of Powder Produced by Granulation-Sintering-Deoxygenation Method

NASA Astrophysics Data System (ADS)

Sun, Pei; Fang, Z. Zak; Zhang, Ying; Xia, Yang

2017-12-01

Commercial spherical Ti powders for additive manufacturing applications are produced today by melt-atomization methods at relatively high costs. A meltless production method, called granulation-sintering-deoxygenation (GSD), was developed recently to produce spherical Ti alloy powder at a significantly reduced cost. In this new process, fine hydrogenated Ti particles are agglomerated to form spherical granules, which are then sintered to dense spherical particles. After sintering, the solid fully dense spherical Ti alloy particles are deoxygenated using novel low-temperature deoxygenation processes with either Mg or Ca. This technical communication presents results of 3D printing using GSD powder and the selective laser melting (SLM) technique. The results showed that tensile properties of parts fabricated from spherical GSD Ti-6Al-4V powder by SLM are comparable with typical mill-annealed Ti-6Al-4V. The characteristics of 3D printed Ti-6Al-4V from GSD powder are also compared with that of commercial materials.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules IV.(1)) Evaluation of the controlled release properties for in vivo and in vitro release systems.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2007-11-01

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the release properties. The dissolution test is a very important and useful method for understanding and predicting drug-release properties. It was readily confirmed in the previous paper that the release process could be assessed quantitatively by a combination of the square-root time law and cube-root law equations for ethylcellulose (EC) matrix granules of phenylpropanolamine hydrochloride (PPA). In this paper EC layered granules were used in addition to EC matrix. The relationship between release property and the concentration of PPA in plasma after administration using beagle dogs were examined. Then it was confirmed that the correlativity for EC layered granules and EC matrix were similar each other. Therefore, it was considered that the dissolution test is useful for prediction of changes in concentration of PPA in the blood with time. And it was suggested that EC layered granules were suitable as a controlled release system as well as EC matrix.

Hydroxyapatite and bioactive glass surfaces for fiber reinforced composite implants via surface ablation by Excimer laser.

PubMed

Kulkova, Julia; Moritz, Niko; Huhtinen, Hannu; Mattila, Riina; Donati, Ivan; Marsich, Eleonora; Paoletti, Sergio; Vallittu, Pekka K

2017-11-01

In skeletal reconstructions, composites, such as bisphenol-A-glycidyldimethacrylate resin reinforced with glass fibers, are potentially useful alternatives to metallic implants. Recently, we reported a novel method to prepare bioactive surfaces for these composites. Surface etching by Excimer laser was used to expose bioactive glass granules embedded in the resin. The purpose of this study was to analyze two types of bioactive surfaces created by this technique. The surfaces contained bioactive glass and hydroxyapatite granules. The selected processing parameters were adequate for the creation of the surfaces. However, the use of porous hydroxyapatite prevented the complete exposure the granules. In cell culture, for bioactive glass coatings, the pattern of proliferation of MG63 cells was comparable to that in the positive control group (Ti6Al4V) while inferior cell proliferation was observed on the surfaces containing hydroxyapatite granules. Scanning electron microscopy revealed osteointegration of implants with both types of surfaces. The technique is suitable for the exposure of solid bioactive glass granules. However, the long-term performance of the surfaces needs further assessment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Bioequivalence of the 4-mg Oral Granules and Chewable Tablet Formulations of Montelukast.

PubMed

Knorr, Barbara; Hartford, Alan; Li, Xiujiang Susie; Yang, Amy Yifan; Noonan, Gertrude; Migoya, Elizabeth

2010-06-01

PURPOSE: The primary objective of the studies was to demonstrate bioequivalence between the oral granules formulation and chewable tablet of montelukast in the fasted state. Effect of food on the pharmacokinetics of the oral granules was also evaluated. METHODS: The Formulation Biocomparison Study (Study 1) and the Final Market Image Study (Study 2) each used an open-label, randomized, 3-period crossover design where healthy adult subjects (N = 24 and 30, respectively) received montelukast as a single 4-mg dose of the oral granules formulation and a 4-mg chewable tablet fasted, and a single 4-mg dose of the oral granules formulation with food (on 2 teaspoons of applesauce [Study 1] or after consumption of a high-fat breakfast [Study 2]). The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) for geometric mean ratios (GMRs) (oral granules/chewable tablet) for the AUC(0-infinity) and C(max) of montelukast were within the prespecified comparability bounds of (0.80, 1.25). For the food-effect assessment in Study 1, comparability bounds were prespecified as (0.50, 2.00) only for the 90% CI of the GMR (oral granules fed/oral granules fasted) for the AUC(0-infinity) of montelukast; the 90% CI of the GMR for the C(max) of montelukast, however, also was computed. In Study 2, 90% CIs of the GMRs (oral granules fed/oral granules fasted) for the AUC(0-infinity) and C(max) of montelukast were computed; comparability bounds were not prespecified. RESULTS: Comparing the exposure of the formulations, the 90% CIs of the GMRs for AUC(0-infinity) and C(max) were within the prespecified bound of (0.80, 1.25). For AUC(0-infinity), the GMRs (90% CI) for Study 1 and Study 2 were 1.01 (0.92, 1.11) and 0.95 (0.91, 0.99), respectively. For C(max), respective values were 0.99 (0.86, 1.13) and 0.92 (0.84, 1.01). When the oral granules formulation was administered with food, 90% CIs of the GMRs for both AUC(0-infinity) and C(max) in both studies were contained within the interval of (0.50, 2.00). CONCLUSIONS: The 4-mg oral granules and 4-mg chewable tablet formulations of montelukast administered in the fasted state are bioequivalent. Single 4-mg doses of the oral granules formulation and the chewable tablet of montelukast are generally well tolerated.

Bioequivalence of the 4-mg Oral Granules and Chewable Tablet Formulations of Montelukast

PubMed Central

Knorr, Barbara; Hartford, Alan; Li, Xiujiang (Susie); Yang, Amy Yifan; Noonan, Gertrude; Migoya, Elizabeth

2010-01-01

Purpose The primary objective of the studies was to demonstrate bioequivalence between the oral granules formulation and chewable tablet of montelukast in the fasted state. Effect of food on the pharmacokinetics of the oral granules was also evaluated. Methods The Formulation Biocomparison Study (Study 1) and the Final Market Image Study (Study 2) each used an open-label, randomized, 3-period crossover design where healthy adult subjects (N = 24 and 30, respectively) received montelukast as a single 4-mg dose of the oral granules formulation and a 4-mg chewable tablet fasted, and a single 4-mg dose of the oral granules formulation with food (on 2 teaspoons of applesauce [Study 1] or after consumption of a high-fat breakfast [Study 2]). The formulations were to be considered bioequivalent if the 90% confidence intervals (CIs) for geometric mean ratios (GMRs) (oral granules/chewable tablet) for the AUC0-∞ and Cmax of montelukast were within the prespecified comparability bounds of (0.80, 1.25). For the food-effect assessment in Study 1, comparability bounds were prespecified as (0.50, 2.00) only for the 90% CI of the GMR (oral granules fed/oral granules fasted) for the AUC0-∞ of montelukast; the 90% CI of the GMR for the Cmax of montelukast, however, also was computed. In Study 2, 90% CIs of the GMRs (oral granules fed/oral granules fasted) for the AUC0-∞ and Cmax of montelukast were computed; comparability bounds were not prespecified. Results Comparing the exposure of the formulations, the 90% CIs of the GMRs for AUC0-∞ and Cmax were within the prespecified bound of (0.80, 1.25). For AUC0-∞, the GMRs (90% CI) for Study 1 and Study 2 were 1.01 (0.92, 1.11) and 0.95 (0.91, 0.99), respectively. For Cmax, respective values were 0.99 (0.86, 1.13) and 0.92 (0.84, 1.01). When the oral granules formulation was administered with food, 90% CIs of the GMRs for both AUC0-∞ and Cmax in both studies were contained within the interval of (0.50, 2.00). Conclusions The 4-mg oral granules and 4-mg chewable tablet formulations of montelukast administered in the fasted state are bioequivalent. Single 4-mg doses of the oral granules formulation and the chewable tablet of montelukast are generally well tolerated. PMID:20686624

Changes in biochemical processes in cerebellar granule cells of mice exposed to methylmercury.

PubMed

Bellum, Sairam; Bawa, Bhupinder; Thuett, Kerry A; Stoica, Gheorghe; Abbott, Louise C

2007-01-01

At postnatal day 34, male and female C57BL/6J mice were exposed orally once a day to a total of five doses totaling 1.0 or 5.0 mg/kg of methylmercuric chloride or sterile deionized water in moistened rodent chow. Eleven days after the last dose cerebellar granule cells were acutely isolated to measure reactive oxygen species (ROS) levels and mitochondrial membrane potential using CM-H(2)DCFDA and TMRM dyes, respectively. For visualizing intracellular calcium ion distribution using transmission electron microscopy, mice were perfused 11 days after the last dose of methylmercury (MeHg) using the oxalate-pyroantimonate method. Cytosolic and mitochondrial protein fractions from acutely isolated granule cells were analyzed for cytochrome c content using Western blot analysis. Histochemistry (Fluoro-Jade dye) and immunohistochemistry (activated caspase 3) was performed on frozen serial cerebellar sections to label granule cell death and activation of caspase 3, respectively. Granule cells isolated from MeHg-treated mice showed elevated ROS levels and decreased mitochondrial membrane potential when compared to granule cells from control mice. Electron photomicrographs of MeHg-treated granule cells showed altered intracellular calcium ion homeostasis ([Ca(2+)](i)) when compared to control granule cells. However, in spite of these subcellular changes and moderate relocalization of cytochrome c into the cytosol, the concentrations of MeHg used in this study did not produce significant neuronal cell death/apoptosis at the time point examined, as evidenced by Fluoro-Jade and activated caspase 3 immunostaining, respectively. These results demonstrate that short-term in vivo exposure to total doses of 1.0 and 5.0 mg/kg MeHg through the most common exposure route (oral) can result in significant subcellular changes that are not accompanied by overt neuronal cell death.

Large-scale horizontal flows from SOUP observations of solar granulation

NASA Technical Reports Server (NTRS)

November, L. J.; Simon, G. W.; Tarbell, T. D.; Title, A. M.; Ferguson, S. H.

1987-01-01

Using high resolution time sequence photographs of solar granulation from the SOUP experiment on Spacelab 2, large scale horizontal flows were observed in the solar surface. The measurement method is based upon a local spatial cross correlation analysis. The horizontal motions have amplitudes in the range 300 to 1000 m/s. Radial outflow of granulation from a sunspot penumbra into surrounding photosphere is a striking new discovery. Both the supergranulation pattern and cellular structures having the scale of mesogranulation are seen. The vertical flows that are inferred by continuity of mass from these observed horizontal flows have larger upflow amplitudes in cell centers than downflow amplitudes at cell boundaries.

[Optimization of one-step pelletization technology of Biqiu granules by Plackett-Burman design and Box-Behnken response surface methodology].

PubMed

Zhang, Yan-jun; Liu, Li-li; Hu, Jun-hua; Wu, Yun; Chao, En-xiang; Xiao, Wei

2015-11-01

First with the qualified rate of granules as the evaluation index, significant influencing factors were firstly screened by Plackett-Burman design. Then, with the qualified rate and moisture content as the evaluation indexes, significant factors that affect one-step pelletization technology were further optimized by Box-Behnken design; experimental data were imitated by multiple regression and second-order polynomial equation; and response surface method was used for predictive analysis of optimal technology. The best conditions were as follows: inlet air temperature of 85 degrees C, sample introduction speed of 33 r x min(-1), density of concrete 1. 10. One-step pelletization technology of Biqiu granules by Plackett-Burman design and Box-Behnken response surface methodology was stable and feasible with good predictability, which provided reliable basis for the industrialized production of Biqiu granules.

Development and evaluation of Ca(+ 2) ion cross-linked carboxymethyl xanthan gum tablet prepared by wet granulation technique.

PubMed

Maity, Siddhartha; Sa, Biswanath

2014-08-01

The objective of this work was to study the release behavior of prednisolone from calcium-cross-linked carboxymethyl xanthan gum (CMXG) tablets in dissolution medium having different pH values prevailing in the gastrointestinal lumen. Xanthan gum (XG) was derivatized to CMXG which was then cross-linked in situ with Ca(+2) ion during wet massing step of tablet preparation. Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry studies did not show any drug-polymer interaction although the drug underwent solid-state transformation during compression as evident from X-ray diffraction analysis. In vitro release study demonstrated that increase in the amount of Ca(+2) ion decreased the drug release, and beyond a certain amount, the drug release increased. While increase in both drug load and tablet crushing strength decreased the drug release, increase in exposure time in acid solution of pH 1.2 increased the overall release of the drug. The mechanism of drug release was non-Fickian/anomalous. The results indicated that variation in the amount of Ca(+2) ion can modulate the drug release from CMXG matrix tablets as needed.

Beta-tricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo.

PubMed

Gao, Peng; Zhang, Haoqiang; Liu, Yun; Fan, Bo; Li, Xiaokang; Xiao, Xin; Lan, Pingheng; Li, Minghui; Geng, Lei; Liu, Dong; Yuan, Yulin; Lian, Qin; Lu, Jianxi; Guo, Zheng; Wang, Zhen

2016-03-22

The drawbacks of traditional bone-defect treatments have prompted the exploration of bone tissue engineering. This study aimed to explore suitable β-tricalcium phosphate (β-TCP) granules for bone regeneration and identify an efficient method to establish β-TCP-based osteo-regenerators. β-TCP granules with diameters of 1 mm and 1-2.5 mm were evaluated in vitro. The β-TCP granules with superior osteogenic properties were used to establish in vivo bioreactors, referred to as osteo-regenerators, which were fabricated using two different methods. Improved proliferation of bone mesenchymal stem cells (BMSCs), glucose consumption and ALP activity were observed for 1-2.5 mm β-TCP compared with 1-mm granules (P < 0.05). In addition, BMSCs incubated with 1-2.5 mm β-TCP expressed significantly higher levels of the genes for runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 and the osteogenesis-related proteins alkaline phosphatase, collagen type-1 and runt-related transcription factor-2 compared with BMSCs incubated with 1 mm β-TCP (P < 0.05). Fluorochrome labelling, micro-computed tomography and histological staining analyses indicated that the osteo-regenerator with two holes perforating the femur promoted significantly greater bone regeneration compared with the osteo-regenerator with a periosteum incision (P < 0.05). This study provides an alternative to biofunctionalized bioreactors that exhibits improved osteogenesis.

Inhibitory effect of mitomycin C on proliferation of primary cultured fibroblasts from human airway granulation tissues.

PubMed

Chen, Nan; Zhang, Jie; Xu, Min; Wang, Yu Ling; Pei, Ying Hua

2013-01-01

Airway granulation tissue and scar formation pose a challenge because of the high incidence of recurrence after treatment. As an emerging treatment modality, topical application of mitomycin C has potential value in delaying the recurrence of airway obstruction. Several animal and clinical studies have already proven its feasibility and efficacy. However, the ideal dosage has still not been determined. To establish a novel method for culturing primary fibroblasts isolated from human airway granulation tissue, and to investigate the dose-effect of mitomycin C on the fibroblast proliferation in vitro, so as to provide an experimental reference for clinical practitioners. Granulation tissues were collected during the routine bronchoscopy at our department. The primary fibroblasts were obtained by culturing the explanted tissues. The cells were treated with different concentrations of mitomycin C (0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml) for 5 min followed by additional 48-hour culture before an MTT assay was performed to measure cell viability. MTT assay showed that mitomycin C reduced cell viability at all tested concentrations. The inhibitory ratios were 10.26, 26.77, 32.88, 64.91 and 80.45% for cells treated with mitomycin C at 0.1, 0.2, 0.4, 0.8 and 1.6 mg/ml, respectively. Explant culture is a reliable method for culturing primary fibroblasts from human airway granulation tissue, and mitomycin C can inhibit proliferation of the fibroblasts in vitro. Copyright © 2013 S. Karger AG, Basel.

Beta-tricalcium phosphate granules improve osteogenesis in vitro and establish innovative osteo-regenerators for bone tissue engineering in vivo

PubMed Central

Gao, Peng; Zhang, Haoqiang; Liu, Yun; Fan, Bo; Li, Xiaokang; Xiao, Xin; Lan, Pingheng; Li, Minghui; Geng, Lei; Liu, Dong; Yuan, Yulin; Lian, Qin; Lu, Jianxi; Guo, Zheng; Wang, Zhen

2016-01-01

The drawbacks of traditional bone-defect treatments have prompted the exploration of bone tissue engineering. This study aimed to explore suitable β-tricalcium phosphate (β-TCP) granules for bone regeneration and identify an efficient method to establish β-TCP-based osteo-regenerators. β-TCP granules with diameters of 1 mm and 1–2.5 mm were evaluated in vitro. The β-TCP granules with superior osteogenic properties were used to establish in vivo bioreactors, referred to as osteo-regenerators, which were fabricated using two different methods. Improved proliferation of bone mesenchymal stem cells (BMSCs), glucose consumption and ALP activity were observed for 1–2.5 mm β-TCP compared with 1-mm granules (P < 0.05). In addition, BMSCs incubated with 1–2.5 mm β-TCP expressed significantly higher levels of the genes for runt-related transcription factor-2, alkaline phosphatase, osteocalcin, osteopontin, and collagen type-1 and the osteogenesis-related proteins alkaline phosphatase, collagen type-1 and runt-related transcription factor-2 compared with BMSCs incubated with 1 mm β-TCP (P < 0.05). Fluorochrome labelling, micro-computed tomography and histological staining analyses indicated that the osteo-regenerator with two holes perforating the femur promoted significantly greater bone regeneration compared with the osteo-regenerator with a periosteum incision (P < 0.05). This study provides an alternative to biofunctionalized bioreactors that exhibits improved osteogenesis. PMID:27000963

Taste-masked and affordable donepezil hydrochloride orally disintegrating tablet as promising solution for non-compliance in Alzheimer's disease patients.

PubMed

Liew, Kai Bin; Tan, Yvonne Tze Fung; Peh, Kok Khiang

2015-04-01

Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly. The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient. The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®. Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug. The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.

Linking local circuit inhibition to olfactory behavior: a critical role for granule cells in olfactory discrimination.

PubMed

Strowbridge, Ben W

2010-02-11

In this issue of Neuron, Abraham et al. report a direct connection between inhibitory function and olfactory behavior. Using molecular methods to alter glutamate receptor subunit composition in olfactory bulb granule cells, the authors found a selective modulation in the time required for difficult, but not simple, olfactory discrimination tasks. Copyright 2010 Elsevier Inc. All rights reserved.

Chemical fingerprint of Ganmaoling granule by double-wavelength ultra high performance liquid chromatography and ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

PubMed

Lou, Qiong; Ye, Xiaolan; Zhou, Yingyi; Li, Hua; Song, Fenyun

2015-06-01

A method incorporating double-wavelength ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was developed for the investigation of the chemical fingerprint of Ganmaoling granule. The chromatographic separations were performed on an ACQUITY UPLC HSS C18 column (2.1 × 50 mm, 1.8 μm) at 30°C using gradient elution with water/formic acid (1%) and acetonitrile at a flow rate of 0.4 mL/min. A total of 11 chemical constituents of Ganmaoling granule were identified from their molecular weight, UV spectra, tandem mass spectrometry data, and retention behavior by comparing the results with those of the reference standards or literature. And 25 peaks were selected as the common peaks for fingerprint analysis to evaluate the similarities among 25 batches of Ganmaoling granule. The results of principal component analysis and orthogonal projection to latent structures discriminant analysis showed that the important chemical markers that could distinguish the different batches were revealed as 4,5-di-O-caffeoylquinic acid, 3,5-di-O-caffeoylquinic acid, and 4-O-caffeoylquinic acid. This is the first report of the ultra high performance liquid chromatography chemical fingerprint and component identification of Ganmaoling granule, which could lay a foundation for further studies of Ganmaoling granule. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Secretory granule formation and membrane recycling by the trans-Golgi network in adipokinetic cells of Locusta migratoria in relation to flight and rest.

PubMed

Diederen, J H; Vullings, H G

1995-03-01

The influence of flight activity on the formation of secretory granules and the concomitant membrane recycling by the trans-Golgi network in the peptidergic neurosecretory adipokinetic cells of Locusta migratoria was investigated by means of ultrastructural morphometric methods. The patterns of labelling of the trans-Golgi network by the exogenous adsorptive endocytotic tracer wheat-germ agglutinin-conjugated horse-radish peroxidase and by the endogenous marker enzyme acid phosphatase were used as parameters and were measured by an automatic image analysis system. The results show that endocytosed fragments of plasma membrane with bound peroxidase label were transported to the trans-Golgi network and used to build new secretory granules. The amounts of peroxidase and especially of acid phosphatase within the trans-Golgi network showed a strong tendency to be smaller in flight-stimulated cells than in non-stimulated cells. The amounts of acid phosphatase in the immature secretory granules originating from the trans-Golgi network were significantly smaller in stimulated cells. The number of immature secretory granules positive for acid phosphatase tended to be higher in stimulated cells. Thus, flight stimulation of adipokinetic cells for 1 h influences the functioning of the trans-Golgi network; this most probably results in a slight enhancement of the production of secretory granules by the trans-Golgi network.

MODster: Namespaces and Redirection for Earth Science Data

NASA Astrophysics Data System (ADS)

Frew, J.; Metzger, D.; Slaughter, P.

2005-12-01

MODster is a distributed, decentralized inventory server for Earth science data granules (standard units of data content and structure.) MODster connects data granule users (people who know which specific granule they want, but who don't know who has it or how to get it) with data granule providers (people or institutions that keep granules accessible online.) * If you're a provider, you can tell MODster which granules you have and where they live (i.e., their URLs.) * If you're a user, you can ask MODster for a granule, and it will transparently redirect your request to whomever has it. The key to making this work is a standard granule namespace. A granule namespace is a naming convention that associates particular names with particular granules, regardless of where those granules live. Different Earth science data products have their own granule namespaces. For example, in the MODIS granule namespace, the granule name "MOD43A2.A1998365.h5.v8.001.1999001090020.hdf" always refers to version 1 of the 5th horizontal and 8th vertical tile of the Level 3 16-day Bi-directional Reflectance Distribution Function product, acquired by the MODIS Terra sensor on 31 December 1998 and generated on 01 January 1999 at 9:00:20 AM. A MODster URL is simply a standard way of referring to a data product namespace and one of its granules. MODster URLs have the general form "http://server/namespace/granule" where "granule" is a granule name that conforms to a granule namespace, "namespace" is a MODster namespace, which is the name of a granule namespace whose conventions are known to MODster, and "server" is a MODster server, which is an HTTP server that can redirect namespace/granule requests to granule providers. A MODster URL with no granule component gets a description of the MODster namespace, its authority (the persons or institutions responsible for documenting and maintaining the naming convention), and also any services for that MODster namespace that the MODster server supports. Our current MODster implementation allows granule providers to explicitly register their granules, and can also crawl provider sites looking for granules whose names match specific rules or regular expressions.

[Localization of substance P- and FMRFamide-like immunoreactivity in the atrium of the snail Achatina fulica].

PubMed

Shabel'nikov, S V; Bystrova, O A; Martynova, M G

2008-01-01

By immunohistochemical and immunocytochemical methods localization of Substanse P (SP) and FMRFamide in the atrium of the snail Achatina fulica was investigated. Nerve fibers innervating the snail atrium contact tightly with the granular cells (GC) situated between muscle and endocardial cells, forming neuroendocrine units. Both neuromediators were found in the cells of the neuroendocrine units. By immunohistochemistry SP- and FMRFamide-immunoreactive material was revealed in the granules of the atrial GC. Elecrtonmicroscopical immunocytochemistry has confirmed the presence of SP- and FMRFamide-immunoreactive material in the granules of the GC and shown their presence in the neurosecretory granules of the nerve endings contacting both the atrial GC and cardiomyocytes.

Large-scale horizontal flows from SOUP observations of solar granulation

NASA Astrophysics Data System (ADS)

November, L. J.; Simon, G. W.; Tarbell, T. D.; Title, A. M.; Ferguson, S. H.

1987-09-01

Using high-resolution time-sequence photographs of solar granulation from the SOUP experiment on Spacelab 2 the authors observed large-scale horizontal flows in the solar surface. The measurement method is based upon a local spatial cross correlation analysis. The horizontal motions have amplitudes in the range 300 to 1000 m/s. Radial outflow of granulation from a sunspot penumbra into the surrounding photosphere is a striking new discovery. Both the supergranulation pattern and cellular structures having the scale of mesogranulation are seen. The vertical flows that are inferred by continuity of mass from these observed horizontal flows have larger upflow amplitudes in cell centers than downflow amplitudes at cell boundaries.

Decreasing effect and mechanism of moisture content of sludge biomass by granulation process.

PubMed

Zhao, Xia; Xu, Hao; Shen, Jimin; Yu, Bo; Wang, Xiaochun

2016-01-01

Disposal of a high volume of sludge significantly raises water treatment costs. A method for cultivating aerobic granules in a sequencing batch airlift bioreactor to significantly produce lower moisture content is described. Results indicate that optimization of settling time and control of the shear stresses acted on the granules. The diameter of the granule was within the range of 1.0-4.0 mm, and its sludge volume index was stabilized at 40-50 mL g(-1). Its specific gravity was increased by a factor of 0.0392, and specific oxygen uptake rate reached 60.126 mg h(-1) g(-1). Moreover, the percentage of its moisture content in the reactor ranged from 96.73% to 97.67%, and sludge volume was reduced to approximately 60%, greatly due to the presence of extracellular polymeric substances in the granules, as well as changes in their hydrophobic protein content. The removal rate of chemical oxygen demand and [Formula: see text] reaches up to 92.6% and 98%, respectively. The removal rates of total phosphorus is over 85%. Therefore, aerobic granular sludge process illustrates a good biological activity.

The Mealiness and Quality of Herbal Medicine: Licorice for Example.

PubMed

Liu, Xueying; Hou, Weilong; Dou, Deqiang

2017-01-01

The morphological identification is an effective and simple quality evaluation method in Chinese drugs, and the traits of mealiness and color were widely used in the commercial market of Chinese drugs. The objective of this study was to explore the correlation between mealiness of herbal drugs and its quality; licorice was selected as an example. The mealiness of licorice was graded by its weight; meanwhile, the content of glycyrrhizic acid and liquiritin was determined by high-performance liquid chromatography-diode-array detection method; the content of polysaccharides, soluble sugars, pectin, total starch, amylose, and amylopectin was measured by colorimetric method; and the number and diameter of starch granule were observed by microscope. The results showed that the mealiness of licorice which collected from wild and cultivated plants is positively correlated with the content of glycyrrhizic acid, liquiritin, the ratio of amylose to total starch, and the number of starch granules whose diameter was over 5 μm. However, the mealiness is negatively correlated with the total starch. Further, the formation mechanism of starch granule was discussed. It is for the first time to report the positive correlation between the mealiness and the starch granule size, the ratio of amylose to total starch, which can provide rationality for the quality evaluation using the character of mealiness in herbal medicine. It is a convenient method to justify the quality of herbal medicine. To explore the correlation between mealiness of herbal drugs and its quality, licorice was selected as an example. The result indicated that the effective constituent is correlated with mealiness of licorice. Abbreviations Used: TCM: Traditional Chinese Medicine.

Adsorption dynamics of methyl violet onto granulated mesoporous carbon: Facile synthesis and adsorption kinetics.

PubMed

Kim, Yohan; Bae, Jiyeol; Park, Hosik; Suh, Jeong-Kwon; You, Young-Woo; Choi, Heechul

2016-09-15

A new and facile one-step synthesis method for preparing granulated mesoporous carbon (GMC) with three-dimensional spherical mesoporous symmetry is prepared to remove large molecular weight organic compounds in aqueous phase. GMC is synthesized in a single step using as-synthesized mesoporous carbon particles and organic binders through a simple and economical synthesis approach involving a simultaneous calcination and carbonization process. Characterization results obtained from SEM, XRD, as well as surface and porosity analysis indicate that the synthesized GMC has similar physical properties to those of the powdered mesoporous carbon and maintains the Brunauer-Emmett-Teller (BET) surface area and pore volume because the new synthesis method prevents the collapse of the pores during the granulation process. Batch adsorption experiments revealed GMC showed a substantial adsorption capacity (202.8 mg/g) for the removal of methyl violet as a target large molecular contaminant in aqueous phase. The mechanisms and dynamics modeling of GMC adsorption were also fully examined, which revealed that surface diffusion was rate limiting step on adsorption process of GMC. Adsorption kinetics of GMC enables 3 times faster than that of granular activated carbon in terms of surface diffusion coefficient. This is the first study, to the best of our knowledge, to synthesize GMC as an adsorbent for water purification by using facile granulation method and to investigate the adsorption kinetics and characteristics of GMC. This study introduces a new and simple method for the synthesis of GMC and reveals its adsorption characteristics for large molecular compounds in a water treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

PHYSICAL PROPERTIES OF LARGE AND SMALL GRANULES IN SOLAR QUIET REGIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu Daren; Xie Zongxia; Hu Qinghua

The normal mode observations of seven quiet regions obtained by the Hinode spacecraft are analyzed to study the physical properties of granules. An artificial intelligence technique is introduced to automatically find the spatial distribution of granules in feature spaces. In this work, we investigate the dependence of granular continuum intensity, mean Doppler velocity, and magnetic fields on granular diameter. We recognized 71,538 granules by an automatic segmentation technique and then extracted five properties: diameter, continuum intensity, Doppler velocity, and longitudinal and transverse magnetic flux density to describe the granules. To automatically explore the intrinsic structures of the granules in themore » five-dimensional parameter space, the X-means clustering algorithm and one-rule classifier are introduced to define the rules for classifying the granules. It is found that diameter is a dominating parameter in classifying the granules and two families of granules are derived: small granules with diameters smaller than 1.''44, and large granules with diameters larger than 1.''44. Based on statistical analysis of the detected granules, the following results are derived: (1) the averages of diameter, continuum intensity, and Doppler velocity in the upward direction of large granules are larger than those of small granules; (2) the averages of absolute longitudinal, transverse, and unsigned flux density of large granules are smaller than those of small granules; (3) for small granules, the average of continuum intensity increases with their diameters, while the averages of Doppler velocity, transverse, absolute longitudinal, and unsigned magnetic flux density decrease with their diameters. However, the mean properties of large granules are stable; (4) the intensity distributions of all granules and small granules do not satisfy Gaussian distribution, while that of large granules almost agrees with normal distribution with a peak at 1.04 I{sub 0}.« less

Computational domain discretization in numerical analysis of flow within granular materials

NASA Astrophysics Data System (ADS)

Sosnowski, Marcin

2018-06-01

The discretization of computational domain is a crucial step in Computational Fluid Dynamics (CFD) because it influences not only the numerical stability of the analysed model but also the agreement of obtained results and real data. Modelling flow in packed beds of granular materials is a very challenging task in terms of discretization due to the existence of narrow spaces between spherical granules contacting tangentially in a single point. Standard approach to this issue results in a low quality mesh and unreliable results in consequence. Therefore the common method is to reduce the diameter of the modelled granules in order to eliminate the single-point contact between the individual granules. The drawback of such method is the adulteration of flow and contact heat resistance among others. Therefore an innovative method is proposed in the paper: single-point contact is extended to a cylinder-shaped volume contact. Such approach eliminates the low quality mesh elements and simultaneously introduces only slight distortion to the flow as well as contact heat transfer. The performed analysis of numerous test cases prove the great potential of the proposed method of meshing the packed beds of granular materials.

Receiving and use of streams of monodisperse ice granules for cleaning and deactivation of surfaces

NASA Astrophysics Data System (ADS)

Boukharov, A.; Balashov, A.; Timohin, A.; Ivanov, A.; Holin, B.

2017-11-01

The most generally useful methods for cleaning and processing of surfaces are the sand-jets and shot blasting jets. Installations of this kind are used for cleaning of corrosion surfaces, the oil-dirt deposits, paint coatings. However the use of these installations follows to high investment and operational expenditure, larger risk of operators disease, the negative affect for a environment. These problems can be solved with the use of new cleaning method through application of mono-disperse (identical by the size and the form) ice granules of 300 - 1000 microns, accelerated by air stream in the nozzle device to the speed of 10 - 100 m/s. In view of the extreme complexity of the receiving such particles by means of cooling and the subsequent freezing of water drops are necessary additional experimental researches. For study of thermal processes of receiving mono-disperse ice granules the experimental installation was created and experiments on deactivation and cleaning of surfaces with pollution of various types are made. Experiments showed that by means of a stream of the accelerated ice granules it is rather successfully possible to delete oil-dirt deposits, outdated paint coats and rust. Besides, efficient deactivation of radioactive surfaces is possible. The coefficient deactivation of γ activity is highest.

Investigation of drug-excipient compatibility using rheological and thermal tools

NASA Astrophysics Data System (ADS)

Trivedi, Maitri R.

HYPOTHESIS: We plan to investigate a different approach to evaluate drug-excipient physical compatibility using rheological and thermal tools as opposed to commonly used chemical techniques in pharmaceutical industry. This approach offers practical solutions to routinely associated problems arising with API's and commonly used hydrates forms of excipients. ABSTRACT: Drug-Excipient compatibility studies are an important aspect of pre-formulation and formulation development in pharmaceutical research and development. Various approaches have been used in pharmaceutical industry including use of thermal analysis and quantitative assessment of drug-excipient mixtures after keeping the samples under stress environment depending upon the type of formulation. In an attempt to provide better understanding of such compatibility aspect of excipients with different properties of API, various rheological and thermal studies were conducted on binary mixtures of excipients which exist in different hydrates. Dibasic Calcium Phosphate (DCP, anhydrous and dihydrate forms) and Lactose (Lac, anhydrous and monohydrate) were selected with cohesive API's (Acetaminophen and Aspirin). Binary mixtures of DCP and Lac were prepared by addition of 0% w/w to 50% w/w of the API into each powder blend. Rheological and thermal aspects were considered using different approaches such as powder rheometer, rotational shear cell and traditional rheometery approaches like angle of repose (AOR), hausner's ratio (HR) and cares index (CI). Thermal analysis was conducted using modulated differential scanning calorimetry (MDSC) and thermal effusivity. The data suggested that the powder rheometer showed distinctive understanding in the flowability behavior of binary mixtures with addition of increasing proportion of API's than traditional approaches. Thermal approaches revealed the potential interaction of water of crystallization DCP-D with the API (APAP) while such interactions were absent in DCP-A, while in case of Lac-M and Lac-A, interaction with water of crystallization were not present. Binary mixtures prepared with DCP-D were better flowable while blends with DCP-A were better in stability (physical), compressibility and permeability. Similarly binary mixtures prepared with Lac-M were better flowable and stable in physical compatibility as compared to Lac-A. Lac-A were better in compressibility and permeability. Second part of these research included understanding the powder behavior from wet granulation point of view. Wet granulation includes the formation of agglomerates with powders to form granules in order to have better flowability, content uniformity and compressibility of granular mass. End point determination of powders involving change in powder energies and compressibility, permeability along with thermal analyses were conducted. The effects of water of crystallization on end point determination was studied and based on which overall effects on drug-excipient compatibility using different hydrate forms of excipients were evaluated.

Paclitaxel Drug-eluting Tracheal Stent Could Reduce Granulation Tissue Formation in a Canine Model

PubMed Central

Wang, Ting; Zhang, Jie; Wang, Juan; Pei, Ying-Hua; Qiu, Xiao-Jian; Wang, Yu-Ling

2016-01-01

Background: Currently available silicone and metallic stents for tracheal stenosis are associated with many problems. Granulation proliferation is one of the main complications. The present study aimed to evaluate the efficacy of paclitaxel drug-eluting tracheal stent in reducing granulation tissue formation in a canine model, as well as the pharmacokinetic features and safety profiles of the coated drug. Methods: Eight beagles were randomly divided into a control group (bare-metal stent group, n = 4) and an experimental group (paclitaxel-eluting stent group, n = 4). The observation period was 5 months. One beagle in both groups was sacrificed at the end of the 1st and 3rd months, respectively. The last two beagles in both groups were sacrificed at the end of 5th month. The proliferation of granulation tissue and changes in tracheal mucosa were compared between the two groups. Blood routine and liver and kidney function were monitored to evaluate the safety of the paclitaxel-eluting stent. The elution method and high-performance liquid chromatography were used to characterize the rate of in vivo release of paclitaxel from the stent. Results: Compared with the control group, the proliferation of granulation tissue in the experimental group was significantly reduced. The drug release of paclitaxel-eluting stent was the fastest in the 1st month after implantation (up to 70.9%). Then, the release slowed down gradually. By the 5th month, the release reached up to 98.5%. During the observation period, a high concentration of the drug in the trachea (in the stented and adjacent unstented areas) and lung tissue was not noted, and the blood test showed no side effect. Conclusions: The paclitaxel-eluting stent could safely reduce the granulation tissue formation after stent implantation in vivo, suggesting that the paclitaxel-eluting tracheal stent might be considered for potential use in humans in the future. PMID:27824004

The life cycle of platelet granules.

PubMed

Sharda, Anish; Flaumenhaft, Robert

2018-01-01

Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans -Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

Improving the hardness of dry granulated tablets containing sodium lauryl sulfate.

PubMed

Moore, Francis; Okelo, Geoffrey; Colón, Ivelisse; Kushner, Joseph

2010-11-15

The impact of the addition of a wetting agent, the surfactant sodium lauryl sulfate (SLS), on the tablet hardness of a dry granulated, solid oral dosage form was investigated. In three batches, SLS was added concurrently with: (1) a poorly soluble, highly hydrophobic active pharmaceutical ingredient (API) and the other excipients prior to the initial blending step, (2) magnesium stearate prior to roller compaction, or (3) magnesium stearate prior to tableting. A fourth batch, which did not contain SLS, served as a control. The maximum hardness of 100 mg, 1/4″-SRC tablets for the four batches--SLS added initially, prior to roller compaction, prior to tableting, and no SLS--were 61±3, 71±3, 89±5, and 86±3N, respectively, suggesting reduced processing of SLS improves tablet hardness by ∼50%. Dissolution of the tablets in 900 ml of simulated gastric fluid with paddles at 75 rpm showed that: (1) there was no impact on the insertion point of SLS into the process on API dissolution, and (2) that the presence of SLS improved dissolution by 5% compared to the control tablets. Adding SLS just prior to tableting can improve tablet hardness and yield similar dissolution performance relative to SLS addition prior to the initial blending step. Copyright © 2010 Elsevier B.V. All rights reserved.

Influence of enteric-coated lactose on the release profile of 4-aminopyridine from HPMC matrix tablets.

PubMed

Martínez-González, Ilona; Villafuerte-Robles, Leopoldo

2004-01-01

A weakly basic experimental drug, 4-aminopyridine, was taken as a model to study the influence of enteric-coated lactose (EL) on the release profile from hydroxypropyl methylcellulose matrices. Powder mixtures were wet-granulated with water. The dried granulation was compressed with a hydraulic press at 85 MPa. Dissolution studies were made using HCl 0.1 N and then phosphate buffer pH 7.4. Dissolution curves were described by M(t)/M(inf) = k*t(N). A trend toward increasing exponent (n) and decreasing release constant (k) values is observed with increasing EL concentrations up to 9%; this is attributed to an increasing obstruction of the diffusion path by isolated EL particles that are insoluble in HCl and are surrounded by a water-filled space. After a critical EL concentration, the water-filled spaces surrounding EL particles percolate, producing the opposite effect, increasing the release constant and decreasing the exponent (n) values as the EL proportion increases from 10% to 50%. EL particles (2% to 9%) decrease the drug and water transport in matrices dissolving in HCl. Thereafter, at pH 7.4, the pores formed by dissolution of EL particles produce the opposite. Both processes contribute to flattening the release profile. Release profiles with decreasing release constant values show a logarithmic trend toward increasing values of the exponent (n), changing from diffusion toward relaxation-erosion-controlled processes.

Mechanism of the formation of hollow spherical granules using a high shear granulator.

PubMed

Asada, Takumi; Nishikawa, Mitsunori; Ochiai, Yasushi; Noguchi, Shuji; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

2018-05-30

Recently, we have developed a novel granulation technology to manufacture hollow spherical granules (HSGs) for controlled-release formulations; however, the mechanism of the granulation is still unclear. The aim of this study is to determine the mechanism of the formation of the HSGs using a high shear granulator. Samples of granulated material were collected at various times during granulation and were investigated using scanning electron microscope and X-ray computed tomography. It was observed that the granulation proceeded by drug layering to the polymer, followed by formation of a hollow in the granule. In addition, it was also found that generation of a crack in the adhered drug layer and air flow into the granules might be involved in forming the hollow in the structure. Observation of the granulation of formulations with different types of drugs and polymers indicated that negative pressure in the granules occurred and the granules caved in when the hollow was formed. The hollow-forming speed and the shell density of the hollow granules depended on the particular drug and polymer. Taken together, the granulation mechanism of HSGs was determined and this information will be valuable for HSGs technology development. Copyright © 2018 Elsevier B.V. All rights reserved.

Evaluation of Gum of Moringa oleifera as a Binder and Release Retardant in Tablet Formulation

PubMed Central

Panda, D. S.; Choudhury, N. S. K.; Yedukondalu, M.; Si, S.; Gupta, R.

2008-01-01

The present study was undertaken to find out the potential of gum from Moringa oleifera to act as a binder and release retardant in tablet formulations. The effect of calcium sulphate dihydrate (water insoluble) and lactose (water soluble) diluent on the release of propranolol hydrochloride was studied. The DSC thermograms of drug, gum and mixture of gum/drug indicated no chemical interaction. Tablets (F1, F2, F3, and F4) were prepared containing calcium sulphate dihydrate as diluent, propranolol hydrochloride as model drug using 10%, 8%, 6% and 4% w/v of gum solution as binder. Magnesium stearate was used as lubricant. Physical and technological properties of granules and tablets like flow rate, Carr index, Hausner ratio, angle of repose, hardness, friability and disintegration time were determined and found to be satisfactory. Tablets were prepared by wet granulation method containing calcium sulphate dihydrate as excipient, propranolol hydrochloride as model drug using 10%, 20% and 30% of gum as release retardant, magnesium stearate was used as lubricant. Similarly tablets were prepared replacing lactose with calcium sulphate dihydrate. Despite of the widely varying physico-chemical characteristics of the excipients, the drug release profiles were found to be similar. The drug release increased with increasing proportions of the excipient and decreased proportion of the gum irrespective of the solubility characteristics of the excipient. The values of release exponent ‘n’ are between 0.37 and 0.54. This implies that the release mechanism is Fickian. There is no evidence that the dissolution or erosion of the excipient has got any effect on the release of the drug. The t50% values for tablets containing calcium sulphate dihydrate were on an average 10%-15% longer than the tablets containing lactose as excipient. These relatively small differences in t50% values suggest that the nature of excipient used appeared to play a minor role in regulating the release, while the gum content was a major factor. PMID:21394258

Botanical origin, colour, granulation, and sensory properties of the Harenna forest honey, Bale, Ethiopia.

PubMed

Belay, Abera; Solomon, W K; Bultossa, Geremew; Adgaba, Nuru; Melaku, Samuel

2015-01-15

In this study, the Harenna forest honey samples were investigated with respect to their botanical origin, granulation, colour and sensory properties. Sixteen honey samples were collected from two representative sites (Chiri, C, and Wabero, W) using random sampling techniques. Botanical origin was investigated using qualitative pollen analysis by counting 500 pollen grains using harmonised methods of melissopalynology. Granulation, colour, and sensory properties of honey were determined by visual observation, using Pfund grader, acceptability and preference tests, respectively. Honey samples were also tested for tetracycline. Honey obtained from Wabero is originated dominantly from Syzygium guineense while Chiri was multifloral. The colour of honey ranged from 34 to 85 with light amber and extra light amber colours. The honey samples were free from tetracycline residue and form coarse granules slowly. Significant variation (p>0.05) in sensory preference and acceptability tests not observed due to hive types and locations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Copper-granule-catalyzed microwave-assisted click synthesis of polyphenol dendrimers.

PubMed

Lee, Choon Young; Held, Rich; Sharma, Ajit; Baral, Rom; Nanah, Cyprien; Dumas, Dan; Jenkins, Shannon; Upadhaya, Samik; Du, Wenjun

2013-11-15

Syringaldehyde- and vanillin-based antioxidant dendrimers were synthesized via microwave-assisted alkyne-azide 1,3-dipolar cycloaddition using copper granules as a catalyst. The use of Cu(I) as a catalyst resulted in copper contaminated dendrimers. To produce copper-free antioxidant dendrimers for biological applications, Cu(I) was substituted with copper granules. Copper granules were ineffective at both room temperature and under reflux conditions (<5% yield). However, they were an excellent catalyst when dendrimer synthesis was performed under microwave irradiation, giving yields up to 94% within 8 h. ICP-mass analysis of the antioxidant dendrimers obtained with this method showed virtually no copper contamination (9 ppm), which was the same as the background level. The synthesized antioxidants, free from copper contamination, demonstrated potent radical scavenging with IC50 values of less than 3 μM in the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. In comparison, dendrimers synthesized from Cu(I)-catalyzed click chemistry showed a high level of copper contamination (4800 ppm) and no detectable antioxidant activity.

Impact of fill-level in twin-screw granulation on critical quality attributes of granules and tablets.

PubMed

Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

2017-06-01

In a previous study a change of the fill-level in the barrel exerted a huge influence on the twin-screw granulation (TSG) process of a high drug loaded, simplified formulation. The present work investigated this influence systematically. The specific feed load (SFL) indicating the mass per revolution as surrogate parameter for the fill-level was applied and the correlation to the real volumetric fill level of an extruder could be demonstrated by a newly developed method. A design of experiments was conducted to examine the combined influence of SFL and screw speed on the process and on critical quality attributes of granules and tablets. The same formulation was granulated at constant liquid level with the same screw configuration and led to distinctively different results by only changing the fill-level and the screw speed. The power consumption of the extruder increased at higher SFLs with hardly any influence of screw speed. At low SFL the median residence time was mainly fill-level dependent and at higher SFL mainly screw speed dependent. Optimal values for the product characteristics were found at medium values for the SFL. Granule size distributions shifted from mono-modal and narrow shape to broader and even bimodal distributions of larger median granule sizes, when exceeding or falling below a certain fill-level. Deviating from the optimum fill-level, tensile strength of tablets decreased by about 25% and disintegration times of tablets increased for more than one third. At low fill-levels, material accumulation in front of the kneading zone was detected by pressure measurements and was assumed to be responsible for the unfavored product performance. At high fill-levels, granule consolidation due to higher propensity of contact with the result of higher material temperature was accounted for inferior product performance. The fill-level was found to be an important factor in assessment and development of twin-screw granulation processes as it impacted process and product attributes enormously. Copyright © 2017 Elsevier B.V. All rights reserved.

A critical analysis of one standard and five methods to monitor surface wetness and time-of-wetness

NASA Astrophysics Data System (ADS)

Camuffo, Dario; della Valle, Antonio; Becherini, Francesca

2018-05-01

Surface wetness is a synergistic factor to determine atmospheric corrosion, monument weathering, mould growth, sick buildings, etc. However, its detection and monitoring are neither easy nor homogeneous, for a number of factors that may affect readings. Various types of methods and sensors, either commercial or prototypes built in the lab, have been investigated and compared, i.e. the international standard ISO 9223 to evaluate corrosivity after wetness and time-of-wetness; indirect evaluation of wetness, based on the dew point calculated after the output of temperature and relative humidity sensors and direct measurements by means of capacitive wetness sensors, safety sensors, rain sensors (also known as leaf wetness sensors), infrared reflection sensors and fibre optic sensors. A comparison between the different methods is presented, specifying physical principles, forms of wetting to which they are respondent (i.e. condensation, ice melting, splashing drops, percolation and capillary rise), critical factors, use and cost.

Application of High-Performance Liquid Chromatography Coupled with Linear Ion Trap Quadrupole Orbitrap Mass Spectrometry for Qualitative and Quantitative Assessment of Shejin-Liyan Granule Supplements.

PubMed

Gu, Jifeng; Wu, Weijun; Huang, Mengwei; Long, Fen; Liu, Xinhua; Zhu, Yizhun

2018-04-11

A method for high-performance liquid chromatography coupled with linear ion trap quadrupole Orbitrap high-resolution mass spectrometry (HPLC-LTQ-Orbitrap MS) was developed and validated for the qualitative and quantitative assessment of Shejin-liyan Granule. According to the fragmentation mechanism and high-resolution MS data, 54 compounds, including fourteen isoflavones, eleven ligands, eight flavonoids, six physalins, six organic acids, four triterpenoid saponins, two xanthones, two alkaloids, and one licorice coumarin, were identified or tentatively characterized. In addition, ten of the representative compounds (matrine, galuteolin, tectoridin, iridin, arctiin, tectorigenin, glycyrrhizic acid, irigenin, arctigenin, and irisflorentin) were quantified using the validated HPLC-LTQ-Orbitrap MS method. The method validation showed a good linearity with coefficients of determination (r²) above 0.9914 for all analytes. The accuracy of the intra- and inter-day variation of the investigated compounds was 95.0-105.0%, and the precision values were less than 4.89%. The mean recoveries and reproducibilities of each analyte were 95.1-104.8%, with relative standard deviations below 4.91%. The method successfully quantified the ten compounds in Shejin-liyan Granule, and the results show that the method is accurate, sensitive, and reliable.

Improved dissolution and absorption of ketoconazole in the presence of organic acids as pH-modifiers.

PubMed

Adachi, Masashi; Hinatsu, Yuta; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Nakatani, Manabu; Wada, Koichi; Yamamoto, Akira

2015-08-30

Formulation development of poorly water-soluble compounds can be challenging because of incomplete dissolution that causes low and variable bioavailability. Enhancing compound solubility is important and many techniques have been investigated to that end, but they require specific materials and machinery. This study investigates the incorporation of a pH-modifier as a method to increase compound solubility and uses ketoconazole (KZ), which is weakly basic (pKa: 6.5), as a model compound. Organic acids are effective pH-modifiers and are generally used in pharmaceutical industries. We successfully obtained granules containing variable organic acids (KZ/acid granule) using a high-shear mixer. Dissolution tests of the KZ/acid granule resulted in highly enhanced solubility under non-sink conditions. Adding water-soluble acids, such as citric acid (CA) and tartaric acid, resulted in more than 8-fold higher dissolution at pH 6.0 compared to that of KZ only. The granules containing citric acid (KZ/CA granule) improved the dissolution of KZ after oral administration to rats under low gastric acid conditions, where the bioavailability of the KZ/CA granules at elevated gastric pH was comparable with that of KZ only at gastric acidic pH. The incorporation of organic acids would result in effective therapeutic outcomes independent of gastric pH in patients. In addition, higher bioavailability of KZ was observed after oral administration of KZ/CA granules under gastric acidic pH conditions than that of KZ alone. Thus, CA improved the dissolution and absorption rate of KZ after oral administration. Copyright © 2015 Elsevier B.V. All rights reserved.

Influence of preservation temperature on the characteristics of anaerobic ammonium oxidation (anammox) granular sludge.

PubMed

Xing, Bao-Shan; Guo, Qiong; Jiang, Xiao-Yan; Chen, Qian-Qian; Li, Peng; Ni, Wei-Min; Jin, Ren-Cun

2016-05-01

Preserving active anaerobic ammonium oxidation (anammox) biomass is a potential method for securing sufficient seeding biomass for the rapid start-up of full-scale anammox processes. In this study, anammox granules were cultured in an upflow anaerobic sludge blanket (UASB) reactor (R0), and then the enriched anammox granules were preserved at 35, 20, 4, and -30 °C. The subsequent reactivation characteristics of the granules were evaluated in four UASB reactors (denoted R1, R2, R3, and R4, respectively) to investigate the effect of preservation temperature on the characteristics of anammox granules and their reactivation performance. The results demonstrated that 4 °C was the optimal preservation temperature for maintaining the biomass, activity, settleability, and integrity of the anammox granules and their cellular structures. During the preservation period, a first-order exponential decay model may be used to simulate the decay of anammox biomass and activity. The protein-to-polysaccharide ratio in the extracellular polymeric substances and the heme c content could not effectively indicate the changes in settleability and activity of the anammox granules, respectively, and a loss of bioactivity was positively associated with the degree of anaerobic ammonium-oxidizing bacteria cell lysis. After 42 days of storage, the anammox granules preserved at 4 °C (R3) exhibited a better recovery performance than those preserved at 20 °C (R2), -30 °C (R4), and 35 °C (R1). The comprehensive comparison indicated that 4 °C is the optimal storage temperature for anammox granular sludge because it promotes improved maintenance and recovery performance properties.

Evaluation of melt granulation and ultrasonic spray congealing as techniques to enhance the dissolution of praziquantel.

PubMed

Passerini, Nadia; Albertini, Beatrice; Perissutti, Beatrice; Rodriguez, Lorenzo

2006-08-02

Praziquantel (PZQ), an anthelminthic drug widely used in developing countries, is classified in Class II in the Biopharmaceutics Classification Systems; this means that PZQ has very low water solubility and high permeability, thus the dissolution is the absorption rate-limiting factor. The aim of this work was to evaluate the suitability of melt granulation and ultrasonic spray congealing as techniques for enhancing the dissolution rate of PZQ. Granules in high shear mixer were prepared by melt granulation, using polyethylene glycol 4000 or poloxamer 188 as meltable binders and alpha-lactose monohydrate as a filler. Quite regularly shaped granules having main size fraction in the range 200-500 microm were obtained using both formulations; however, only poloxamer 188 granules demonstrated a significant (P=0.05) increase of the PZQ dissolution rate compared to pure drug. To evaluate the potential of ultrasonic spray congealing, Gelucire 50/13 microparticles having different drug to carrier ratios (5, 10, 20 and 30%, w/w) were then prepared. The results showed that all the microparticles had a significant higher dissolution rate (P=0.05) respect to pure PZQ. The increase of the PZQ content considerably decreased the dissolution rate of the drug: 5 and 10% PZQ loaded systems evidenced dissolution significantly enhanced compared to 20 and 30% PZQ microparticles. The microparticle's characterisation, performed by Differential Scanning Calorimetry, Hot Stage Microscopy, X-ray powder diffraction and FT-Infrared analysis, evidenced the absence of both modifications of the solid state of PZQ and of significant interactions between the drug and the carrier. In conclusion, melt granulation and ultrasonic spray congealing could be proposed as solvent free, rapid and low expensive manufacturing methods to increase the in vitro dissolution rate of PZQ.

Super-resolution microscopy as a potential approach to diagnosis of platelet granule disorders.

PubMed

Westmoreland, D; Shaw, M; Grimes, W; Metcalf, D J; Burden, J J; Gomez, K; Knight, A E; Cutler, D F

2016-04-01

Many platelet functions are dependent on bioactive molecules released from their granules. Deficiencies of these granules in number, shape or content are associated with bleeding. The small size of these granules is such that imaging them for diagnosis has traditionally required electron microscopy. However, recently developed super-resolution microscopes provide sufficient spatial resolution to effectively image platelet granules. When combined with automated image analysis, these methods provide a quantitative, unbiased, rapidly acquired dataset that can readily and reliably reveal differences in platelet granules between individuals. To demonstrate the ability of structured illumination microscopy (SIM) to efficiently differentiate between healthy volunteers and three patients with Hermansky-Pudlak syndrome. Blood samples were taken from three patients with Hermansky-Pudlak syndrome and seven controls. Patients 1-3 have gene defects in HPS1, HPS6 and HPS5, respectively; all controls were healthy volunteers. Platelet-rich plasma was isolated from blood and the platelets fixed, stained for CD63 and processed for analysis by immunofluorescence microscopy, using a custom-built SIM microscope. SIM can successfully resolve CD63-positive structures in fixed platelets. A determination of the number of CD63-positive structures per platelet allowed us to conclude that each patient was significantly different from all of the controls with 99% confidence. A super-resolution imaging approach is effective and rapid in objectively differentiating between patients with a platelet bleeding disorder and healthy volunteers. CD63 is a useful marker for predicting Hermansky-Pudlak syndrome and could be used in the diagnosis of patients suspected of other platelet granule disorders. © 2016 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

A quality by design approach using artificial intelligence techniques to control the critical quality attributes of ramipril tablets manufactured by wet granulation.

PubMed

Aksu, Buket; Paradkar, Anant; de Matas, Marcel; Özer, Özgen; Güneri, Tamer; York, Peter

2013-02-01

Quality by design (QbD) is an essential part of the modern approach to pharmaceutical quality. This study was conducted in the framework of a QbD project involving ramipril tablets. Preliminary work included identification of the critical quality attributes (CQAs) and critical process parameters (CPPs) based on the quality target product profiles (QTPPs) using the historical data and risk assessment method failure mode and effect analysis (FMEA). Compendial and in-house specifications were selected as QTPPs for ramipril tablets. CPPs that affected the product and process were used to establish an experimental design. The results thus obtained can be used to facilitate definition of the design space using tools such as design of experiments (DoE), the response surface method (RSM) and artificial neural networks (ANNs). The project was aimed at discovering hidden knowledge associated with the manufacture of ramipril tablets using a range of artificial intelligence-based software, with the intention of establishing a multi-dimensional design space that ensures consistent product quality. At the end of the study, a design space was developed based on the study data and specifications, and a new formulation was optimized. On the basis of this formulation, a new laboratory batch formulation was prepared and tested. It was confirmed that the explored formulation was within the design space.

Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation.

PubMed

Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-Ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

2015-01-01

The effect of some drug properties (wettability and particle size distribution) on granule properties (mean particle size, particle size distribution, sphericity, and granule strength) were investigated in a high (>97%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution. Granules with mean particle sizes of 100-200 µm and a narrow particle size distribution (PSD) could be prepared regardless of the drug used. IBU and ETZ granules showed a higher sphericity than APAP granules, while APAP and ETZ granules exhibited higher granule strength than IBU. The relationship between drug and granule properties suggested that the wettability and the PSD of the drugs were critical parameters affecting sphericity and granule strength, respectively. Furthermore, the dissolution profiles of granules prepared with poorly water-soluble drugs (IBU and ETZ) showed a rapid release (80% release in 20 min) because of the improved wettability with granulation. The present study demonstrated for the first time that fluidized bed rotor granulation can prepare high drug-loaded (>97%) globular granules with a mean particle size of less than 200 µm and the relationship between physicochemical drug properties and the properties of the granules obtained could be readily determined, indicating the potential for further application of this methodology to various drugs.

Phenotypic properties and microbial diversity of methanogenic granules from a full-scale upflow anaerobic sludge bed reactor treating brewery wastewater.

PubMed

Díaz, Emiliano E; Stams, Alfons J M; Amils, Ricardo; Sanz, José L

2006-07-01

Methanogenic granules from an anaerobic bioreactor that treated wastewater of a beer brewery consisted of different morphological types of granules. In this study, the microbial compositions of the different granules were analyzed by molecular microbiological techniques: cloning, denaturing gradient gel electrophoresis and fluorescent in situ hybridization (FISH), and scanning and transmission electron microscopy. We propose here that the different types of granules reflect the different stages in the life cycle of granules. Young granules were small, black, and compact and harbored active cells. Gray granules were the most abundant granules. These granules have a multilayer structure with channels and void areas. The core was composed of dead or starving cells with low activity. The brown granules, which were the largest granules, showed a loose and amorphous structure with big channels that resulted in fractured zones and corresponded to the older granules. Firmicutes (as determined by FISH) and Nitrospira and Deferribacteres (as determined by cloning and sequencing) were the predominant Bacteria. Remarkably, Firmicutes could not be detected in the brown granules. The methanogenic Archaea identified were Methanosaeta concilii (70 to 90% by FISH and cloning), Methanosarcina mazei, and Methanospirillum spp. The phenotypic appearance of the granules reflected the physiological condition of the granules. This may be valuable to easily select appropriate seed sludges to start up other reactors.

Increase in energy efficiency of use of vegetable waste

NASA Astrophysics Data System (ADS)

Safin, R. R.; Safiullina, A. K.; Nazipova, F. V.

2017-10-01

Wastes of woodworking which are exposed to granulation for equalization of humidity, dispersion and also for increase in energy efficiency are the most widespread types of alternative fuel in Russia. Besides, one of the effective methods of the increase in calorific capability of granulates now is the preliminary torrefaction of wood waste - heat treatment without air oxygen access. However this technology is rather researched in detail only in relation to wood particles, while pellets from wastes of agricultural productions are also popular in the market in recent years. The possibility of the increase of the efficiency of production of pellets from sunflower pod by torrefaction is considered in this article, and the analysis of their characteristics in comparison with wood pellets is carried out. It is established that the process of heat treatment of waste of sunflower production is similar to torrefaction of wood raw materials in many respects; therefore, the equipment with similar characteristics can be used. According to the received results on pellet’s properties it is established that hygroscopicity and swelling of samples of fuel granules from sunflower pod considerably decreases with the increase in temperature of treatment that simplifies requirements for their storage and transportation. Besides, it is defined that torrefaction of the granulated fuel from sunflower pod does not yield in calorific properties to the similar fuel granules made of wood sawdust. Thus feasibility of use of heat treatment in production of fuel granules from waste of vegetable raw materials is proved.

Microbial community variation in cryoconite granules on Qaanaaq Glacier, NW Greenland.

PubMed

Uetake, Jun; Tanaka, Sota; Segawa, Takahiro; Takeuchi, Nozomu; Nagatsuka, Naoko; Motoyama, Hideaki; Aoki, Teruo

2016-09-01

Cryoconite granules are aggregations of microorganisms with mineral particles that form on glacier surfaces. To understand the processes by which the granules develop, this study focused on the altitudinal distribution of the granules and photosynthetic microorganisms on the glacier, bacterial community variation with granules size and environmental factors affecting the growth of the granules. Size-sorted cryoconite granules collected from five different sites on Qaanaaq Glacier were analyzed. C and N contents were significantly higher in large (diameter greater than 250 μm) granules than in smaller (diameter 30-249 μm) granules. Bacterial community structures, based on 16S rRNA gene amplicon sequencing, were different between the smaller and larger granules. The filamentous cyanobacterium Phormidesmis priestleyi was the dominant bacterial species in larger granules. Multivariate analysis suggests that the abundance of mineral particles on the glacier surface is the main factor controlling growth of these cyanobacteria. These results show that the supply of mineral particles on the glacier enhances granule development, that P. priestleyi is likely the key species for primary production and the formation of the granules and that the bacterial community in the granules changes over the course of the granule development. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Rapid microwave fixation of rat mast cells. I. Localization of granule chymase with an ultrastructural postembedding immunogold technique.

PubMed

Login, G R; Galli, S J; Morgan, E; Arizono, N; Schwartz, L B; Dvorak, A M

1987-11-01

We defined the ultrastructural localization of chymase in rat peritoneal mast cells using standard aldehyde fixation and a newly described microwave fixation method (Login GR, Dvorak AM: Microwave energy fixation for electron microscopy. Am J Pathol 120: 230, 1985; Login GR, Stavinoha WB, Dvorak AM: Ultrafast microwave energy fixation for electron microscopy. J Histochem Cytochem 34:381, 1986) and postembedding immunogold labeling. Thin sections were exposed first to goat IgG anti-rat chymase and second to gold-conjugated rabbit Ig directed against goat IgG. By transmission electron microscopy, gold particles were localized to the matrix of cytoplasmic granules. Control sections treated with nonimmune sera did not exhibit labeling of mast cells. Thin sections treated simultaneously with purified rat mast cell chymase and anti-chymase antibody in competition studies, showed a marked reduction in granule staining. These findings demonstrate that a microwave fixation method can be used to rapidly fix cell suspensions for postembedding immunocytochemical studies.

Cytoplasmic RNA Granules in Somatic Maintenance.

PubMed

Moujaber, Ossama; Stochaj, Ursula

2018-05-30

Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional "operons". RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies. © 2018 S. Karger AG, Basel.

Rational preparation of waste coal mixture for production of bricks by the method of compression molding

NASA Astrophysics Data System (ADS)

Stolboushkin, A. Yu; Ivanov, A. I.; Temlyantsev, M. V.; Fomina, O. A.

2016-10-01

Rational preparation of the mixture containing technogenic raw material - waste coal for the production of wall ceramics is developed. It was established that the technology of high-quality ceramic bricks requires: grinding of raw materials to class 0.3 + 0 mm, its aggregation in the intensive mixers into granules 1-3 mm, compression molding of adobe to plastic deformation of granules, drying and firing.

Numerical analysis of temperature field in the high speed rotary dry-milling process

NASA Astrophysics Data System (ADS)

Wu, N. X.; Deng, L. J.; Liao, D. H.

2018-01-01

For the effect of the temperature field in the ceramic dry granulation. Based on the Euler-Euler mathematical model, at the same time, made ceramic dry granulation experiment equipment more simplify and established physical model, the temperature of the dry granulation process was simulated with the granulation time. The relationship between the granulation temperature and granulation effect in dry granulation process was analyzed, at the same time, the correctness of numerical simulation was verified by measuring the fluidity index of ceramic bodies. Numerical simulation and experimental results showed that when granulation time was 4min, 5min, 6min, maximum temperature inside the granulation chamber was: 70°C, 85°C, 95°C. And the equilibrium of the temperature in the granulation chamber was weakened, the fluidity index of the billet particles was: 56.4. 89.7. 81.6. Results of the research showed that when granulation time was 5min, the granulation effect was best. When the granulation chamber temperature was more than 85°C, the fluidity index and the effective particles quantity of the billet particles were reduced.

CaMKIIalpha 3' untranslated region-directed mRNA translocation in living neurons: visualization by GFP linkage

NASA Technical Reports Server (NTRS)

Rook, M. S.; Lu, M.; Kosik, K. S.

2000-01-01

The CaMKIIalpha mRNA extends into distal hippocampal dendrites, and the 3' untranslated region (3'UTR) is sufficient to mediate this localization. We labeled the 3'UTR of the CaMKIIalpha mRNA in hippocampal cultures by using a green fluorescent protein (GFP)/MS2 bacteriophage tagging system. The CaMKIIalpha 3'UTR formed discrete granules throughout the dendrites of transfected cells. The identity of the fluorescent granules was verified by in situ hybridization. Over 30 min time periods these granules redistributed without a net increase in granule number; with depolarization there is a tendency toward increased numbers of granules in the dendrites. These observations suggest that finer time resolution of granule motility might reveal changes in the motility characteristics of granules after depolarization. So that motile granules could be tracked, shorter periods of observation were required. The movements of motile granules can be categorized as oscillatory, unidirectional anterograde, or unidirectional retrograde. Colocalization of CaMKIIalpha 3'UTR granules and synapses suggested that oscillatory movements allowed the granules to sample several local synapses. Neuronal depolarization increased the number of granules in the anterograde motile pool. Based on the time frame over which the granule number increased, the translocation of granules may serve to prepare the dendrite for mounting an adequate local translation response to future stimuli. Although the resident pool of granules can respond to signals that induce local translation, the number of granules in a dendrite might reflect its activation history.

Effect of granular activated carbon on the aerobic granulation of sludge and its mechanism.

PubMed

Tao, Jia; Qin, Lian; Liu, Xiaoying; Li, Bolin; Chen, Junnan; You, Juan; Shen, Yitian; Chen, Xiaoguo

2017-07-01

The granulation of activated sludge and effect of granular activated carbon (GAC) was investigated under the alternative anaerobic and aerobic conditions. The results showed that GAC accelerated the granulation, but had no obvious effect on the bacterial community structure of granules. The whole granulation process could be categorized into three phases, i.e. lag, granulation and granule maturation phase. During lag period GAC provided nuclei for sludge to attach, and thus enhanced the morphological regularization of sludge. During granulation period the granule size increased significantly due to the growth of bacteria in granules. GAC reduced the compression caused by the inter-particle collisions and thus accelerate the granulation. GAC has no negative effect on the performance of SBR, and thus efficient simultaneous removal of COD, nitrogen and phosphorus were obtained during most of the operating time. Copyright © 2017. Published by Elsevier Ltd.

[The application of full thicknes skin graft inpartial laryngectomy for glottic carcinoma].

PubMed

Fu, Y G; Sun, D Z; Yang, P Z; Chen, Y L; Chen, Z P; Yang, Z K

2016-08-05

Objective: The aim of this study is to explore the experience and advantages of the application of full thicknes skin graft in glottic carcinoma.partial laryngectomy for glottic carcinoma. Method: One hundred and forty-three patients with glottic cancer were treated with partial laryngectomy.Among those,78 cases were repaired with full-thickness skin graft and 65 cases were repaired with sternohyoid muscular fasciae.Compared the time of extubation and the formation of granulation in laryngeal cavity after operation between the two groups. Result: In the group of full-thickness skin graft,the mean time of decannulation was 6.8 days,5 cases with growth of granulation after operation.In other group,the mean time of decannulation was 10.7 days,16 cases with growth of granulation after operation.The mean time of decannulation( t =-4.739, P <0.01) and the growth of granulation(χ²=9.379, P <0.01) are significantly different between the two groups.No laryngostenosis was found in all patients. Conclusion: The application of full-thicknes skin graft in partial laryngectomy for glottic carcinoma.can shortthe time of extubation and reduce the formation of granulation. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules II. effects of the binder solution on the release process.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2004-03-01

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC) matrix granules prepared by an extrusion granulation method were examined. The release process could be divided into two parts; the first and second stages were analyzed by applying square-root time law and cube-root law equations, respectively. The validity of the treatments was confirmed by the fitness of a simulation curve with the measured curve. In the first stage, PPA was released from the gel layer of swollen EC in the matrix granules. In the second stage, the drug existing below the gel layer dissolved and was released through the gel layer. The effect of the binder solution on the release from EC matrix granules was also examined. The binder solutions were prepared from various EC and ethanol (EtOH) concentrations. The media changed from a good solvent to a poor solvent with decreasing EtOH concentration. The matrix structure changed from loose to compact with increasing EC concentration. The preferable EtOH concentration region was observed when the release process was easily predictable. The time and release ratio at the connection point of the simulation curves were also examined to determine the validity of the analysis.

Quantification of high-power ultrasound induced damage on potato starch granules using light microscopy.

PubMed

Zuo, Yue Yue J; Hébraud, Pascal; Hemar, Yacine; Ashokkumar, Muthupandian

2012-05-01

A simple light microscopic technique was developed in order to quantify the damage inflicted by high-power low-frequency ultrasound (0-160 W, 20 kHz) treatment on potato starch granules in aqueous dispersions. The surface properties of the starch granules were modified using ethanol and SDS washing methods, which are known to displace proteins and lipids from the surface of the starch granules. The study showed that in the case of normal and ethanol-washed potato starch dispersions, two linear regions were observed. The number of defects first increased linearly with an increase in ultrasound power up to a threshold level. This was then followed by another linear dependence of the number of defects on the ultrasound power. The power threshold where the change-over occurred was higher for the ethanol-washed potato dispersions compared to non-washed potato dispersions. In the case of SDS-washed potato starch, although the increase in defects was linear with the ultrasound power, the power threshold for a second linear region was not observed. These results are discussed in terms of the different possible mechanisms of cavitation induced-damage (hydrodynamic shear stresses and micro-jetting) and by taking into account the hydrophobicity of the starch granule surface. Copyright © 2011 Elsevier B.V. All rights reserved.

Determining particle size and water content by near-infrared spectroscopy in the granulation of naproxen sodium.

PubMed

Bär, David; Debus, Heiko; Brzenczek, Sina; Fischer, Wolfgang; Imming, Peter

2018-03-20

Near-infrared spectroscopy is frequently used by the pharmaceutical industry to monitor and optimize several production processes. In combination with chemometrics, a mathematical-statistical technique, the following advantages of near-infrared spectroscopy can be applied: It is a fast, non-destructive, non-invasive, and economical analytical method. One of the most advanced and popular chemometric technique is the partial least square algorithm with its best applicability in routine and its results. The required reference analytic enables the analysis of various parameters of interest, for example, moisture content, particle size, and many others. Parameters like the correlation coefficient, root mean square error of prediction, root mean square error of calibration, and root mean square error of validation have been used for evaluating the applicability and robustness of these analytical methods developed. This study deals with investigating a Naproxen Sodium granulation process using near-infrared spectroscopy and the development of water content and particle-size methods. For the water content method, one should consider a maximum water content of about 21% in the granulation process, which must be confirmed by the loss on drying. Further influences to be considered are the constantly changing product temperature, rising to about 54 °C, the creation of hydrated states of Naproxen Sodium when using a maximum of about 21% water content, and the large quantity of about 87% Naproxen Sodium in the formulation. It was considered to use a combination of these influences in developing the near-infrared spectroscopy method for the water content of Naproxen Sodium granules. The "Root Mean Square Error" was 0.25% for calibration dataset and 0.30% for the validation dataset, which was obtained after different stages of optimization by multiplicative scatter correction and the first derivative. Using laser diffraction, the granules have been analyzed for particle sizes and obtaining the summary sieve sizes of >63 μm and >100 μm. The following influences should be considered for application in routine production: constant changes in water content up to 21% and a product temperature up to 54 °C. The different stages of optimization result in a "Root Mean Square Error" of 2.54% for the calibration data set and 3.53% for the validation set by using the Kubelka-Munk conversion and first derivative for the near-infrared spectroscopy method for a particle size >63 μm. For the near-infrared spectroscopy method using a particle size >100 μm, the "Root Mean Square Error" was 3.47% for the calibration data set and 4.51% for the validation set, while using the same pre-treatments. - The robustness and suitability of this methodology has already been demonstrated by its recent successful implementation in a routine granulate production process. Copyright © 2018 Elsevier B.V. All rights reserved.

[Influence of electroacupuncture with penetration needling method on comprehensive pain score in patients with cervical spondylotic radiculopathy].

PubMed

Wan, Bi-Jiang; Huang, Wei; Zhang, Ya-Xi; Zhang, Huang-Sheng

2013-05-01

To compare the efficacy differences among electroacupuncture with penetration needling method, Jiaji electroacupuncture and Jing fukang granule for cervical spondylotic radiculopathy (CSR) and to explore the best therapeutic method. One hundred and sixty patients with CSR were randomly divided into 3 groups. Sixty patients in electroacupuncture with penetration needling method group (group A) were treated by electroacupuncture with penetration needling method, and C4 Jiaji-to-C7 Jiaji, Jianwaishu (SI 14)-to-Quyuan (SI 13), Tianzong (SI 11)-to-Naoshu (SI 10), Shousanli (LI 10)-to-Xialian (LI 8) were selected, once a day. Sixty patients in Jiaji electroacupuncture group (group B) were treated by Jiaji electroacupuncture at C4 Jiaji-to-C7 Jiaji, once a day. Fourty patients in Jing fukang granule group (group C) were treated by oral administration of Jing fukang granule, 1 bag each time, twice each day. Six days as a course, the 3 groups were all treated for two courses. The simplified MPQ (SF-MPQ) scale which was internationally accepted was adopt to evaluate the improving situations in pain. After treatment, pain rating idex (PRI), visual analogue scale (VAS), present pain intensity (PPI) and the total pain score were significantly improved in the group A and B compared with those before treatment (all P < 0.01), which was also improved in the group C (all P < 0.05). Compared with the group C, all the scores were significantly improved in the group A (all P < 0.01), the improvement of PRI, VAS, PPI and total pain score in the group B was superior to those in the group C (all P < 0.05), and all the improvements in the group A were superior to those in the group B (P < 0.05, P < 0.01). Electroacupuncture with penetration needling method can relive pain rapaidly in patients with CSR, which is superior to Jiaji electroacupuncture and Jing fukang granule in improving the comprehensive pain scores.

Cellular stress induces cytoplasmic RNA granules in fission yeast.

PubMed

Nilsson, Daniel; Sunnerhagen, Per

2011-01-01

Severe stress causes plant and animal cells to form large cytoplasmic granules containing RNA and proteins. Here, we demonstrate the existence of stress-induced cytoplasmic RNA granules in Schizosaccharomyces pombe. Homologs to several known protein components of mammalian processing bodies and stress granules are found in fission yeast RNA granules. In contrast to mammalian cells, poly(A)-binding protein (Pabp) colocalizes in stress-induced granules with decapping protein. After glucose deprivation, protein kinase A (PKA) is required for accumulation of Pabp-positive granules and translational down-regulation. This is the first demonstration of a role for PKA in RNA granule formation. In mammals, the translation initiation protein eIF2α is a key regulator of formation of granules containing poly(A)-binding protein. In S. pombe, nonphosphorylatable eIF2α does not block but delays granule formation and subsequent clearance after exposure to hyperosmosis. At least two separate pathways in S. pombe appear to regulate stress-induced granules: pka1 mutants are fully proficient to form granules after hyperosmotic shock; conversely, eIF2α does not affect granule formation in glucose starvation. Further, we demonstrate a Pka1-dependent link between calcium perturbation and RNA granules, which has not been described earlier in any organism.

Deficiency of Starch Synthase IIIa and IVb Alters Starch Granule Morphology from Polyhedral to Spherical in Rice Endosperm1

PubMed Central

Toyosawa, Yoshiko; Kawagoe, Yasushi; Matsushima, Ryo; Ogawa, Masahiro; Fukuda, Masako; Kumamaru, Toshihiro; Okazaki, Yozo; Kusano, Miyako; Saito, Kazuki; Toyooka, Kiminori; Sato, Mayuko; Ai, Yongfeng; Fujita, Naoko

2016-01-01

Starch granule morphology differs markedly among plant species. However, the mechanisms controlling starch granule morphology have not been elucidated. Rice (Oryza sativa) endosperm produces characteristic compound-type granules containing dozens of polyhedral starch granules within an amyloplast. Some other cereal species produce simple-type granules, in which only one starch granule is present per amyloplast. A double mutant rice deficient in the starch synthase (SS) genes SSIIIa and SSIVb (ss3a ss4b) produced spherical starch granules, whereas the parental single mutants produced polyhedral starch granules similar to the wild type. The ss3a ss4b amyloplasts contained compound-type starch granules during early developmental stages, and spherical granules were separated from each other during subsequent amyloplast development and seed dehydration. Analysis of glucan chain length distribution identified overlapping roles for SSIIIa and SSIVb in amylopectin chain synthesis, with a degree of polymerization of 42 or greater. Confocal fluorescence microscopy and immunoelectron microscopy of wild-type developing rice seeds revealed that the majority of SSIVb was localized between starch granules. Therefore, we propose that SSIIIa and SSIVb have crucial roles in determining starch granule morphology and in maintaining the amyloplast envelope structure. We present a model of spherical starch granule production. PMID:26747287

High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions.

PubMed

Rice, W G; Kinkade, J M; Parmley, R T

1986-08-01

Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA-TCH-SP staining of isolated granule fractions revealed patterns similar to those of granules in intact neutrophils at different stages of development. Granules from human acute promyelocytic leukemia cells (HL-60) exhibited a surprisingly low density compared with typical azurophil granules from normal, mature neutrophils. The data suggest that both functional and maturational differences contribute to granule heterogeneity, and provide a new practical and conceptual framework for further defining the phenomenon of neutrophil granule heterogeneity.

Method for wetting a boron alloy to graphite

DOEpatents

Storms, E.K.

1987-08-21

A method is provided for wetting a graphite substrate and spreading a a boron alloy over the substrate. The wetted substrate may be in the form of a needle for an effective ion emission source. The method may also be used to wet a graphite substrate for subsequent joining with another graphite substrate or other metal, or to form a protective coating over a graphite substrate. A noneutectic alloy of boron is formed with a metal selected from the group consisting of nickel (Ni), palladium (Pd), and platinum (Pt) with excess boron, i.e., and atomic percentage of boron effective to precipitate boron at a wetting temperature of less than the liquid-phase boundary temperature of the alloy. The alloy is applied to the substrate and the graphite substrate is then heated to the wetting temperature and maintained at the wetting temperature for a time effective for the alloy to wet and spread over the substrate. The excess boron is evenly dispersed in the alloy and is readily available to promote the wetting and spreading action of the alloy. 1 fig.

Intracisternal granules in the adipokinetic cells of locusts are not degraded and apparently function as supplementary stores of secretory material.

PubMed

Harthoorn, L F; Diederen, J H; Oudejans, R C; Verstegen, M M; Vullings, H G; Van der Horst, D J

2000-01-01

The intracisternal granules in locust adipokinetic cells appear to represent accumulations of secretory material within cisternae of the rough endoplasmic reticulum. An important question is whether these granules are destined for degradation or represent stores of (pro)hormones. Two strategies were used to answer this question. First, cytochemistry was applied to elucidate the properties of intracisternal granules. The endocytic tracers horseradish peroxidase and wheat-germ agglutinin-conjugated horseradish peroxidase were used to facilitate the identification of endocytic, autophagic, and lysosomal organelles, which may be involved in the degradation of intracisternal granules. No intracisternal granules could be found within autophagosomes, and granules fused with endocytic and lysosomal organelles were not observed, nor could tracer be found within the granules. The lysosomal enzyme acid phosphatase was absent from the granules. Second, biochemical analysis of the content of intracisternal granules revealed that these granules contain prohormones as well as hormones. Prohormones were present in relatively higher amounts compared with ordinary secretory granules. Since the intracisternal granules in locust adipokinetic cells are not degraded and contain intact (pro)hormones it is concluded that they function as supplementary stores of secretory material.

Screening and identification of α-glucosidase inhibitors from Shenqi Jiangtang Granule by ultrafiltration liquid chromatography and mass spectrometry.

PubMed

Zhang, Hui; Zhang, Xiaojing; Jiang, Huijie; Xu, Cong; Tong, Shengqiang; Yan, Jizhong

2018-02-01

Shenqi Jiangtang Granule, a well-known traditional Chinese herbal preparation, has been widely used for the treatment of type II diabetes mellitus. In this work, an ultrafiltration liquid chromatography with quadrupole time-of-flight mass spectrometry method was proposed for the rapid identification of bioactive ingredients from Shenqi Jiangtang Granule using α-glucosidase as an example. First, the chemical profile of this preparation was clarified, including 37 saponins, 17 flavonoids, 37 lignans, and seven other compounds. After incubation with α-glucosidase in vitro, the methanol extract with an IC 50 value of 0.19 mg/mL exhibited significant inhibitory activity. Then, 18 specific binding peaks were screened, and 15 peaks were identified. Among these, ten compounds were reported to have potential α-glucosidase inhibitory activity for the first time. Subsequently, the inhibitory activities of these active compounds were evaluated by ultraviolet spectrophotometry with p-nitrophenyl α-d-glucopyranoside as a substrate. As a result, gomisin J and gomisin D exhibited stronger α-glucosidase inhibitory activities than other active compounds with IC 50 values of 77.69 and 133.85 μM, respectively. The results demonstrated that the integrated ultrafiltration liquid chromatography with mass spectrometry method was an effective and powerful tool for the discovery of active ingredients in Shenqi Jiangtang Granule. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tempe Waste Water Degradation Using TiO2-N/Bentonite alginate Granule Photocatalyst with Ultraviolet Light Irradiation

NASA Astrophysics Data System (ADS)

Khoirun Nisaa', Aldila; Wardhani, Sri; Purwonugroho, Danar; Darjito

2018-01-01

Tempe waste water stew has high ammonia concentration which causes odor due to polluting by anaerobic decay. Free ammonia in the waste has exceeded the limit, thus endangering the aquatic environment. This research aims to determine the activity of photocatalyst granule TiO2-N/bentonite-alginate as decomposers of compounds in the photodegradation process. Photodegradation is the decomposition process of compounds by semiconductors with light. Results expected includes the photocatalyst activity of TiO2-N/bentonite-alginate granule produced by ultraviolet rays is known based on the effect of dopant N concentration on the catalyst and the effect of photocatalytic ratio toward tempe waste water. Methods proposed in this research are activation of bentonite using H2SO4 0.8 M, TiO2-N synthesize by sonication method with urea as the source of N, then TiO2-N impregnation into bentonite. Photocatalyst in granule form synthesized with alginate was then dripped with syringe pump into 3% (w/v) CaCl2. The photocatalyst characterization will be performed using XRD. The optimum tempe waste water degradation at the concentration of TiO2-N 0.4 (g/g) bentonite is 53.66%. The ratio of photocatalyst and tempe waste water, optimum at 150 mg of photocatalyst with 25 mL of waste equal to 53.66%.

A new method suitable for calculating accurately wetting temperature over a wide range of conditions: Based on the adaptation of continuation algorithm to classical DFT

NASA Astrophysics Data System (ADS)

Zhou, Shiqi

2017-11-01

A new scheme is put forward to determine the wetting temperature (Tw) by utilizing the adaptation of arc-length continuation algorithm to classical density functional theory (DFT) used originally by Frink and Salinger, and its advantages are summarized into four points: (i) the new scheme is applicable whether the wetting occurs near a planar or a non-planar surface, whereas a zero contact angle method is considered only applicable to a perfectly flat solid surface, as demonstrated previously and in this work, and essentially not fit for non-planar surface. (ii) The new scheme is devoid of an uncertainty, which plagues a pre-wetting extrapolation method and originates from an unattainability of the infinitely thick film in the theoretical calculation. (iii) The new scheme can be similarly and easily applied to extreme instances characterized by lower temperatures and/or higher surface attraction force field, which, however, can not be dealt with by the pre-wetting extrapolation method because of the pre-wetting transition being mixed with many layering transitions and the difficulty in differentiating varieties of the surface phase transitions. (iv) The new scheme still works in instance wherein the wetting transition occurs close to the bulk critical temperature; however, this case completely can not be managed by the pre-wetting extrapolation method because near the bulk critical temperature the pre-wetting region is extremely narrow, and no enough pre-wetting data are available for use of the extrapolation procedure.

Rapid Feedforward Inhibition and Asynchronous Excitation Regulate Granule Cell Activity in the Mammalian Main Olfactory Bulb

PubMed Central

Burton, Shawn D.

2015-01-01

Granule cell-mediated inhibition is critical to patterning principal neuron activity in the olfactory bulb, and perturbation of synaptic input to granule cells significantly alters olfactory-guided behavior. Despite the critical role of granule cells in olfaction, little is known about how sensory input recruits granule cells. Here, we combined whole-cell patch-clamp electrophysiology in acute mouse olfactory bulb slices with biophysical multicompartmental modeling to investigate the synaptic basis of granule cell recruitment. Physiological activation of sensory afferents within single glomeruli evoked diverse modes of granule cell activity, including subthreshold depolarization, spikelets, and suprathreshold responses with widely distributed spike latencies. The generation of these diverse activity modes depended, in part, on the asynchronous time course of synaptic excitation onto granule cells, which lasted several hundred milliseconds. In addition to asynchronous excitation, each granule cell also received synchronous feedforward inhibition. This inhibition targeted both proximal somatodendritic and distal apical dendritic domains of granule cells, was reliably recruited across sniff rhythms, and scaled in strength with excitation as more glomeruli were activated. Feedforward inhibition onto granule cells originated from deep short-axon cells, which responded to glomerular activation with highly reliable, short-latency firing consistent with tufted cell-mediated excitation. Simulations showed that feedforward inhibition interacts with asynchronous excitation to broaden granule cell spike latency distributions and significantly attenuates granule cell depolarization within local subcellular compartments. Collectively, our results thus identify feedforward inhibition onto granule cells as a core feature of olfactory bulb circuitry and establish asynchronous excitation and feedforward inhibition as critical regulators of granule cell activity. SIGNIFICANCE STATEMENT Inhibitory granule cells are involved critically in shaping odor-evoked principal neuron activity in the mammalian olfactory bulb, yet little is known about how sensory input activates granule cells. Here, we show that sensory input to the olfactory bulb evokes a barrage of asynchronous synaptic excitation and highly reliable, short-latency synaptic inhibition onto granule cells via a disynaptic feedforward inhibitory circuit involving deep short-axon cells. Feedforward inhibition attenuates local depolarization within granule cell dendritic branches, interacts with asynchronous excitation to suppress granule cell spike-timing precision, and scales in strength with excitation across different levels of sensory input to normalize granule cell firing rates. PMID:26490853

Influence of temporary organic bond nature on the properties of compacts and ceramics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ditts, A., E-mail: ditts@tpu.ru; Revva, I., E-mail: revva@tpu.ru; Pogrebenkov, V.

2016-01-15

This work contains results of investigation of obtaining high thermally conductive ceramics from commercial powders of aluminum nitride and yttrium oxide by the method of monoaxial compaction of granulate. The principal scheme of preparation is proposed and technological properties of granulate are defined. Compaction conditions for simple items to use as heat removal in microelectronics and power electrical engineering have been established. Investigations of thermophysical properties of obtained ceramics and its structure by the XRD and SEM methods have been carried out. Ceramics with thermal conductivity from 172 to 174 W/m·K has been obtained as result of this work.

Modeling of feed-forward control using the partial least squares regression method in the tablet compression process.

PubMed

Hattori, Yusuke; Otsuka, Makoto

2017-05-30

In the pharmaceutical industry, the implementation of continuous manufacturing has been widely promoted in lieu of the traditional batch manufacturing approach. More specially, in recent years, the innovative concept of feed-forward control has been introduced in relation to process analytical technology. In the present study, we successfully developed a feed-forward control model for the tablet compression process by integrating data obtained from near-infrared (NIR) spectra and the physical properties of granules. In the pharmaceutical industry, batch manufacturing routinely allows for the preparation of granules with the desired properties through the manual control of process parameters. On the other hand, continuous manufacturing demands the automatic determination of these process parameters. Here, we proposed the development of a control model using the partial least squares regression (PLSR) method. The most significant feature of this method is the use of dataset integrating both the NIR spectra and the physical properties of the granules. Using our model, we determined that the properties of products, such as tablet weight and thickness, need to be included as independent variables in the PLSR analysis in order to predict unknown process parameters. Copyright © 2017 Elsevier B.V. All rights reserved.

Conching Chocolate

NASA Astrophysics Data System (ADS)

Hunter, Gary L.; Chaikin, Paul; Blanco, Elena; Poon, Wilson

2014-03-01

``Conching'' is an intermediate step in the processing of chocolate where hydrophilic solid particles, such as sugar and milk proteins, are aggressively mixed into a fatty, fluid phase containing emulsifier, e.g. molten cocoa butter with lecithin. During conching, the system evolves from a fine powder to a coarser granulated material and ultimately into a thick cohesive paste. Our goal is to better understand the evolution of chocolate during conching and the transition from an effectively dry to a wet or immersed granular material. In particular, we focus on how mixing times change in response to variations in solid particle volume fractions and emulsifier concentration. As a function of volume fraction, mixing times are well-described by a conventional form that diverges at a finite volume fraction. Furthermore, mixing times can be collapsed onto a universal curve as a function of mixing speed and emulsifier concentration.

Carbon nanotube fiber spun from wetted ribbon

DOEpatents

Zhu, Yuntian T; Arendt, Paul; Zhang, Xiefei; Li, Qingwen; Fu, Lei; Zheng, Lianxi

2014-04-29

A fiber of carbon nanotubes was prepared by a wet-spinning method involving drawing carbon nanotubes away from a substantially aligned, supported array of carbon nanotubes to form a ribbon, wetting the ribbon with a liquid, and spinning a fiber from the wetted ribbon. The liquid can be a polymer solution and after forming the fiber, the polymer can be cured. The resulting fiber has a higher tensile strength and higher conductivity compared to dry-spun fibers and to wet-spun fibers prepared by other methods.

Difference in distribution of membrane proteins between low- and high-density secretory granules in parotid acinar cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujita-Yoshigaki, Junko; Katsumata, Osamu; Matsuki, Miwako

Secretory granules (SGs) are considered to be generated as immature granules and to mature by condensation of their contents. In this study, SGs of parotid gland were separated into low-, medium-, and high-density granule fractions by Percoll-density gradient centrifugation, since it was proposed that the density corresponds to the degree of maturation. The observation with electron microscopy showed that granules in the three fractions were very similar. The average diameter of high-density granules was a little but significantly larger than that of low-density granules. Although the three fractions contained amylase, suggesting that they are all SGs, distribution of membrane proteinsmore » was markedly different. Syntaxin6 and VAMP4 were localized in the low-density granule fraction, while VAMP2 was concentrated in the high-density granule fraction. Immunoprecipitation with anti-syntaxin6 antibody caused coprecipitation of VAMP2 from the medium-density granule fraction without solubilization, but not from Triton X-100-solubilized fraction, while VAMP4 was coprecipitated from both fractions. Therefore, VAMP2 is present on the same granules, but is separated from syntaxin6 and VAMP4, which are expected to be removed from immature granules. These results suggest that the medium-density granules are intermediates from low- to high-density granules, and that the membrane components of SGs dynamically change by budding and fusion during maturation.« less

PHB granules are attached to the nucleoid via PhaM in Ralstonia eutropha.

PubMed

Wahl, Andreas; Schuth, Nora; Pfeiffer, Daniel; Nussberger, Stephan; Jendrossek, Dieter

2012-11-16

Poly(3-hydroxybutyrate) (PHB) granules are important storage compounds of carbon and energy in many prokaryotes which allow survival of the cells in the absence of suitable carbon sources. Formation and subcellular localization of PHB granules was previously assumed to occur randomly in the cytoplasm of PHB accumulating bacteria. However, contradictionary results on subcellular localization of PHB granules in Ralstonia eutropha were published, recently. Here, we provide evidence by transmission electron microscopy that PHB granules are localized in close contact to the nucleoid region in R. eutropha during growth on nutrient broth. Binding of PHB granules to the nucleoid is mediated by PhaM, a PHB granule associated protein with phasin-like properties that is also able to bind to DNA and to phasin PhaP5. Over-expression of PhaM resulted in formation of many small PHB granules that were always attached to the nucleoid region. In contrast, PHB granules of ∆phaM strains became very large and distribution of granules to daughter cells was impaired. Association of PHB granules to the nucleoid region was prevented by over-expression of PhaP5 and clusters of several PHB granules were mainly localized near the cell poles. Subcellular localization of PHB granules is controlled in R. eutropha and depends on the presence and concentrations of at least two PHB granule associated proteins, PhaM and PhaP5.

Sodium phenylbutyrate coated granules (Pheburane). Defective urea synthesis: a welcome formulation.

PubMed

2015-02-01

Compared with Ammonaps granules, Pheburane coated granules mask the unpleasant taste of sodium phenylbutyrate. A more precise dosing device is provided with the coated granules than with the uncoated granules (Ammonaps).

Study on acute toxicity of anti-vertigo granule on mice

NASA Astrophysics Data System (ADS)

Wen, Zhonghua; Hao, Shaojun; Xie, Guoqi; Li, Jun; Su, Feng; Liu, Xiaobin; Wang, Xidong; Zhang, Zhengchen

2018-04-01

To observe the effect of anti - glare particles on acute toxicity of mice. Methods: 40 male and female mice weighing 18 - 21 g were randomly divided into anti - glare granule group and normal saline control group. The maximum volume of anti - glare particles (0.94 g/ml) was administered before the experiment. Results: the oral toxicity of the suspension was very small. The maximal concentration of mice was given at the maximum volume of gastric perfusion, and it was given three times in 1st. The cumulative maximum tolerance dose was 112.8g/kg per day. The dose was 226 times of clinical dosage and no death was found in mice. Conclusion: the toxicity of Kangxuan granules is very small and it can be considered safe in clinical use.

A wet/wet differential pressure sensor for measuring vertical hydraulic gradient.

PubMed

Fritz, Brad G; Mackley, Rob D

2010-01-01

Vertical hydraulic gradient is commonly measured in rivers, lakes, and streams for studies of groundwater-surface water interaction. While a number of methods with subtle differences have been applied, these methods can generally be separated into two categories; measuring surface water elevation and pressure in the subsurface separately or making direct measurements of the head difference with a manometer. Making separate head measurements allows for the use of electronic pressure sensors, providing large datasets that are particularly useful when the vertical hydraulic gradient fluctuates over time. On the other hand, using a manometer-based method provides an easier and more rapid measurement with a simpler computation to calculate the vertical hydraulic gradient. In this study, we evaluated a wet/wet differential pressure sensor for use in measuring vertical hydraulic gradient. This approach combines the advantage of high-temporal frequency measurements obtained with instrumented piezometers with the simplicity and reduced potential for human-induced error obtained with a manometer board method. Our results showed that the wet/wet differential pressure sensor provided results comparable to more traditional methods, making it an acceptable method for future use.

Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de

Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blotmore » analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a marker of cortical granules. • Active Rab3A triggered cortical granule exocytosis. • Blocking endogenous Rab3A inhibits cortical granule exocytosis. • Rab3A participates in cortical reaction in mouse oocytes.« less

Surface Localization of Zein Storage Proteins in Starch Granules from Maize Endosperm1

PubMed Central

Mu-Forster, Chen; Wasserman, Bruce P.

1998-01-01

Starch granules from maize (Zea mays) contain a characteristic group of polypeptides that are tightly associated with the starch matrix (C. Mu-Forster, R. Huang, J.R. Powers, R.W. Harriman, M. Knight, G.W. Singletary, P.L. Keeling, B.P. Wasserman [1996] Plant Physiol 111: 821–829). Zeins comprise about 50% of the granule-associated proteins, and in this study their spatial distribution within the starch granule was determined. Proteolysis of starch granules at subgelatinization temperatures using the thermophilic protease thermolysin led to selective removal of the zeins, whereas granule-associated proteins of 32 kD or above, including the waxy protein, starch synthase I, and starch-branching enzyme IIb, remained refractory to proteolysis. Granule-associated proteins from maize are therefore composed of two distinct classes, the surface-localized zeins of 10 to 27 kD and the granule-intrinsic proteins of 32 kD or higher. The origin of surface-localized δ-zein was probed by comparing δ-zein levels of starch granules obtained from homogenized whole endosperm with granules isolated from amyloplasts. Starch granules from amyloplasts contained markedly lower levels of δ-zein relative to granules prepared from whole endosperm, thus indicating that δ-zein adheres to granule surfaces after disruption of the amyloplast envelope. Cross-linking experiments show that the zeins are deposited on the granule surface as aggregates. In contrast, the granule-intrinsic proteins are prone to covalent modification, but do not form intermolecular cross-links. We conclude that individual granule intrinsic proteins exist as monomers and are not deposited in the form of multimeric clusters within the starch matrix. PMID:9536075

Insensitivity of compaction properties of brittle granules to size enlargement by roller compaction.

PubMed

Wu, Sy-Juen; Sun, Changquan 'Calvin'

2007-05-01

Pharmaceutical granules prepared by roller compaction often exhibit significant loss of tabletability, that is, reduction in tensile strength, when compared to virgin powder. This may be attributed to granule size enlargement for highly plastic materials, for example, microcrystalline cellulose. The sensitivity of powder compaction properties on granule size variations impacts the robustness of the dry granulation process. We hypothesize that such sensitivity of compaction properties on granule size is minimum for brittle materials because extensive fracture of brittle granules during compaction minimizes differences in initial granule size. We tested the hypothesis using three common brittle excipients. Results show that the fine (44-106 microm), medium (106-250 microm), and coarse (250-500 microm) granules exhibit essentially identical tabletability below a certain critical compaction pressure, 100, 140, and 100 MPa for spray-dried lactose monohydrate, anhydrous dibasic calcium phosphate, and mannitol, respectively. Above respective critical pressure, tabletability lines diverge with smaller granules exhibiting slightly higher tablet tensile strength at identical compaction conditions. Overall, tabletability of brittle granules is insensitive to granule size enlargement. The results provide a scientific basis to the common practice of incorporating brittle filler to a typical tablet formulation processed by roller compaction granulation. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

Roll compaction/dry granulation: comparison between roll mill and oscillating granulator in dry granulation.

PubMed

Sakwanichol, Jarunee; Puttipipatkhachorn, Satit; Ingenerf, Gernot; Kleinebudde, Peter

2012-01-01

Different experimental factorial designs were employed to evaluate granule properties obtained from oscillating granulator and roll mill. Four oscillating-granulator parameters were varied, i.e. rotor speed, oscillating angle, aperture of mesh screen and rotor type. Six roll-mill parameters that were throughput, speed ratio in both first and second stages, gap between roll pair in both stages and roll-surface texture were also investigated. Afterwards, the granule properties obtained from two milling types with similar median particle size were compared. All milling parameters in both milling types affected significantly the median particle size, size distribution and amount of fine particles (P < 0.05), except the rotor types of oscillating granulator on fines. Only three milling parameters influenced significantly the flowability (P < 0.05). These were the throughput and the gap size in the first stage of roll mill and the sieve size of oscillating granulator. In comparison between milling types, the differences of granule properties were not practically relevant. However, the roll mill had much higher capacity than the oscillating granulator about seven times, resulting in improving energy savings per unit of product. Consequently, the roll mill can be applied instead of oscillating granulator for roll compaction/dry granulation technique.

Asymmetrical Transmembrane Potential in Intracellular Organelles of Adrenal Chromatin Cells Exposed to Nanosecond Electric Pulses

NASA Astrophysics Data System (ADS)

Aramendia Zabaleta, Guillermo Jose

In our research on exploring the effects of 5 ns, high intensity electric pulses on neurosecretory adrenal chromaffin cells, cell modeling has played an important role in understanding and explaining the experimental results. Externally applied nanosecond-duration electric pulses (NEPs) can affect cells by creating nanopores in the cell and intracellular organelle membranes, making these membranes permeable to certain ions. A chromaffin cell contains, at a minimum, 7000 secretory granules plus other organelles such as mitochondria and the endoplasmic reticulum. In all the biological cell models constructed in the literature, there is no evidence of asymmetrical Transmembrane Potential (TMP) distribution in the intracellular membranes. However, these models do not include a realistic number of intracellular organelles. The goal of this research was to construct a more realistic cell model that incorporates a large number of secretory granules in the cytosol. To this end, a beta-version of the real-valued unstructured mesh Finite Element Method (FEM) electro-quasi-static module in Sim4life (SPEAG, Switzerland) has been used to model a chromaffin cell in which 1000 secretory granules are included in the cytosol. The model is, we believe, the most detailed geometrical cell model developed. It includes a spherical chromaffin cell (radius 8 mum), nucleus (radius 2.5 mum) located off-center, 500 granules (radius 200 nm) randomly located within a distance of 2 mum from the surface of the nucleus, and additional 500 granules randomly located in the remaining region of the cytosol. Cell and granule membrane thickness was set to 5 nm and nuclear membrane thickness to 10 nm. Dielectric properties of all constituents of the model were obtained from the literature or measured. Because the FEM Low Frequency solver is a quasi-static solver and not capable of accepting a time-varying pulse as input, all computations have been performed at single frequencies in the range DC to 60 MHz, sampled from the Fourier spectrum of the actual 5 ns pulse used in experiments. Electric field and TMP distributions have been computed in the cell model as a function of frequency, granule radius, and orientation of the applied E-field. Results show that granules located in the vicinity of the equatorial side of the nucleus had a higher TMP magnitude than the rest of the granules. In contrast, granules located in the vicinity of the poles of the nucleus had a lower TMP magnitude. The TMP distribution in the granules was strongly dependent on their location with respect to the nucleus and could exhibit asymmetries. Clearly, the nucleus had an influence on the TMP of the surrounding granules and the region of influence extended to a radial distance of 2 mu m from the nucleus. Creating a realistic model of a chromaffin cell is fundamental in order to estimate the TMP and electric field in a chromaffin cell. Such knowledge is important for understanding the impact of NEPs on the modulation of hormone secretion.

Effectiveness of wetting method for control of konzo and reduction of cyanide poisoning by removal of cyanogens from cassava flour.

PubMed

Banea, Jean Pierre; Bradbury, J Howard; Mandombi, Chretienne; Nahimana, Damien; Denton, Ian C; Kuwa, N'landa; Tshala Katumbay, D

2014-03-01

Konzo is an irreversible paralysis of the legs that occurs mainly among children and young women in remote villages in tropical Africa and is associated with a monotonous diet of bitter cassava. Konzo was discovered in 1938 by Dr. G. Trolli in the Democratic Republic of Congo (DRC). It also occurs in Mozambique, Tanzania, Cameroon, Central African Republic, and Angola. It was first controlled in Kay Kalenge village, DRC, in 2011 with the use of a wetting method to remove cyanogens from cassava flour. Fourteen months later, another visit was made to Kay Kalenge. To determine whether Kay Kalenge women were still using the wetting method, whether there were new cases of konzo, and whether the wetting method had spread to other villages. Meetings were held with chiefs, leaders, and heads of mothers' groups, women from 30 households were interviewed, and three nearby villages were visited. Total cyanide and thiocyanate were analyzed in cassava flour and urine samples, respectively. The women in Kay Kalenge village still used the wetting method. There were no new cases of konzo. The mean cyanide content of the flour samples was 9 ppm, and no child had a mean urinary thiocyanate content greater than 350 micromol/L. The use of the wetting method had spread naturally to three adjacent villages. The wetting method has been readily accepted by rural women as a simple and useful method to control konzo by removing cyanide from cassava flour, and its use has spread to nearby villages. The wetting method should be promoted by health authorities to control konzo and reduce cyanide poisoning from high-cyanide cassava flour.

Next-Generation Factory-Produced Cool Asphalt Shingles: Phase 1 Final Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levinson, Ronnen M.; Chen, Sharon S.; Ban-Weiss, George A.

As the least expensive category of high-slope roofing in the U.S., shingles are found on the roofs of about 80% of U.S. homes, and constitute about 80% (by product area) of this market. Shingles are also among the least reflective high-slope roofing products, with few cool options on the market. The widespread use of cool roofs in the two warmest U.S. climate zones could reduce annual residential cooling energy use in these zones by over 7%. This project targets the development of high-performance cool shingles with initial solar reflectance at least 0.40 and a cost premium not exceeding US$0.50/ft². Phasemore » 1 of the current study explored three approaches to increasing shingle reflectance. Method A replaces dark bare granules by white bare granules to enhance the near-infrared reflectance attained with cool pigments. Method B applies a white basecoat and a cool-color topcoat to a shingle surfaced with dark bare granules. Method C applies a visually clear, NIR-reflecting surface treatment to a conventionally colored shingle. Method A was the most successful, but our investigation of Method B identified roller coating as a promising top-coating technique, and our study of Method C developed a novel approach based on a nanowire mesh. Method A yielded red, green, brown, and black faux shingles with solar reflectance up to 0.39 with volumetric coloration. Since the base material is white, these reflectances can readily be increased by using less pigment. The expected cost premium for Method A shingles is less than our target limit of $0.50/ft², and would represent less than a 10% increase in the installed cost of a shingle roof. Using inexpensive but cool (spectrally selective) iron oxide pigments to volumetrically color white limestone synthesized from sequestered carbon and seawater appears to offer high albedo at low cost. In Phase 2, we plan to refine the cool shingle prototypes, manufacture cool granules, and manufacture and market high-performance cool shingles.« less

[Simultaneous determination of five main index components and specific chromatograms analysis in Xiaochaihu granules].

PubMed

Zhuang, Yan-Shuang; Cai, Hao; Liu, Xiao; Cai, Bao-Chang

2012-01-01

Reversed phase high performance liquid chromatography with diode array detector was employed for simultaneous determination of five main index components and specific chromatograms analysis in Xiaochaihu granules with a linear gradient elution of acetonitrile-water (containing 0.1% phosphoric acid) as mobile phase. The results showed that five main index components (baicalin, baicalein, wogonoside, wogonin, enoxolone) were separated well under the analytical condition. The linear ranges of five components were 0.518 - 16.576, 0.069 - 2.197, 0.167 - 5.333, 0.009 - 0.297 and 0.006 - 0.270 mg x g(-1), respectively. The correlation coefficients were 0.999 9, and the average recoveries ranged from 95% to 105%. Twelve common peaks were selected as the specific chromatograms of Xiaochaihu granules with baicalin as the reference peak. There were good similarities between the reference and the ten batches of samples. The similarity coefficients were no less than 0.9. The analytical method established is highly sensitive with strong specificity and it can be used efficiently in the quality control of Xiaochaihu granules.

[Multi-mathematical modelings for compatibility optimization of Jiangzhi granules].

PubMed

Yang, Ming; Zhang, Li; Ge, Yingli; Lu, Yanliu; Ji, Guang

2011-12-01

To investigate into the method of "multi activity index evaluation and combination optimized of mult-component" for Chinese herbal formulas. According to the scheme of uniform experimental design, efficacy experiment, multi index evaluation, least absolute shrinkage, selection operator (LASSO) modeling, evolutionary optimization algorithm, validation experiment, we optimized the combination of Jiangzhi granules based on the activity indexes of blood serum ALT, ALT, AST, TG, TC, HDL, LDL and TG level of liver tissues, ratio of liver tissue to body. Analytic hierarchy process (AHP) combining with criteria importance through intercriteria correlation (CRITIC) for multi activity index evaluation was more reasonable and objective, it reflected the information of activity index's order and objective sample data. LASSO algorithm modeling could accurately reflect the relationship between different combination of Jiangzhi granule and the activity comprehensive indexes. The optimized combination of Jiangzhi granule showed better values of the activity comprehensive indexed than the original formula after the validation experiment. AHP combining with CRITIC can be used for multi activity index evaluation and LASSO algorithm, it is suitable for combination optimized of Chinese herbal formulas.

Incomplete gastric metaplasia in children with insulin-dependent diabetes mellitus and celiac disease. An ultrastructural study

PubMed Central

Bertini, Marina; Sbarbati, Andrea; Valletta, Enrico; Pinelli, Leonardo; Tatò, Luciano

2001-01-01

Background The association of insulin-dependent diabetes mellitus (IDDM) and celiac disease (CD) has been widely reported in children but the relationship between the two conditions is incompletely understood. Moreover, specific studies on intestinal biopsies of patients with the association of the two diseases are still lacking. Methods We studied the ultrastructure of the duodenal mucosa in 12 patients with both IDDM and CD. Results All patients had either total or partial atrophy of duodenal mucosa. In seven subjects, an accumulation of electrondense granules in the apical cytoplasm of groups of enterocytes was found. In four of them, a double population of granules existed (mean diameter: 400-800 nm and 100-200 nm respectively) showing a biphasic pattern. In the other three patients, only smaller granules (100- 200 nm) were found in the enterocytes. Conclusions The present work suggests that patients with IDDM/CD may represent a subgroup in the context of the CD population. Intestinal biopsies of such individuals often show accumulation of electrondense granules in the apical cytoplasm of enterocytes that can be interpreted as incomplete gastric metaplasia. PMID:11466133

The biological significance of storage granules in rat parathyroid cells.

PubMed

Setoguti, T; Inoue, Y; Wild, P

1995-10-01

Both prosecretory and storage granules are concomitantly formed at the trans Golgi network including the innermost Golgi cisterna. Prosecretory granules develop into small secretory granules that release their contents by exocytosis finely regulated by a complex mechanism for maintaining calcium homeostasis. In the rat parathyroid cells, storage granules are large secretory granules storing parathyroid hormone for an emergency supply. The hormone is rapidly discharged by exocytosis when serum calcium concentration is decreased. The granules are constantly produced even under conditions of low serum calcium concentration in the regions of 8 mg/dl. The granule content is constantly hydrolyzed when not discharged, leading to a decreased core and finally to the formation of vacuolar bodies. The fate of the vacuolar bodies is unknown. Hypercalcemic conditions accelerate hydrolysis. The threshold value of calcium concentration required for the release of storage granule contents is between 8.0 and 7.5 mg/dl and that of calcium concentration for accelerating degradation of storage granules is about 11.5 mg/dl. Sympathetic stimulation causes storage granules to be discharged regardless of hypercalcemia or hypocalcemia. Parasympathetic stimulation accelerates hydrolysis. The degradation of storage granules seems to be closely associated with an intracellular regulatory mechanism for parathyroid hormone secretion.

Specific aerobic granules can be developed in a completely mixed tank reactor by bioaugmentation using micro-mycelial pellets of Phanerochaete chrysosporium.

PubMed

Hailei, Wang; Ping, Li; Qianlong, Jin; Ge, Qin

2014-03-01

Aerobic granules were firstly developed in a completely mixed tank reactor (CMTR) by seeding micro-mycelial pellets (MMPs) of Phanerochaete chrysosporium. During phenol wastewater treatment, sludge granulation rate reached 67 % after 15-day operation. The granules in CMTR are different from aerobic granules described in literature in morphology, and a majority of them are rod-shaped or rodlike sludge besides spherical granules. The polymorphic granules, having no essential difference with aerobic granules previously reported, achieve advantages over conventional activated sludge in settling ability, biomass concentration, density, integrity coefficient and removal ability to phenol wastewater. The optimized parameters for sludge granulation in CMTR including temperature, inoculum quantity, rotary speed and superficial air upflow velocity are 30 °C, 5–7 g/l, 150 rpm, and 0.5 cm/s, respectively. Analysis on sludge granulation mechanism indicates that MMPs not only result in the formation of aerobic granules containing MMPs as nuclei, but also induce the formation of biogranules which do not have MMP at their cores. The work challenges the general belief that the homogenous circular flow pattern of microbial aggregates is necessary for aerobic sludge granulation.

Calculating Soil Wetness, Evapotranspiration and Carbon Cycle Processes Over Large Grid Areas Using a New Scaling Technique

NASA Technical Reports Server (NTRS)

Sellers, Piers

2012-01-01

Soil wetness typically shows great spatial variability over the length scales of general circulation model (GCM) grid areas (approx 100 km ), and the functions relating evapotranspiration and photosynthetic rate to local-scale (approx 1 m) soil wetness are highly non-linear. Soil respiration is also highly dependent on very small-scale variations in soil wetness. We therefore expect significant inaccuracies whenever we insert a single grid area-average soil wetness value into a function to calculate any of these rates for the grid area. For the particular case of evapotranspiration., this method - use of a grid-averaged soil wetness value - can also provoke severe oscillations in the evapotranspiration rate and soil wetness under some conditions. A method is presented whereby the probability distribution timction(pdf) for soil wetness within a grid area is represented by binning. and numerical integration of the binned pdf is performed to provide a spatially-integrated wetness stress term for the whole grid area, which then permits calculation of grid area fluxes in a single operation. The method is very accurate when 10 or more bins are used, can deal realistically with spatially variable precipitation, conserves moisture exactly and allows for precise modification of the soil wetness pdf after every time step. The method could also be applied to other ecological problems where small-scale processes must be area-integrated, or upscaled, to estimate fluxes over large areas, for example in treatments of the terrestrial carbon budget or trace gas generation.

PHB granules are attached to the nucleoid via PhaM in Ralstonia eutropha

PubMed Central

2012-01-01

Background Poly(3-hydroxybutyrate) (PHB) granules are important storage compounds of carbon and energy in many prokaryotes which allow survival of the cells in the absence of suitable carbon sources. Formation and subcellular localization of PHB granules was previously assumed to occur randomly in the cytoplasm of PHB accumulating bacteria. However, contradictionary results on subcellular localization of PHB granules in Ralstonia eutropha were published, recently. Results Here, we provide evidence by transmission electron microscopy that PHB granules are localized in close contact to the nucleoid region in R. eutropha during growth on nutrient broth. Binding of PHB granules to the nucleoid is mediated by PhaM, a PHB granule associated protein with phasin-like properties that is also able to bind to DNA and to phasin PhaP5. Over-expression of PhaM resulted in formation of many small PHB granules that were always attached to the nucleoid region. In contrast, PHB granules of ∆phaM strains became very large and distribution of granules to daughter cells was impaired. Association of PHB granules to the nucleoid region was prevented by over-expression of PhaP5 and clusters of several PHB granules were mainly localized near the cell poles. Conclusion Subcellular localization of PHB granules is controlled in R. eutropha and depends on the presence and concentrations of at least two PHB granule associated proteins, PhaM and PhaP5. PMID:23157596

Lithium granule ablation and penetration during ELM pacing experiments at DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunsford, R.; Bortolon, A.; Roquemore, A. L.

At DIII-D, lithium granules were radially injected into the plasma at the outer midplane to trigger and pace edge localized modes (ELMs). Granules ranging in size from 300 to 1000 microns were horizontally launched into H-mode discharges with velocities near 100 m/s, and granule to granule injection frequencies less than 500 Hz. While the smaller granules were only successful in triggering ELMs approximately 20% of the time, the larger granules regularly demonstrated ELM triggering efficiencies of greater than 80%. A fast visible camera looking along the axis of injection observed the ablation of the lithium granules. We used the durationmore » of ablation as a benchmark for a neutral gas shielding calculation, and approximated the ablation rate and mass deposition location for the various size granules, using measured edge plasma profiles as inputs. In conclusion, this calculation suggests that the low triggering efficiency of the smaller granules is due to the inability of these granules to traverse the steep edge pressure gradient region and reach the top of the pedestal prior to full ablation.« less

Lithium granule ablation and penetration during ELM pacing experiments at DIII-D

DOE PAGES

Lunsford, R.; Bortolon, A.; Roquemore, A. L.; ...

2016-05-25

At DIII-D, lithium granules were radially injected into the plasma at the outer midplane to trigger and pace edge localized modes (ELMs). Granules ranging in size from 300 to 1000 microns were horizontally launched into H-mode discharges with velocities near 100 m/s, and granule to granule injection frequencies less than 500 Hz. While the smaller granules were only successful in triggering ELMs approximately 20% of the time, the larger granules regularly demonstrated ELM triggering efficiencies of greater than 80%. A fast visible camera looking along the axis of injection observed the ablation of the lithium granules. We used the durationmore » of ablation as a benchmark for a neutral gas shielding calculation, and approximated the ablation rate and mass deposition location for the various size granules, using measured edge plasma profiles as inputs. In conclusion, this calculation suggests that the low triggering efficiency of the smaller granules is due to the inability of these granules to traverse the steep edge pressure gradient region and reach the top of the pedestal prior to full ablation.« less

Simulation of roller compaction with subsequent tableting and characterization of lactose and microcrystalline cellulose.

PubMed

Hein, Stephanie; Picker-Freyer, Katharina M; Langridge, John

2008-01-01

Tablets are by far the most common solid oral dosage forms, and many drugs need to be granulated before they can be tableted. Increasingly roller compaction is being used as a dry granulation technique; however it is a very time and material intensive method. Thus some mini roller compactors and simulations of the roller compaction process have been developed as a means of studying the technique at small scale. An important factor in the selection of materials for roller compaction is their ability to be recompressed into tablets after the initial roller compaction and milling steps. In this paper the roller compaction process was simulated on the basis of some models by Gereg and Cappola (2002) and Zinchuk et al. (2004). An eccentric tableting machine was used to make compacts from alpha-lactose monohydrate, anhydrous beta-lactose, spray-dried lactose and microcrystalline cellulose at different maximum relative densities (rho rel,max 0.6-0.9). These compacts were milled immediately to granules with a rotary granulator. The properties of the granules were analyzed and compared to the properties of the original powders. These granules and powders were then tableted at different maximum relative densities (rho rel,max 0.75-0.95) and their properties including elastic recovery, crushing force and 3D-model were analyzed. The properties of the tablets made from the granules were compared to the properties of the tablets made from the powders to determine which excipients are most suitable for the roller compaction process. The study showed that anhydrous beta-lactose is the preferred form of lactose for use in roller compaction since compaction did not affect tablet crushing force to a large extent. With the simulation of roller compaction process one is able to find qualified materials for use in roller compaction without the necessity of a great deal of material and time.

Osseointegration of alumina bioceramic granules: A comparative experimental study

NASA Astrophysics Data System (ADS)

Rerikh, V. V.; Avetisyan, A. R.; Zaydman, A. M.; Anikin, K. A.; Bataev, V. A.; Nikulina, A. A.; Sadovoy, M. A.; Aronov, A. M.; Semantsova, E. S.

2016-08-01

To perform a comparative analysis of osseointegration of bioceramic alumina-based granules, hydroxyapatite-based granules, and deproteinized bone granules. The experiment was conducted on 52 adult male Kyoto-Wistar rats weighing 350 to 520 g. The animals were divided into five matched groups that differed only in the type of an implanted material. The granules were implanted in the lumbar vertebral bodies and in the distal right femur of each laboratory animal. Two months after surgery, the animals were euthanized, followed by tissue sampling for morphological studies. An examination of specimens from the groups with implanted alumina granules revealed the newly formed trabecular bone with remodeling signs. The bone tissue filled the intragranular space, tightly adhering to the granule surface. There was no connective tissue capsule on the border between bone tissue and alumina granules. Cylindrical bioceramic alumina-based granules with an open internal channel have a higher strength surpassing than that of analogs and the osseointegration ability close to that of hydroxyapatite and deproteinized bone granules.

Spinosad as an effective larvicide for control of Aedes albopictus and Aedes aegypti, vectors of dengue in southern Mexico.

PubMed

Marina, Carlos F; Bond, J Guillermo; Casas, Mauricio; Muñoz, José; Orozco, Arnoldo; Valle, Javier; Williams, Trevor

2011-01-01

Field trials were conducted during the wet and dry seasons in periurban and semi-rural cemeteries in southern Mexico to determine the efficacy of a suspension concentrate formulation of spinosad (Tracer 480SC) on the inhibition of development of Aedes albopictus L. and Ae. aegypti Skuse. For this, oviposition traps were treated with spinosad (1 or 5 mg L(-1)), Bacillus thuringiensis israelensis (Bti, VectoBac 12AS), a sustained release formulation of temephos and a water control. Ae. albopictus was subordinate to Ae. aegypti during the dry season, but became dominant or codominant during the wet season at both sites. The two species could not be differentiated in field counts on oviposition traps. Mean numbers of larvae + pupae of Aedes spp. in Bti-treated containers were similar to the control at both sites during both seasons. The duration of complete absence of aquatic stages varied from 5 to 13 weeks for the spinosad treatments and from 6 to 9 weeks for the temephos treatment, depending on site, season and product concentration. Predatory Toxorhynchites theobaldi Dyar and Knab suffered low mortality in control and Bti treatments, but high mortality in spinosad and temephos treatments. Egg counts and percentage of egg hatch of Aedes spp. increased significantly between the dry and wet seasons, but significant treatment differences were not detected. Temephos granules and a suspension concentrate formulation of spinosad were both highly effective larvicides against Ae. aegypti and Ae. albopictus. These compounds merit detailed evaluation for inclusion in integrated control programs targeted at Ae. aegypti and Ae. albopictus in regions where they represent important vectors of human diseases. Copyright © 2010 Society of Chemical Industry.

[Simultaneous determination of ephedrine hydrochloride, D-pseudoephedrine and amygdalin in xiao'er pingchuan qutan granule by HPLC].

PubMed

Yang, De-Bin; Tong, Yan; Ma, Zhen-Shan; Wang, Lin; Dong, Mei-Hong; Li, Yan-Ling; Wang, Jin-Yu

2013-03-01

To establish an HPLC method for the determination of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule. Pheny ether chromatographic column (4.6 mm x 250 mm, 5 microm) was adopted, with acetonitrile-0.1% phosphoric acid (containing 0.1% three ethylamine) (3:97) as the mobile phase. The UV detection wavelength was at 210 nm, with the flow rate of 1 mL x min(-1), and column temperature was at 35 degrees C. The linearity of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin ranged between 0.078 60-3.144 microg (r = 1.000 0), 0.103 4-2.068 microg (r = 0.999 7) and 0.430 5-3.157 microg (r = 0.999 8), respectively. Their average recoveries were 98.46% (RSD 1.1%), 103.0% (RSD 1.5%) and 97.15% (RSD 2.1%), respectively. The method is simple, stable and reliable that it can be used to determine the content of ephedrine hydrochloride, D-pseudo-ephedrine and amygdalin in Xiao'er Pingchuan Qutan granule.

Wound healing activity of Persea americana (avocado) fruit: a preclinical study on rats.

PubMed

Nayak, B S; Raju, S S; Chalapathi Rao, A V

2008-03-01

Avocado (Persea americana) oil is rich in nutrient waxes, proteins and minerals, as well as vitamins A, D and E. It is an excellent source of enrichment for dry, damaged or chapped skin. This study aimed to evaluate the wound-healing activity of fruit extract of Persea americana in rats. The effect of topical and oral administration of Persea americana fruit extract (300 mg/kg/day) on excision and dead space wound models was evaluated. The rats used in the excision wound model were divided into four groups of five each and received either topical or oral treatment. The rats used in the dead space wound model were divided into two groups of five each and were treated orally. Healing was assessed by the rate of wound contraction, period of epithelialisation, granulation tissue weight and hydoxyproline content. In the excision wound model, complete healing (full epithelialisation) was observed on average on day 14 in the rats who receive oral or topical treatment. In contrast, the controls took approximately 17 days to heal completely. The extract-treated wounds were found to epithelialise faster than the controls (p < 0.001). Wet and dry granulation tissue weight and the hydroxyproline content of the tissue obtained from extract-treated animals used in the dead space wound model were significantly higher (p < 0.05) compared with the controls. Rate of wound contraction, epithelialisation time together with the hydroxyproline content and histological observations support the use of Persea americana in the management of wound healing.

Effects of Hibiscus rosa sinensis L (Malvaceae) on wound healing activity: a preclinical study in a Sprague Dawley rat.

PubMed

Shivananda Nayak, B; Sivachandra Raju, S; Orette, F A; Chalapathi Rao, A V

2007-06-01

Hibiscus rosa sinensis (H rosa sinensis), a plant product, has been used for the treatment of a variety of diseases as well as to promote wound healing. The wound-healing activity of the ethanol extract of H rosa sinensis flower was determined in rats, using excision, incision, and dead space wound models and is presented in this report. The animals were randomly divided into 2 groups of 6 each in all the models. Test group animals in each model were treated with the ethanol extract of H rosa sinensis orally by mixing in drinking water (120 mg kg(-1) day(-1)), and the control group animals were maintained with plain drinking water. Healing was assessed by the rate of wound contraction, period of epithelialization, tensile strength (skin breaking strength), granulation tissue weight, and hydroxyproline content. The antimicrobial activity of the flower extract against selected microorganisms that infect the wounds was also assessed. Animals treated with the extract exhibited an 86% reduction in the wound area compared with controls, who exhibited a 75% reduction. The extract-treated animals were found to epithelize their wounds significantly faster than controls (P < .002) and have shown significantly higher skin-breaking strength than controls (P < .002). The dry and wet weight of granulation tissue and hydroxyproline content were also increased significantly when compared with controls. The reported observations suggest H rosa sinensis aids wound healing in the rat model.

Dehydration and Stabilization of a Reactive Tertiary Hydroxyl Group in Solid Oral Dosage Forms of BMS-779788.

PubMed

Adams, Monica L; Sharma, Vijayata; Gokhale, Madhushree; Huang, Yande; Stefanski, Kevin; Su, Ching; Hussain, Munir A

2016-04-01

BMS-779788 contains a reactive tertiary hydroxyl attached to a weakly basic imidazole ring. Propensity of the carbinol toward dehydration to yield the corresponding alkene, BMS-779788-ALK, was evaluated. Elevated levels of BMS-779788-ALK were observed in excipient compatibility samples. Stability studies revealed that BMS-779788 degrades to BMS-779788-ALK in capsules and tablets prepared by both dry and wet granulation processes. An acid-catalyzed dehydration mechanism, in which the heterocyclic core contributes resonance stability to the cationic intermediate via charge transfer to the imidazole ring, was proposed. Therefore, neutralization via a buffered (pH 7.0) granulating solution was used to mitigate dehydration. Solution studies revealed degradation of BMS-779788 to BMS-779788-ALK over the pH range of 1-7.5. Reversibility was confirmed by initiating reactions with BMS-779788-ALK over the same pH range. Accordingly, a simple reversible scheme can be used to describe reactions initiated with either BMS-779788 or BMS-779788-ALK. To eliminate potential for charge delocalization across the heterocycle and probe the degradation mechanism, the imidazole ring of BMS-779788 was methylated (BMS-779788-Me). The propensity for acid-catalyzed dehydration was then evaluated. The acid stability of BMS-779788-Me confirmed that the heterocyclic core contributes to reactivity liability of the tertiary hydroxyl. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Formation of artificial granules for proving gelation as the main mechanism of aerobic granulation in biological wastewater treatment.

PubMed

Li, Yun; Yang, Shu-Fang; Zhang, Jian-Jun; Li, Xiao-Yan

2014-01-01

In this study, gelation-facilitated biofilm formation as a new mechanism is proposed for the phenomenon of aerobic granulation in biological wastewater treatment. To obtain an experimental proof for the gelation-based theory, the granulation process was simulated in a chemical system using latex particles for bacterial cells and organic polymers (alginate and peptone) for extracellular polymeric substances (EPS) in a solution with the addition of cations (Ca²⁺, Mg²⁺ and Fe³⁺). The results showed that at a low alginate content (70 mg g⁻¹ mixed liquid suspended solids (MLSS)) flocculation was observed in the suspension with loose flocs. At a higher alginate content (180 mg g⁻¹ MLSS), together with discharge of small flocs, formation of artificial gel granules was successfully achieved leading to granulation. The artificial granules show a morphological property similar to that of actual microbial granules. However, if the protein content increased, granulation became difficult with little gel formation. The experimental work demonstrates the importance of the bonding interactions between EPS functional groups and cations in gel formation and granulation. The laboratory results on the formation of artificial granules provide a sound proof for the theory of gelation-facilitated biofilm formation as the main mechanism for aerobic granulation in sludge suspensions.

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets.

PubMed

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH's intrinsic characteristics.

The Preparation of Capsaicin-Chitosan Microspheres (CCMS) Enteric Coated Tablets

PubMed Central

Chen, Jian; Huang, Gui-Dong; Tan, Si-Rong; Guo, Jiao; Su, Zheng-Quan

2013-01-01

This study aimed to research the preparation and content determination of capsaicin-chitosan microspheres (CCMS) enteric coated tablets. The core tablets were prepared with the method of wet granulation. Nine formulae were designed to determine the optimal formula of the core tablet. Eudragit L100 was used to prepare the CCMS enteric-coated tablets. The effect of enteric coated formulation variables such as content of talc (10%, 25% and 40%), plasticisers (TEC and DBS), dosage of plasticiser (10%, 20% and 30%) and coating weight (2%, 3% and 5%) were evaluated for drug release characteristics. The in vitro release was studied using 0.1 N HCl and pH 6.8 phosphate buffer. Enteric coated tablets without ruptures or swelling behaviour over 2 h in 0.1 N HCl indicated that these tablets showed acid resistance. The accumulated release rate in phosphate buffer (pH 6.8) revealed that the prepared tablets were able to sustain drug release into the intestine and a first-order release was obtained for capsaicin. This research is the first report of the preparation and content determination of CCMS enteric coated tablets. The sustained release behavior of enteric coated formulations in pH 6.8 phosphate buffer demonstrated that it would be a potential drug delivery platform for sustained delivery of gastric irritant drugs. PMID:24351818

A novel spray-dried nanoparticles-in-microparticles system for formulating scopolamine hydrobromide into orally disintegrating tablets

PubMed Central

Li, Feng-Qian; Yan, Cheng; Bi, Juan; Lv, Wei-Lin; Ji, Rui-Rui; Chen, Xu; Su, Jia-Can; Hu, Jin-Hong

2011-01-01

Scopolamine hydrobromide (SH)-loaded microparticles were prepared from a colloidal fluid containing ionotropic-gelated chitosan nanoparticles using a spray-drying method. The spray-dried microparticles were then formulated into orally disintegrating tablets (ODTs) using a wet granulation tablet formation process. A drug entrapment efficiency of about 90% (w/w) and loading capacity of 20% (w/w) were achieved for the microparticles, which ranged from 2 μm to 8 μm in diameter. Results of disintegration tests showed that the formulated ODTs could be completely dissolved within 45 seconds. Drug dissolution profiles suggested that SH is released more slowly from tablets made using the microencapsulation process compared with tablets containing SH that is free or in the form of nanoparticles. The time it took for 90% of the drug to be released increased significantly from 3 minutes for conventional ODTs to 90 minutes for ODTs with crosslinked microparticles. Compared with ODTs made with noncrosslinked microparticles, it was thus possible to achieve an even lower drug release rate using tablets with appropriate chitosan crosslinking. Results obtained indicate that the development of new ODTs designed with crosslinked microparticles might be a rational way to overcome the unwanted taste of conventional ODTs and the side effects related to SH’s intrinsic characteristics. PMID:21720502

Quality-by-design approach for the development of telmisartan potassium tablets.

PubMed

Oh, Ga-Hui; Park, Jin-Hyun; Shin, Hye-Won; Kim, Joo-Eun; Park, Young-Joon

2018-05-01

A quality-by-design approach was adopted to develop telmisartan potassium (TP) tablets, which were bioequivalent with the commercially available Micardis ® (telmisartan free base) tablets. The dissolution pattern and impurity profile of TP tablets differed from those of Micardis ® tablets because telmisartan free base is poorly soluble in water. After identifying the quality target product profile and critical quality attributes (CQAs), drug dissolution, and impurities were predicted to be risky CQAs. To determine the exact range and cause of risks, we used the risk assessment (RA) tools, preliminary hazard analysis and failure mode and effect analysis to determine the parameters affecting drug dissolution, impurities, and formulation. The range of the design space was optimized using the face-centered central composite design among the design of experiment (DOE) methods. The binder, disintegrant, and kneading time in the wet granulation were identified as X values affecting Y values (disintegration, hardness, friability, dissolution, and impurities). After determining the design space with the desired Y values, the TP tablets were formulated and their dissolution pattern was compared with that of the reference tablet. The selected TP tablet formulated using design space showed a similar dissolution to that of Micardis ® tablets at pH 7.5. The QbD approach TP tablet was bioequivalent to Micardis ® tablets in beagle dogs.

Influence of beta-cyclodextrin and chitosan in the formulation of a colon-specific drug delivery system.

PubMed

Rehman, K; Amin, M C I M; Muda, S

2013-12-01

The increase in diseases of the colon underscores the need to develop cost-effective site-directed therapies. We formulated a polysaccharide-based matrix system that could release ibuprofen under conditions simulating those in the colon by employing a wet granulation method. Tablets were prepared in a series of formulations containing a polysaccharide (beta-cyclodextrin and chitosan) matrix system along with ethylcellulose. We characterized physicochemical properties and performed an in vitro drug release assay in the absence and presence of digestive enzymes to assess the ability of the polysaccharides to function as a protective barrier against the upper gastrointestinal environment. Fourier transform infrared spectroscopy studies revealed no chemical interaction between ibuprofen and polysaccharides; however, spectrum analysis suggested the formation of an inclusion complex of beta-cyclodextrin with ibuprofen. The formulations contained 50% ethylcellulose and 50% beta-cyclodextrins (1:1) were proven to be the better formulation that slowly released the drug until 24 h (101.04 ± 0.65% maximum drug release in which 83.08 ± 0.89% drug was released in colonic medium) showed better drug release profiles than the formulations containing chitosan. We conclude that a beta-cyclodextrin drug carrier system may represent an effective approach for treatment of diseases of the colon. © Georg Thieme Verlag KG Stuttgart · New York.

Colon targeted curcumin delivery using guar gum.

PubMed

Elias, Edwin J; Anil, Singhal; Ahmad, Showkat; Daud, Anwar

2010-06-01

Curcumin is used in the treatment of colon cancer, but its very poor absorption in the upper part of the GIT is a major concern. As a site for drug delivery, the colon offers a near neutral pH, reduced digestive enzymatic activity, a long transit time and an increased responsiveness to absorption enhancers. The aim of the present study was to identify a suitable polymer (guar gum) based matrix tablet for curcumin with sufficient mechanical strength and promising in vitro mouth-to-colon release profile. Three formulations of curcumin were prepared using varying concentrations of guar gum containing 50 mg curcumin by the wet granulation method. Tablets were subjected to evaluation by studying parameter like hardness, friability, drug content uniformity, and in-vitro drug release. In vitro drug release was evaluated using simulated stomach, intestinal and colonic fluids. The susceptibility of guar gum to colonic bacteria was also assessed by a drug release study with rat caecal contents. The 40% guar gum containing formulation (F-1) showed better drug release (91.1%) after 24 hours in the presence of rat caecal contents in comparison with the 50% guar gum containing formulation (F-2) (82.1%). Curcumin could, thus, be positively delivered to the colon for effective colon cancer treatment using guar gum.

Granule Formation Mechanisms within an Aerobic Wastewater System for Phosphorus Removal▿ †

PubMed Central

Barr, Jeremy J.; Cook, Andrew E.; Bond, Phillip L.

2010-01-01

Granular sludge is a novel alternative for the treatment of wastewater and offers numerous operational and economic advantages over conventional floccular-sludge systems. The majority of research on granular sludge has focused on optimization of engineering aspects relating to reactor operation with little emphasis on the fundamental microbiology. In this study, we hypothesize two novel mechanisms for granule formation as observed in three laboratory scale sequencing batch reactors operating for biological phosphorus removal and treating two different types of wastewater. During the initial stages of granulation, two distinct granule types (white and yellow) were distinguished within the mixed microbial population. White granules appeared as compact, smooth, dense aggregates dominated by 97.5% “Candidatus Accumulibacter phosphatis,” and yellow granules appeared as loose, rough, irregular aggregates with a mixed microbial population of 12.3% “Candidatus Accumulibacter phosphatis” and 57.9% “Candidatus Competibacter phosphatis,” among other bacteria. Microscopy showed white granules as homogeneous microbial aggregates and yellow granules as segregated, microcolony-like aggregates, with phylogenetic analysis suggesting that the granule types are likely not a result of strain-associated differences. The microbial community composition and arrangement suggest different formation mechanisms occur for each granule type. White granules are hypothesized to form by outgrowth from a single microcolony into a granule dominated by one bacterial type, while yellow granules are hypothesized to form via multiple microcolony aggregation into a microcolony-segregated granule with a mixed microbial population. Further understanding and application of these mechanisms and the associated microbial ecology may provide conceptual information benefiting start-up procedures for full-scale granular-sludge reactors. PMID:20851963

State of the art of aerobic granulation in continuous flow bioreactors.

PubMed

Kent, Timothy R; Bott, Charles B; Wang, Zhi-Wu

In the wake of the success of aerobic granulation in sequential batch reactors (SBRs) for treating wastewater, attention is beginning to turn to continuous flow applications. This is a necessary step given the advantages of continuous flow treatment processes and the fact that the majority of full-scale wastewater treatment plants across the world are operated with aeration tanks and clarifiers in a continuous flow mode. As in SBRs, applying a selection pressure, based on differences in either settling velocity or the size of the biomass, is essential for successful granulation in continuous flow reactors (CFRs). CFRs employed for aerobic granulation come in multiple configurations, each with their own means of achieving such a selection pressure. Other factors, such as bioaugmentation and hydraulic shear force, also contribute to aerobic granulation to some extent. Besides the formation of aerobic granules, long-term stability of aerobic granules is also a critical issue to be addressed. Inorganic precipitation, special inocula, and various operational optimization strategies have been used to improve granule long-term structural integrity. Accumulated studies reviewed in this work demonstrate that aerobic granulation in CFRs is capable of removing a wide spectrum of contaminants and achieving properties generally comparable to those in SBRs. Despite the notable research progress made toward successful aerobic granulation in lab-scale CFRs, to the best of our knowledge, there are only three full-scale tests of the technique, two being seeded with anammox-supported aerobic granules and the other with conventional aerobic granules; two other process alternatives are currently in development. Application of settling- or size-based selection pressures and feast/famine conditions are especially difficult to implement to these and similar mainstream systems. Future research efforts needs to be focused on the optimization of the granule-to-floc ratio, enhancement of granule activity, improvement of long-term granule stability, and a better understanding of aerobic granulation mechanisms in CFRs, especially in full-scale applications. Copyright © 2018 Elsevier Inc. All rights reserved.

Granulation of fine powder

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Ching-Fong

A mixture of fine powder including thorium oxide was converted to granulated powder by forming a first-green-body and heat treating the first-green-body at a high temperature to strengthen the first-green-body followed by granulation by crushing or milling the heat-treated first-green-body. The granulated powder was achieved by screening through a combination of sieves to achieve the desired granule size distribution. The granulated powder relies on the thermal bonding to maintain its shape and structure. The granulated powder contains no organic binder and can be stored in a radioactive or other extreme environment. The granulated powder was pressed and sintered to formmore » a dense compact with a higher density and more uniform pore size distribution.« less

Characteristics of aerobic granules grown on glucose and acetate in sequential aerobic sludge blanket reactors.

PubMed

Tay, J H; Liu, Q S; Liu, Y

2002-08-01

Aerobic granules were cultivated in two column-type sequential aerobic sludge blanket reactors fed with glucose and acetate, respectively. The characteristics of aerobic granules were investigated. Results indicated that the glucose- and acetate-fed granules have comparable characteristics in terms of settling velocity, size, shape, biomass density, hydrophobicity, physical strength, microbial activity and storage stability. Substrate component does not seem to be a key factor on the formation of aerobic granules. However, microbial diversity of the granules is closely associated with the carbon sources supplied to the reactors. Compared with the conventional activated sludge flocs, aerobic granules exhibit excellent physical characteristics that would be essential for industrial application. This research provides a complete set of characteristics data of aerobic granules grown on glucose and acetate, which would be useful for further development of aerobic granules-based compact bioreactor for handling high strength organic wastewater.

Starch-Branching Enzymes Preferentially Associated with A-Type Starch Granules in Wheat Endosperm1

PubMed Central

Peng, Mingsheng; Gao, Ming; Båga, Monica; Hucl, Pierre; Chibbar, Ravindra N.

2000-01-01

Two starch granule-bound proteins (SGP), SGP-140 and SGP-145, were preferentially associated with A-type starch granules (>10 μm) in developing and mature wheat (Triticum aestivum) kernels. Immunoblotting and N-terminal sequencing suggested that the two proteins were different variants of SBEIc, a 152-kD isoform of wheat starch-branching enzyme. Both SGP-140 and SGP-145 were localized to the endosperm starch granules but were not found in the endosperm soluble fraction or pericarp starch granules younger than 15 d post anthesis (DPA). Small-size starch granules (<10 μm) initiated before 15 DPA incorporated SGP-140 and SGP-145 throughout endosperm development and grew into full-size A-type starch granules (>10 μm). In contrast, small-size starch granules harvested after 15 DPA contained only low amounts of SGP-140 and SGP-145 and developed mainly into B-type starch granules (<10 μm). Polypeptides of similar mass and immunologically related to SGP-140 and/or SGP-145 were also preferentially incorporated into A-type starch granules of barley (Hordeum vulgare), rye (Secale cereale), and triticale (× Triticosecale Wittmack) endosperm, which like wheat endosperm have a bimodal starch granule size distribution. PMID:10982441

Comparison of waxy and normal potato starch remaining granules after chemical surface gelatinization: pasting behavior and surface morphology.

PubMed

Huang, Junrong; Chen, Zhenghong; Xu, Yalun; Li, Hongliang; Liu, Shuxing; Yang, Daqing; Schols, Henk A

2014-02-15

To understand the contribution of granule inner portion to the pasting property of starch, waxy potato starch and two normal potato starches and their acetylated starch samples were subjected to chemical surface gelatinization by 3.8 mol/L CaCl2 to obtain remaining granules. Native and acetylated, original and remaining granules of waxy potato starch had similar rapid visco analyzer (RVA) pasting profiles, while those of two normal potato starches behaved obviously different from each other. All remaining granules had lower peak viscosity than the corresponding original granules. Contribution of waxy potato starch granule's inner portion to the peak viscosity was significant more than those of normal potato starches. The shell structure appearing on the remaining granule surface for waxy potato starch was smoother and thinner than that for normal potato starches as observed by scanning electron microscopy, indicating a more regular structure of shell and a more ordered packing of shell for waxy potato starch granules. The blocklet size of waxy potato starch was smaller and more uniform than those of normal potato starches as shown by atomic force microscopy images of original and remaining granules. In general, our results provided the evidence for the spatial structure diversity between waxy and normal potato starch granules: outer layer and inner portion of waxy potato starch granule had similar structure, while outer layer had notably different structure from inner portion for normal potato starch granule. Copyright © 2013 Elsevier Ltd. All rights reserved.

PREPARATION OF HIGH-DENSITY THORIUM OXIDE SPHERES

DOEpatents

McNees, R.A. Jr.; Taylor, A.J.

1963-12-31

A method of preparing high-density thorium oxide spheres for use in pellet beds in nuclear reactors is presented. Sinterable thorium oxide is first converted to free-flowing granules by means such as compression into a compact and comminution of the compact. The granules are then compressed into cubes having a density of 5.0 to 5.3 grams per cubic centimeter. The cubes are tumbled to form spheres by attrition, and the spheres are then fired at 1250 to 1350 deg C. The fired spheres are then polished and fired at a temperature above 1650 deg C to obtain high density. Spherical pellets produced by this method are highly resistant to mechanical attrition hy water. (AEC)

Monitoring of exocytosis and endocytosis of insulin secretory granules in the pancreatic beta-cell line MIN6 using pH-sensitive green fluorescent protein (pHluorin) and confocal laser microscopy.

PubMed

Ohara-Imaizumi, Mica; Nakamichi, Yoko; Tanaka, Toshiaki; Katsuta, Hidenori; Ishida, Hitoshi; Nagamatsu, Shinya

2002-04-01

The dynamics of exocytosis/endocytosis of insulin secretory granules in pancreatic beta-cells remains to be clarified. In the present study, we visualized and analysed the motion of insulin secretory granules in MIN6 cells using pH-sensitive green fluorescent protein (pHluorin) fused to either insulin or the vesicle membrane protein, phogrin. In order to monitor insulin exocytosis, pHluorin, which is brightly fluorescent at approximately pH 7.4, but not at approximately pH 5.0, was attached to the C-terminus of insulin. To monitor the motion of insulin secretory granules throughout exocytosis/endocytosis, pHluorin was inserted between the third and fourth amino acids after the identified signal-peptide cleavage site of rat phogrin cDNA. Using this method of cDNA construction, pHluorin was located in the vesicle lumen, which may enable discrimination of the unfused acidic secretory granules from the fused neutralized ones. In MIN6 cells expressing insulin-pHluorin, time-lapse confocal laser scanning microscopy (5 or 10 s intervals) revealed the appearance of fluorescent spots by depolarization after stimulation with 50 mM KCl and 22 mM glucose. The number of these spots in the image at the indicated times was counted and found to be consistent with the results of insulin release measured by RIA during the time course. In MIN6 cells expressing phogrin-pHluorin, data showed that fluorescent spots appeared following high KCl stimulation and remained stationary for a while, moved on the plasma membrane and then disappeared. Thus we demonstrate the visualized motion of insulin granule exocytosis/endocytosis using the pH-sensitive marker, pHluorin.

High-dose-rate (HDR) brachytherapy for the treatment of benign obstructive endobronchial granulation tissue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madu, Chika N.; Machuzak, Michael S.; Sterman, Daniel H.

Background: Severe airway obstruction can occur in the setting of benign granulation tissue forming at bronchial anastomotic sites after lung transplantation in up to 20% of patients. Many of these benign lesions respond to stent placement, laser ablation, or balloon bronchoplasty. However, in certain cases, proliferation of granulation tissue may persist despite all therapeutic attempts. This study describes a series of refractory patients treated with high-dose-rate (HDR) brachytherapy for benign proliferation of granulation tissue, causing airway compromise. Methods and Materials: Between April 2002 and June 2005, 5 patients with significant airway compromise from recurrent granulation tissue were treated with HDRmore » brachytherapy. All patients had previously failed to maintain a patent airway despite multiple bronchoscopic interventions. Treatment was delivered using an HDR brachytherapy afterloader with {sup 192}Ir. Dose prescription was to a depth of 1 cm. All patients were treated weekly, with total doses ranging from 10 Gy to 21 Gy in two to three fractions. Results: The median follow-up was 12 months. All patients experienced a reduction in therapeutic bronchoscopic procedures after HDR brachytherapy compared with the pretreatment period. With the exception of possible radiation-induced bronchitis in 1 patient, there were no other treatment related complications. At the time of this report, 2 patients have died and the other 3 are alive with marked symptomatic improvement and reduced bronchoscopic procedures. Conclusion: High-dose-rate brachytherapy is an effective treatment for benign proliferation of granulation tissue causing airway obstruction. The early response to therapy is encouraging and further follow-up is necessary to determine long-term durability and late effects.« less

Method of fabricating metal- and ceramic- matrix composites and functionalized textiles

DOEpatents

Maxwell, James L [Jemez Springs, NM; Chavez, Craig A [Los Alamos, NM; Black, Marcie R [Lincoln, MA

2012-04-17

A method of manufacturing an article comprises providing a first sheet, wetting the first sheet with a liquid precursor to provide a first wet sheet, and irradiating the first wet sheet in a pattern corresponding to a first cross section of the article such that the liquid precursor is at least partially converted to a solid in the first cross section. A second sheet is disposed adjacent to the first sheet. The method further comprises wetting the second sheet with the liquid precursor to provide a second wet sheet, and irradiating the second wet sheet in a pattern corresponding to a second cross section of the article such that the liquid precursor is at least partially converted to a solid in the second cross section. In particular the liquid precursor may be converted to a metal, ceramic, semiconductor, semimetal, or a combination of these materials.

Variable selection based near infrared spectroscopy quantitative and qualitative analysis on wheat wet gluten

NASA Astrophysics Data System (ADS)

Lü, Chengxu; Jiang, Xunpeng; Zhou, Xingfan; Zhang, Yinqiao; Zhang, Naiqian; Wei, Chongfeng; Mao, Wenhua

2017-10-01

Wet gluten is a useful quality indicator for wheat, and short wave near infrared spectroscopy (NIRS) is a high performance technique with the advantage of economic rapid and nondestructive test. To study the feasibility of short wave NIRS analyzing wet gluten directly from wheat seed, 54 representative wheat seed samples were collected and scanned by spectrometer. 8 spectral pretreatment method and genetic algorithm (GA) variable selection method were used to optimize analysis. Both quantitative and qualitative model of wet gluten were built by partial least squares regression and discriminate analysis. For quantitative analysis, normalization is the optimized pretreatment method, 17 wet gluten sensitive variables are selected by GA, and GA model performs a better result than that of all variable model, with R2V=0.88, and RMSEV=1.47. For qualitative analysis, automatic weighted least squares baseline is the optimized pretreatment method, all variable models perform better results than those of GA models. The correct classification rates of 3 class of <24%, 24-30%, >30% wet gluten content are 95.45, 84.52, and 90.00%, respectively. The short wave NIRS technique shows potential for both quantitative and qualitative analysis of wet gluten for wheat seed.

The role of two isoenzymes of alpha-amylase of Araucaria araucana (Araucariaceae) on the digestion of starch granules during germination.

PubMed

Waghorn, Juana J; del Pozo, Talía; Acevedo, Elba A; Cardemil, Liliana A

2003-03-01

Starch is the principal reserve of Araucaria araucana seeds, and it is hydrolysed during germination mainly by alpha-amylase. There are several alpha-amylase isoenzymes whose patterns change in the embryo and in the megagametophyte from the one observed in quiescent seeds (T(0)) to a different one observed 90 h after imbibition (T(90)). The objective of this research was to study the roles of two purified alpha-amylase isoenzymes by in vitro digestion of starch granules extracted from the tissues at two times of imbibition: one is abundant in quiescent seeds and the other is abundant after 90 h of imbibition. The isoenzymes digested the starch granules of their own stage of germination better, since the isoenzyme T(0) digested starch granules mainly from quiescent seeds, while the isoenzyme T(90) digested starch mainly at 90 h of imbibition. The sizes of the starch granule and the tissue from which these granules originated make a difference to digestion by the isoenzymes. Embryonic isoenzyme T(0) digested large embryonic starch granules better than small and medium-sized granules, and better than those isolated from megagametophytes. Similarly isoenzyme T(90) digested small embryonic starch granules better than medium-sized and large granules, and better than those isolated from megagametophytes. However, a mixture of partially purified megagametophytic isoenzymes T(0) and T(90) digested the megagametophytic granules better than those isolated from embryos. Studies of in vitro sequential digestion of starch granules with these isoenzymes corroborated their specificity. The isoenzyme T(90) digested starch granules previously digested by the isoenzyme T(0). This suggests that in vivo these two isoenzymes may act sequentially in starch granule digestion.

Reducing the startup time of aerobic granular sludge reactors through seeding floccular sludge with crushed aerobic granules.

PubMed

Pijuan, Maite; Werner, Ursula; Yuan, Zhiguo

2011-10-15

One of the main challenging issues for the aerobic granular sludge technology is the long startup time when dealing with real wastewaters. This study presents a novel strategy to reduce the time required for granulation while ensuring a high level of nutrient removal. This new approach consists of seeding the reactor with a mixture of crushed aerobic granules and floccular sludge. The effectiveness of the strategy was demonstrated using abattoir wastewater, containing nitrogen and phosphorus at approximately 250 mgN/L and 30 mgP/L, respectively. Seven different mixtures of crushed granules and floccular sludge at granular sludge fractions (w/w in dry mass) of 0%, 5%, 10%, 15%, 25%, 30% and 50% were used to start eight granulation processes. The granulation time (defined as the time when the 10th percentile bacterial aggregate size is larger than 200 μm) displayed a strong dependency on the fraction of granular sludge. The shortest granulation time of 18 days was obtained with 50% crushed granules, in comparison with 133 days with 5% crushed granules. Full granulation was not achieved in the two trials without seeding with crushed granules. In contrast to the 100% floccular sludge cases, where a substantial loss of biomass occurred during granulation, the biomass concentration in all other trails did not decrease during granulation. This allowed that good nitrogen removal was maintained in all the reactors during the granulation process. However, enhanced biological phosphorus removal was achieved in only one of the eight trials. This was likely due to the temporary accumulation of nitrite, a strong inhibitor of polyphosphate accumulating organisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

Homologs of PROTEIN TARGETING TO STARCH Control Starch Granule Initiation in Arabidopsis Leaves[OPEN

PubMed Central

David, Laure C.; Abt, Melanie; Lu, Kuan-Jen

2017-01-01

The molecular mechanism that initiates the synthesis of starch granules is poorly understood. Here, we discovered two plastidial proteins involved in granule initiation in Arabidopsis thaliana leaves. Both contain coiled coils and a family-48 carbohydrate binding module (CBM48) and are homologs of the PROTEIN TARGETING TO STARCH (PTST) protein; thus, we named them PTST2 and PTST3. Chloroplasts in mesophyll cells typically contain five to seven granules, but remarkably, most chloroplasts in ptst2 mutants contained zero or one large granule. Chloroplasts in ptst3 had a slight reduction in granule number compared with the wild type, while those of the ptst2 ptst3 double mutant contained even fewer granules than ptst2. The ptst2 granules were larger but similar in morphology to wild-type granules, but those of the double mutant had an aberrant morphology. Immunoprecipitation showed that PTST2 interacts with STARCH SYNTHASE4 (SS4), which influences granule initiation and morphology. Overexpression of PTST2 resulted in chloroplasts containing many small granules, an effect that was dependent on the presence of SS4. Furthermore, isothermal titration calorimetry revealed that the CBM48 domain of PTST2, which is essential for its function, interacts with long maltooligosaccharides. We propose that PTST2 and PTST3 are critical during granule initiation, as they bind and deliver suitable maltooligosaccharide primers to SS4. PMID:28684429

Chromaffin granules in the rat adrenal medulla release their secretory content in a particulate fashion.

PubMed

Crivellato, Enrico; Belloni, Anna; Nico, Beatrice; Nussdorfer, Gastone G; Ribatti, Domenico

2004-03-01

Exocytosis is considered the main route of granule discharge in chromaffin cells. We recently provided ultrastructural evidence suggesting that piecemeal degranulation (PMD) occurs in mouse adrenal chromaffin cells. In the present study, we processed rat adrenal glands for transmission electron microscopy (TEM), and examined chromaffin cells for changes characteristic of PMD. Both adrenaline (A)- and noradrenaline (NA)-storing cells express ultrastructural features suggestive of a slow and particulate mode of granule discharge. In adrenaline-containing cells, some granules present enlarged dimensions accompanied by eroded or dissolved matrices. Likewise, a number of granules in NA-releasing cells show content reduction with variably expanded granule chambers. Dilated, empty granule containers are recognizable in the cytoplasm of both cell types. Characteristically, altered granules and empty containers are seen intermingled with normal, resting granules. In addition, chromaffin granules often show irregular profiles, with budding or tail-like projections of their limiting membranes. Thirty 150-nm-diameter membrane-bound vesicles with a moderately electron-dense or -lucent internal structure are observable in the cytoplasm of both cell types. These vesicles are seen among the granules and some of them are fused with the perigranule membranes in the process of attachment to or budding from the granules. These data add further support to the concept that PMD may be an alternative secretory pathway in adrenal chromaffin cells. Copyright 2004 Wiley-Liss, Inc.

Improved harvesting systems for wet sites

Treesearch

Bryce J. Stokes; Alvin Schilling

1997-01-01

Environmentally acceptable and economical forest operations are needed for sustainable management of forest resources. Improved methods for harvesting and transporting timber are especially needed for wet sites. As the demand for hardwood lumber continues to increase, improved and alternative methods are needed to ensure acceptance of timber harvesting for the wet site...

Injected mass deposition thresholds for lithium granule instigated triggering of edge localized modes on EAST

NASA Astrophysics Data System (ADS)

Lunsford, R.; Sun, Z.; Maingi, R.; Hu, J. S.; Mansfield, D.; Xu, W.; Zuo, G. Z.; Diallo, A.; Osborne, T.; Tritz, K.; Canik, J.; Huang, M.; Meng, X. C.; Gong, X. Z.; Wan, B. N.; Li, J. G.; the EAST Team

2018-03-01

The ability of an injected lithium granule to promptly trigger an edge localized mode (ELM) has been established in multiple experiments. By horizontally injecting granules ranging in diameter from 200 microns to 1 mm in diameter into the low field side of EAST H-mode discharges we have determined that granules with diameter  >600 microns are successful in triggering ELMs more than 95% of the time. It was also demonstrated that below 600 microns the triggering efficiency decreased roughly with granule size. Granules were radially injected from the outer midplane with velocities ~80 m s-1 into EAST upper single null discharges with an ITER like tungsten monoblock divertor. These granules were individually tracked throughout their injection cycle in order to determine their efficacy at triggering an ELM. For those granules of sufficient size, ELM triggering was a prompt response to granule injection. By simulating the granule injection with an experimentally benchmarked neutral gas shielding (NGS) model, the ablatant mass deposition required to promptly trigger an ELM is calculated and the fractional mass deposition is determined.

A universal laboratory method for determining physical parameters of radon migration in dry granulated porous media.

PubMed

Ye, Yong-Jun; Zhang, Yun-Feng; Dai, Xin-Tao; Ding, De-Xin

2017-10-01

The particle size and heaped methods of exhalation media have important effects on physical parameters, such as the free radon production rate, porosity, permeability, and radon diffusion coefficient. However, existing methods for determining those parameters are too complex, and time-consuming. In this study, a novel, systematic determining method was proposed based on nuclide decay, radon diffusion migration theory, and the mass conservation law, and an associated experimental device was designed and manufactured. The parameters of uranium ore heap and sandy soil of radon diffusion coefficient (D), free radon production rate (α), media permeability (k), and porosity (ε) were obtained. At the same time, the practicality of the novel determining method was improved over other methods, with the results showing that accuracy was within the acceptable range of experimental error. This novel method will be of significance for the study of radon migration and exhalation in granulated porous media. Copyright © 2017 Elsevier Ltd. All rights reserved.

Randomized, open-label, single-dose, crossover, relative bioavailability study in healthy adults, comparing the pharmacokinetics of rabeprazole granules administered using soft food or infant formula as dosing vehicle versus suspension.

PubMed

Thyssen, An; Solanki, Bhavna; Treem, William

2012-07-01

A sprinkle capsule formulation containing enteric-coated, delayed-release rabeprazole granules is being developed for the treatment of children with gastrointestinal reflux disease. The granules are designed to be mixed with vehicles that facilitate delivery to children, who may be unable to swallow solid formulations. The primary objective of this study-conducted on the sponsor's initiative-was to compare the bioavailability of rabeprazole granules when mixed with various dosing vehicles (small amount of soft food or infant formula) with that of a rabeprazole suspension with inactive vehicle granules (reference), to determine which dosing vehicle can be used to deliver rabeprazole in children. Tolerability was also assessed. This single-center, single-dose, randomized, open-label, 5-period crossover study was conducted in 35 healthy adult subjects. In a randomized sequence, fasting subjects received a single dose of 10-mg rabeprazole granules per treatment period, mixed with small amounts of 1 of 5 dosing vehicles (a strawberry-flavored suspension of rabeprazole granules with inactive vehicle granules reconstituted with water, yogurt [1 tablespoon], applesauce [1 tablespoon], or infant formula [5 mL], or a suspension of rabeprazole granules with inactive vehicle tablet reconstituted with water). Full plasma pharmacokinetic (PK) profiles of rabeprazole and its thioether metabolite were collected; concentrations were estimated via LC-MS/MS. PK properties were estimated using noncompartmental methods; 90% CIs around least squares mean test-to-reference ratios were calculated for C(max) and AUC values. All treatment-emergent adverse events (TEAEs) were recorded and assessed for severity (mild, moderate, or severe) and relationship to study drug. A total of 35 subjects were enrolled (mean age, 38 years; 54.3% female; 100% white; mean weight, 71.4 kg). Thirty-four subjects completed the study. Rabeprazole and rabeprazole thioether plasma PK properties were comparable between all of the dosing vehicles tested. Median T(max) was 2.5 to 3.0 hours, and mean elimination half-life was 1.27 to 1.43 hours. The 90%CIs for the least squares mean ratios for rabeprazole and rabeprazole thioether exposure were within the 80% to 125% bioequivalence limits for all relevant comparisons. All TEAEs were of mild or moderate intensity, with headache being the most commonly reported; 21 subjects (60%) experienced TEAEs during the study. No deaths or serious AEs were reported during the study; 1 subject experienced a TEAE (urinary tract infection) that led to the discontinuation of treatment. In these healthy adult subjects, the bioavailability of rabeprazole granules was comparable between all of the dosing vehicles tested, and rabeprazole was well tolerated. Soft food suitable for young children or infant formula may be appropriate for use as dosing vehicles for rabeprazole granules. Copyright © 2012 Elsevier HS Journals, Inc. All rights reserved.

Soft and Hard Textured Wheat Differ in Starch Properties as Indicated by Trimodal Distribution, Morphology, Thermal and Crystalline Properties

PubMed Central

Kumar, Rohit; Kumar, Aman; Sharma, Nand Kishor; Kaur, Navneet; Chunduri, Venkatesh; Chawla, Meenakshi; Sharma, Saloni; Singh, Kashmir; Garg, Monika

2016-01-01

Starch and proteins are major components in the wheat endosperm that affect its end product quality. Between the two textural classes of wheat i.e. hard and soft, starch granules are loosely bound with the lipids and proteins in soft wheat due to higher expression of interfering grain softness proteins. It might have impact on starch granules properties. In this work for the first time the physiochemical and structural properties of different sized starch granules (A-, B- and C-granules) were studied to understand the differences in starches with respect to soft and hard wheat. A-, B- and C-type granules were separated with >95% purity. Average number and proportion of A-, B-, and C-type granules was 18%, 56%, 26% and 76%, 19%, 5% respectively. All had symmetrical birefringence pattern with varied intensity. All displayed typical A-type crystallites. A-type granules also showed V-type crystallinity that is indicative of starch complexes with lipids and proteins. Granules differing in gelatinization temperature (ΔH) and transition temperature (ΔT), showed different enthalpy changes during heating. Substitution analysis indicated differences in relative substitution pattern of different starch granules. Birefringence, percentage crystallinity, transmittance, gelatinization enthalpy and substitution decreased in order of A>B>C being higher in hard wheat than soft wheat. Amylose content decreased in order of A>B>C being higher in soft wheat than hard wheat. Reconstitution experiment showed that starch properties could be manipulated by changing the composition of starch granules. Addition of A-granules to total starch significantly affected its thermal properties. Effect of A-granule addition was higher than B- and C-granules. Transmittance of the starch granules paste showed that starch granules of hard wheat formed clear paste. These results suggested that in addition to differences in protein concentration, hard and soft wheat lines have differences in starch composition also. PMID:26824830

Soft and Hard Textured Wheat Differ in Starch Properties as Indicated by Trimodal Distribution, Morphology, Thermal and Crystalline Properties.

PubMed

Kumar, Rohit; Kumar, Aman; Sharma, Nand Kishor; Kaur, Navneet; Chunduri, Venkatesh; Chawla, Meenakshi; Sharma, Saloni; Singh, Kashmir; Garg, Monika

2016-01-01

Starch and proteins are major components in the wheat endosperm that affect its end product quality. Between the two textural classes of wheat i.e. hard and soft, starch granules are loosely bound with the lipids and proteins in soft wheat due to higher expression of interfering grain softness proteins. It might have impact on starch granules properties. In this work for the first time the physiochemical and structural properties of different sized starch granules (A-, B- and C-granules) were studied to understand the differences in starches with respect to soft and hard wheat. A-, B- and C-type granules were separated with >95% purity. Average number and proportion of A-, B-, and C-type granules was 18%, 56%, 26% and 76%, 19%, 5% respectively. All had symmetrical birefringence pattern with varied intensity. All displayed typical A-type crystallites. A-type granules also showed V-type crystallinity that is indicative of starch complexes with lipids and proteins. Granules differing in gelatinization temperature (ΔH) and transition temperature (ΔT), showed different enthalpy changes during heating. Substitution analysis indicated differences in relative substitution pattern of different starch granules. Birefringence, percentage crystallinity, transmittance, gelatinization enthalpy and substitution decreased in order of A>B>C being higher in hard wheat than soft wheat. Amylose content decreased in order of A>B>C being higher in soft wheat than hard wheat. Reconstitution experiment showed that starch properties could be manipulated by changing the composition of starch granules. Addition of A-granules to total starch significantly affected its thermal properties. Effect of A-granule addition was higher than B- and C-granules. Transmittance of the starch granules paste showed that starch granules of hard wheat formed clear paste. These results suggested that in addition to differences in protein concentration, hard and soft wheat lines have differences in starch composition also.

[Value influence of different compatibilities of main active parts in yangyintongnao granule on pharmacokinetics parameters in rats with cerebral ischemia reperfusion injury by total amount statistic moment method].

PubMed

Guo, Ying; Yang, Jiehong; Znang, Hengyi; Fu, Xuchun; Zhnag, Yuyan; Wan, Haitong

2010-02-01

To study the influence of the different combinations of the main active parts in Yangyintongnao granule on the pharmacokinetics parameters of the two active components--ligustrazine and puerarin using the method of total amount statistic moment for pharmacokinetics. Combinations were formed according to the dosages of the four active parts (alkaloid, flavone, saponin, naphtha) by orthogonal experiment L9 (3(4)). Blood concentrations of ligustrazine and puerarin were determinated by HPLC at different time. Zero rank moment (AUC) and one rank moment (MRT, mean residence time) of ligustrazine and puerarin have been worked out to calculate the total amount statistic moment parameters was analyzed of Yangyintongnao granule by the method of the total amount statistic moment. The influence of different compatibilities on the pharmacokinetics parameters was analyzed by orthogonal test. Flavone has the strongest effect than saponin on the total AUC. Ligustrazine has the strongest effect on the total MRT. Saponin has little effect on the two parameters, but naphtha has more effect on both of them. It indicates that naphtha may promote metabolism of ligustrazine and puerarin in rat. Total amount statistic moment parameters can be used to guide for compatibilities of TCM.

Continuous twin screw granulation of controlled release formulations with various HPMC grades.

PubMed

Vanhoorne, V; Janssens, L; Vercruysse, J; De Beer, T; Remon, J P; Vervaet, C

2016-09-25

HPMC is a popular matrix former to formulate tablets with extended drug release. Tablets with HPMC are preferentially produced by direct compression. However, granulation is often required prior to tableting to overcome poor flowability of the formulation. While continuous twin screw granulation has been extensively evaluated for granulation of immediate release formulations, twin screw granulation of controlled release formulations including the dissolution behavior of the formulations received little attention. Therefore, the influence of the HPMC grade (viscosity and substitution degree) and the particle size of theophylline on critical quality attributes of granules (continuously produced via twin screw granulation) and tablets was investigated in the current study. Formulations with 20 or 40% HPMC, 20% theophylline and lactose were granulated with water at fixed process parameters via twin screw granulation. The torque was influenced by the viscosity and substitution degree of HPMC, but was not a limiting factor for the granulation process. An optimal L/S ratio was selected for each formulation based on the granule size distribution. The granule size distributions were influenced by the substitution degree and concentration of HPMC and the particle size of theophylline. Raman and UV spectroscopic analysis on 8 sieve fractions of granules indicated an inhomogeneous distribution of theophylline over the size fractions. However, this phenomenon was not correlated with the hydration rate or viscosity of HPMC. Controlled release of theophylline could be obtained over 24h with release profiles close to zero-order. The release of theophylline could be tailored via selection of the substitution degree and viscosity of HPMC. Copyright © 2016 Elsevier B.V. All rights reserved.

Stochastic Seeding Coupled with mRNA Self-Recruitment Generates Heterogeneous Drosophila Germ Granules.

PubMed

Niepielko, Matthew G; Eagle, Whitby V I; Gavis, Elizabeth R

2018-06-18

The formation of ribonucleoprotein assemblies called germ granules is a conserved feature of germline development. In Drosophila, germ granules form at the posterior of the oocyte in a specialized cytoplasm called the germ plasm, which specifies germline fate during embryogenesis. mRNAs, including nanos (nos) and polar granule component (pgc), that function in germline development are localized to the germ plasm through their incorporation into germ granules, which deliver them to the primordial germ cells. Germ granules are nucleated by Oskar (Osk) protein and contain varying combinations and quantities of their constituent mRNAs, which are organized as spatially distinct, multi-copy homotypic clusters. The process that gives rise to such heterogeneous yet organized granules remains unknown. Here, we show that individual nos and pgc transcripts can populate the same nascent granule, and these first transcripts then act as seeds, recruiting additional like transcripts to form homotypic clusters. Within a granule, homotypic clusters grow independently of each other but depend on the simultaneous acquisition of additional Osk. Although granules can contain multiple clusters of a particular mRNA, granule mRNA content is dominated by cluster size. These results suggest that the accumulation of mRNAs in the germ plasm is controlled by the mRNAs themselves through their ability to form homotypic clusters; thus, RNA self-association drives germ granule mRNA localization. We propose that a stochastic seeding and self-recruitment mechanism enables granules to simultaneously incorporate many different mRNAs while ensuring that each becomes enriched to a functional threshold. Copyright © 2018 Elsevier Ltd. All rights reserved.

Extended-release mesalamine granules for ulcerative colitis.

PubMed

Love, Bryan L; Miller, April D

2012-11-01

To evaluate the efficacy and safety of extended-release mesalamine granules in the maintenance of remission in ulcerative colitis (UC). Literature was obtained through searches of MEDLINE (1990-June 2012) using the terms mesalamine granules, ulcerative colitis, Apriso, and Salofalk. Bibliographies from retrieved articles were searched for additional citations. All English-language articles reporting on use of extended-release mesalamine granules in humans identified through the search were evaluated and included. The preferred initial treatment for induction and maintenance of remission in mild to moderate UC is agents from the 5-aminosalicylate class (balsalazide, mesalamine, olsalazine, sulfasalazine). Mesalamine granules are available as an encapsulated product in the US and as a nonencapsulated formulation in Europe. Data evaluating encapsulated mesalamine granules for induction of remission are lacking; however, the European mesalamine granule formulation has been evaluated for induction of remission. Patients receiving mesalamine granules for induction achieved clinical and endoscopic remission more frequently than those receiving placebo. Two pivotal, randomized, double-blind, placebo-controlled, multicenter studies have evaluated encapsulated mesalamine granules for maintenance in 562 adults in remission from UC. In both studies, the proportion of patients who remained relapse-free at 6 months was higher for those receiving encapsulated mesalamine granules than placebo. Mesalamine granules are well tolerated, with headache, nausea, and upper respiratory infections being the most frequently reported adverse effects. Current evidence supports the use of extended-release mesalamine granules for maintenance of remission in mild to moderate UC. Further studies are necessary to examine the ideal dose and regimen of encapsulated mesalamine granules for induction of remission in UC.

Preformulation considerations for controlled release dosage forms. Part II. Selected candidate support.

PubMed

Chrzanowski, Frank

2008-01-01

Practical examples of preformulation support of the form selected for formulation development are provided using several drug substances (DSs). The examples include determination of the solubilities vs. pH particularly for the range pH 1 to 8 because of its relationship to gastrointestinal (GI) conditions and dissolution method development. The advantages of equilibrium solubility and trial solubility methods are described. The equilibrium method is related to detecting polymorphism and the trial solubility method, to simplifying difficult solubility problems. An example of two polymorphs existing in mixtures of DS is presented in which one of the forms is very unstable. Accelerating stability studies are used in conjunction with HPLC and quantitative X-ray powder diffraction (QXRD) to demonstrate the differences in chemical and polymorphic stabilities. The results from two model excipient compatibility methods are compared to determine which has better predictive accuracy for room temperature stability. A DSC (calorimetric) method and an isothermal stress with quantitative analysis (ISQA) method that simulates wet granulation conditions were compared using a 2 year room temperature sample set as reference. An example of a pH stability profile for understanding stability and extrapolating stability to other environments is provided. The pH-stability of omeprazole and lansoprazole, which are extremely unstable in acidic and even mildly acidic conditions, are related to the formulation of delayed release dosage forms and the resolution of the problem associated with free carboxyl groups from the enteric coating polymers reacting with the DSs. Dissolution method requirements for CR dosage forms are discussed. The applicability of a modified disintegration time (DT) apparatus for supporting CR dosage form development of a pH sensitive DS at a specific pH such as duodenal pH 5.6 is related. This method is applicable for DSs such as peptides, proteins, enzymes and natural products where physical observation can be used in place of a difficult to perform analytical method, saving resources and providing rapid preformulation support.

The morphology of solar granulations and dark networks

NASA Astrophysics Data System (ADS)

Graves, J. Elon; Pierce, A. Keith

1986-08-01

Solar granules are classified into four groups based on shape and splitting by sharp rifts crossing them. Grains are classified as: single granules varying in size from 1/8 to 3 in., single granules embayed by a broad dark area or possessing a central darkening, single granules split by very narrow rifts which are significantly narrower than the intergranular lanes, and complexes of granules displaying a daisy pattern. The formation and growth of 'white-light dark networks' are also discussed

Statistical properties of solar granulation derived from the SOUP instrument on Spacelab 2

NASA Technical Reports Server (NTRS)

Title, A. M.; Tarbell, T. D.; Topka, K. P.; Ferguson, S. H.; Shine, R. A.

1989-01-01

Computer algorithms and statistical techniques were used to identify, measure, and quantify the properties of solar granulation derived from movies collected by the Solar Optical Universal Polarimeter on Spacelab 2. The results show that there is neither a typical solar granule nor a typical granule evolution. A granule's evolution is dependent on local magnetic flux density, its position with respect to the active region plage, its position in the mesogranulation pattern, and the evolution of granules in its immediate neighborhood.

Effect of suspension property on granule morphology and compaction behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hae-Weon Lee, Guesup Song, In-Sik Suk

1995-12-31

Granule morphology is an important factor during dry pressing, since it has great influences on die flowability, compaction ratio, and resulting green microstructure. Granule morphology and packing structure of ultrafine Si{sub 3}N{sub 4} particles in the granule were optimized during spray drying by adjusting the suspension structure. The particle packing structure of spray-dried granule was investigated with suspension structure. The effects of granule morphology and its particle packing structure on compaction and resultant sintering behavior were evaluated.

The use of Rheology Combined with Differential Scanning Calorimetry to Elucidate the Granulation Mechanism of an Immiscible Formulation During Continuous Twin-Screw Melt Granulation.

PubMed

Monteyne, Tinne; Heeze, Liza; Mortier, Severine Therese F C; Oldörp, Klaus; Cardinaels, Ruth; Nopens, Ingmar; Vervaet, Chris; Remon, Jean-Paul; De Beer, Thomas

2016-10-01

Twin screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to continuous granulation of moisture sensitive drugs. However, knowledge of the material behavior during TS HMG is crucial to optimize the formulation, process and resulting granule properties. The aim of this study was to evaluate the agglomeration mechanism during TS HMG using a rheometer in combination with differential scanning calorimetry (DSC). An immiscible drug-binder formulation (caffeine-Soluplus(®)) was granulated via TS HMG in combination with thermal and rheological analysis (conventional and Rheoscope), granule characterization and Near Infrared chemical imaging (NIR-CI). A thin binder layer with restricted mobility was formed on the surface of the drug particles during granulation and is covered by a second layer with improved mobility when the Soluplus(®) concentration exceeded 15% (w/w). The formation of this second layer was facilitated at elevated granulation temperatures and resulted in smaller and more spherical granules. The combination of thermal and rheological analysis and NIR-CI images was advantageous to develop in-depth understanding of the agglomeration mechanism during continuous TS HMG and provided insight in the granule properties as function of process temperature and binder concentration.

Experimental Studies on Behaviour of Reinforced Geopolymer Concrete Beams Subjected to Monotonic Static Loading

NASA Astrophysics Data System (ADS)

Madheswaran, C. K.; Ambily, P. S.; Dattatreya, J. K.; Ramesh, G.

2015-06-01

This work describes the experimental investigation on behaviour of reinforced GPC beams subjected to monotonic static loading. The overall dimensions of the GPC beams are 250 mm × 300 mm × 2200 mm. The effective span of beam is 1600 mm. The beams have been designed to be critical in shear as per IS:456 provisions. The specimens were produced from a mix incorporating fly ash and ground granulated blast furnace slag, which was designed for a compressive strength of 40 MPa at 28 days. The reinforced concrete specimens are subjected to curing at ambient temperature under wet burlap. The parameters being investigated include shear span to depth ratio (a/d = 1.5 and 2.0). Experiments are conducted on 12 GPC beams and four OPCC control beams. All the beams are tested using 2000 kN servo-controlled hydraulic actuator. This paper presents the results of experimental studies.

Studies on the compressibility of wax matrix granules of acetaminophen and their admixtures with various tableting bases.

PubMed

Uhumwangho, M U; Okor, R S

2006-04-01

Matrix granules of acetaminophen have been formed by a melt granulation process whereby the acetaminophen powder was triturated with the melted wax--goat wax, glyceryl monostearate or carnuba wax. The compressibility of the matrix granules and their admixture, with diluent granules (lactose, alpha-cellulose or microcrystalline cellulose) was investigated. The granules were compressed to tablets at a constant load (30 arbitrary units on the load scale) of a manesty single punch machine. Resulting tablets were evaluated for tensile strength (T) and disintegration times (DT). Granule flow was determined by measuring their angle of repose when allowed to fall freely on a level surface. Matrix granules prepared by melt granulation with goat wax or glyceryl monostearate were too sticky and therefore did not flow at all. They were also poorly compressible (T values = 0.20MN/m2). Inclusion of the diluent remarkably improved granule flow property and compressibility. The T values of the tablets (measure of compressibility) increased from about 0.24 to 0.65 MN/m2 during increase in diluent (lactose) content from 20 to 80 %w/w. Microcrystalline cellulose and alpha-cellulose were more effective than lactose in promoting compressibility of the granules. By contrast the matrix granules formed with carnuba wax were free flowing (angle of repose, 18.60). Addition of the diluent further improved flowability slightly. The matrix granules (without a diluent) were readily compressible (T value, 1.79MN/m2). Addition of the diluent (80%w/w) reduced T values (MN/m2) slightly to 1.32 (lactose), 1.48 (alpha-cellulose) and 1.74 (microcrystalline cellulose). Tablets of the matrix granules only, disintegrated rapidly within 3 minutes. DT was further reduced to <30 s by addition of any of the diluents. The indication is that the inclusion of the diluents studied can be used to improve the compressibility of the otherwise poorly compressible matrix granules. Based on the flowability, compressibility, and disintegration data, carnuba wax proved most promising in the melt granulation of the test drug for sustained release applications.

Fast formation of aerobic granules by combining strong hydraulic selection pressure with overstressed organic loading rate.

PubMed

Liu, Yong-Qiang; Tay, Joo-Hwa

2015-09-01

The combined strong hydraulic selection pressure (HSP) with overstressed organic loading rate (OLR) as a fast granulation strategy was used to enhance aerobic granulation. To investigate the wide applicability of this strategy to different scenarios and its relevant mechanism, different settling times, different inoculums, different exchange ratios, different reactor configurations, and different shear force were used in this study. It was found that clear granules were formed within 24 h and steady state reached within three days when the fast granulation strategy was used in a lab-scale reactor seeded with well settled activated sludge (Reactor 2). However, granules appeared after 2-week operation and reached steady state after one month at the traditional step-wise decreased settling time from 20 to 2 min with OLR of 6 g COD/L·d (Reactor 1). With the fast granulation strategy, granules appeared within 24 h even with bulking sludge as seed to start up Reactor 3, but 6-day lag phase was observed compared with Reactor 2. Both Reactor 2 and Reactor 3 experienced sigmoidal growth curve in terms of biomass accumulation and granule size increase after granulation. In addition, the reproducible results in pilot-scale reactors (Reactor 5 and Reactor 6) with diameter of 20 cm and height/diameter ratio (H/D) of 4 further proved that reactor configuration and fluid flow pattern had no effect on the aerobic granulation when the fast granulation strategy was employed, but biomass accumulation experienced a short lag phase too in Reactor 5 and Reactor 6. Although overstressed OLR was favorable for fast granulation, it also led to the fluffy granules after around two-week operation. However, the stable 6-month operation of Reactor 3 demonstrated that the rapidly formed granules were able to maintain long-term stability by reducing OLR from 12 g COD/L·d to 6 g COD/L·d. A mechanism of fast granulation with the strategy of combined strong HSP and OLR was proposed to explain results and guide the operation with this fast strategy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling of lithium granule injection in NSTX using M3D-C1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fil, A.; Kolemen, E.; Ferraro, N.

In this paper, we present simulations of pedestal control by lithium granule injection (LGI) in NSTX. A model for small granule ablation has been implemented in the M3D-C1 code (Jardin et al 2012 Comput. Sci. Discovery 5 014002), allowing the simulation of realistic lithium granule injections. 2D and 3D simulations of Li injections in NSTX H-mode plasmas are performed and the effect of granule size, injection angle and velocity on the pedestal gradient increase is studied. The amplitude of the local pressure perturbation caused by the granules is found to be highly dependent on the solid granule size. Adjusting themore » granule injection velocity allows one to inject more particles at the pedestal top. 3D simulations show the destabilization of high order MHD modes whose amplitude is directly linked to the localized pressure perturbation, which is found to depend on the toroidal localization of the granule density source.« less

Autophagy meets fused in sarcoma-positive stress granules.

PubMed

Matus, Soledad; Bosco, Daryl A; Hetz, Claudio

2014-12-01

Mutations in fused in sarcoma and/or translocated in liposarcoma (FUS, TLS or FUS) are linked to familial cases of amyotrophic lateral sclerosis (ALS). Mutant FUS selectively accumulates into discrete cytosolic structures known as stress granules under various stress conditions. In addition, mutant FUS expression can alter the dynamics and morphology of stress granules. Although the link between mutant FUS and stress granules is well established, the mechanisms modulating stress granule formation and disassembly in the context of ALS are poorly understood. In this issue of Neurobiology of Aging, Ryu et al. uncover the impact of autophagy on the potential toxicity of mutant FUS-positive stress granules. The authors provide evidence indicating that enhanced autophagy activity reduces the number of stress granules, which in the case of cells containing mutant FUS-positive stress granules, is neuroprotective. Overall, this study identifies an intersection between the proteostasis network and alterations in RNA metabolism in ALS through the dynamic assembly and disassembly of stress granules. Copyright © 2014 Elsevier Inc. All rights reserved.

Internal structure of normal maize starch granules revealed by chemical surface gelatinization.

PubMed

Pan, D D; Jane, J I

2000-01-01

Normal maize starch was fractionated into two sizes: large granules with diameters more than 5 microns and small granules with diameters less than 5 microns. The large granules were surface gelatinized by treating them with an aqueous LiCl solution (13 M) at 22-23 degrees C. Surface-gelatinized remaining granules were obtained by mechanical blending, and gelatinized surface starch was obtained by grinding with a mortar and a pestle. Starches of different granular sizes and radial locations, obtained after different degrees of surface gelatinization, were subjected to scanning electron microscopy, iodine potentiometric titration, gel-permeation chromatography, and amylopectin branch chain length analysis. Results showed that the remaining granules had a rough surface with a lamella structure. Amylose was more concentrated at the periphery than at the core of the granule. Amylopectin had longer long B-chains at the core than at the periphery of the granule. Greater proportions of the long B-chains were present at the core than at the periphery of the granule.

New Class of Cargo Protein in Tetrahymena thermophila Dense Core Secretory Granules

PubMed Central

Haddad, Alex; Bowman, Grant R.; Turkewitz, Aaron P.

2002-01-01

Regulated exocytosis of dense core secretory granules releases biologically active proteins in a stimulus-dependent fashion. The packaging of the cargo within newly forming granules involves a transition: soluble polypeptides condense to form water-insoluble aggregates that constitute the granule cores. Following exocytosis, the cores generally disassemble to diffuse in the cell environment. The ciliates Tetrahymena thermophila and Paramecium tetraurelia have been advanced as genetically manipulatable systems for studying exocytosis via dense core granules. However, all of the known granule proteins in these organisms condense to form the architectural units of lattices that are insoluble both before and after exocytosis. Using an approach designed to detect new granule proteins, we have now identified Igr1p (induced during granule regeneration). By structural criteria, it is unrelated to the previously characterized lattice-forming proteins. It is distinct in that it is capable of dissociating from the insoluble lattice following secretion and therefore represents the first diffusible protein identified in ciliate granules. PMID:12456006

Modeling of lithium granule injection in NSTX using M3D-C1

DOE PAGES

Fil, A.; Kolemen, E.; Ferraro, N.; ...

2017-04-06

In this paper, we present simulations of pedestal control by lithium granule injection (LGI) in NSTX. A model for small granule ablation has been implemented in the M3D-C1 code (Jardin et al 2012 Comput. Sci. Discovery 5 014002), allowing the simulation of realistic lithium granule injections. 2D and 3D simulations of Li injections in NSTX H-mode plasmas are performed and the effect of granule size, injection angle and velocity on the pedestal gradient increase is studied. The amplitude of the local pressure perturbation caused by the granules is found to be highly dependent on the solid granule size. Adjusting themore » granule injection velocity allows one to inject more particles at the pedestal top. 3D simulations show the destabilization of high order MHD modes whose amplitude is directly linked to the localized pressure perturbation, which is found to depend on the toroidal localization of the granule density source.« less

Biomineralisation by earthworms - an investigation into the stability and distribution of amorphous calcium carbonate.

PubMed

Hodson, Mark E; Benning, Liane G; Demarchi, Bea; Penkman, Kirsty E H; Rodriguez-Blanco, Juan D; Schofield, Paul F; Versteegh, Emma A A

Many biominerals form from amorphous calcium carbonate (ACC), but this phase is highly unstable when synthesised in its pure form inorganically. Several species of earthworm secrete calcium carbonate granules which contain highly stable ACC. We analysed the milky fluid from which granules form and solid granules for amino acid (by liquid chromatography) and functional group (by Fourier transform infrared (FTIR) spectroscopy) compositions. Granule elemental composition was determined using inductively coupled plasma-optical emission spectroscopy (ICP-OES) and electron microprobe analysis (EMPA). Mass of ACC present in solid granules was quantified using FTIR and compared to granule elemental and amino acid compositions. Bulk analysis of granules was of powdered bulk material. Spatially resolved analysis was of thin sections of granules using synchrotron-based μ-FTIR and EMPA electron microprobe analysis. The milky fluid from which granules form is amino acid-rich (≤ 136 ± 3 nmol mg -1 (n = 3; ± std dev) per individual amino acid); the CaCO 3 phase present is ACC. Even four years after production, granules contain ACC. No correlation exists between mass of ACC present and granule elemental composition. Granule amino acid concentrations correlate well with ACC content (r ≥ 0.7, p ≤ 0.05) consistent with a role for amino acids (or the proteins they make up) in ACC stabilisation. Intra-granule variation in ACC (RSD = 16%) and amino acid concentration (RSD = 22-35%) was high for granules produced by the same earthworm. Maps of ACC distribution produced using synchrotron-based μ-FTIR mapping of granule thin sections and the relative intensity of the ν 2 : ν 4 peak ratio, cluster analysis and component regression using ACC and calcite standards showed similar spatial distributions of likely ACC-rich and calcite-rich areas. We could not identify organic peaks in the μ-FTIR spectra and thus could not determine whether ACC-rich domains also had relatively high amino acid concentrations. No correlation exists between ACC distribution and elemental concentrations determined by EMPA. ACC present in earthworm CaCO 3 granules is highly stable. Our results suggest a role for amino acids (or proteins) in this stability. We see no evidence for stabilisation of ACC by incorporation of inorganic components. Graphical abstractSynchrotron-based μ-FTIR mapping was used to determine the spatial distribution of amorphous calcium carbonate in earthworm-produced CaCO 3 granules.

Nanotextured Surfaces and Related Methods, Systems, and Uses

NASA Technical Reports Server (NTRS)

Greer, Harold F. (Inventor); Greer, Julia R. (Inventor)

2014-01-01

A method of controlling wetting characteristics is described. Such method includes forming and configuring nanostructures on a surface where controlling of the wetting characteristics is desired. Surfaces and methods of fabricating such surfaces are also described.

[Experiment research of Jiajian Yunvjian granules on hyperthyroidism graves].

PubMed

Guo, Juan; Chen, Changxun; Li, Xin

2009-09-01

To investigate the effects and the related mechanisms of Jiajian Yunujian (JJYNJ) granules, which were made from traditional Chinese medicinal prescription, on hyperthyroidism graves. Except that in the normal group, all mice were injected 350 mcirog x kg x d(-1) L-Thyroxin sodium to establish the hyperthyroidism graves model. The model mice were divided randomly into model control group, 3 different groups of JJYNJ granules at oral dosage of 2.17, 4.33, 8.66 g x kg(-1), every day and thiamazole group at oral dosage of 10 mg x kg(-1) every day, respectively. The body weight, heart/body weight index, heart rate (HR), spontaneous activity and oxygen consumption of all the mice were measured. The serum T3, T4 levels were evaluated with the method of RIA. Meanwhile, the effect of JJYNJ granules and thiamazole on iodine uptake by thyroid was determined by radio-assay. JJYNJ granules could improve the symptoms caused by thyroxin, increase body weight (P < 0.05), reduce heart/body weight index, spontaneous activity and oxygen consumption (P < 0.05). The HR of model group was (794.5 +/- 47.8) beats x min(-1), significantly faster than that of normal group (682.5 +/- 116.4) beats x min(-1). Those of low, middle and high JJYNJ granule group were (736.9 +/- 66.6), (742.1 +/- 62.3), (715.8 +/- 102.8) beats x min(-1) respectively, obviously slower than that of model group (P < 0.05). The serum T3, T4 levels of model group were (3.85 +/- 0.960), (234.46 +/- 58.11) microg x L(-1), significantly higher than those of normal group (0.99 +/- 0.30), (65.94 +/- 13.94) microg x L(-1), P < 0.01). Those of middle, high of JJYNJ granule group were (2.57 +/- 0.81), (164.27 +/- 72.63) microg x L(-1) and (2.70 +/- 0.55), (157.26 +/- 35.03) microg x L(-1). Those of thiamazole group were (2.88 +/- 0.59), (172.65 +/- 39.73) miicrog x L(-1). These values were significantly lower than those of model group. Thiamazole could significantly inhibit the iodine uptake in thyroid (P < 0.01), but JJYNJ granules did not block that obviously. JJYNJ granules could significantly improve the symptoms of experimental hyperthyroidism graves. Its mechanisms may be different from that of thiamazole, which is related to inhibiting the synthesis of thyroxin in thyroid.

Effectiveness of Diflubenzuron in the control of houseflies.

PubMed

Tilak, Rina; Verma, A K; Wankhade, Urmila B

2010-06-01

Houseflies are one of the major pest problems worldwide. The current housefly control strategy in the country hinges on the use of Dichlorvos as a housefly larvicide and pyrethrum spray in kitchens/dining areas. The present study was undertaken to evaluate the newer housefly control options in the wake of concerns about human toxicity of Dichlorvos and its continued use in public health. Efficacy of Diflubenzuron WP and granule formulations (chitin synthesis inhibitor) vis-à-vis Dichlorvos EC in the control of housefly was assessed in laboratory by adult emergence inhibition after treatment and in field conditions by estimation of density post-application up to three weeks using standard methods. Dichlorvos EC and Diflubenzuron formulations (WP and granule) brought about 100% inhibition of adult emergence under laboratory conditions. However, in the field evaluation, effective suppression of housefly population was brought about by Dichlorvos and Diflubenzuron granule formulation (though delayed). Dichlorvos EC and Diflubenzuron granule formulation are effective housefly larvicides. It is recommended that Diflubenzuron WP formulation be evaluated at a higher frequency to enhance its effectiveness and its use may be considered in conjunction with an initial suppression of housefly adults with an adulticide, e.g. Cyphenothrin, etc.

Tumors of the endocrine/neuroendocrine system: an overview.

PubMed

Erlandson, R A; Nesland, J M

1994-01-01

For the sake of discussion, the markedly diversified tumors of the endocrine/neuroendocrine system are classified as those originating in classic epithelial endocrine organs (eg, adrenal cortical adenomas), from the diffuse endocrine cells (eg, jejunal carcinoid tumors), or from clusters of these cells (eg, islet cell tumors); and those arising from neurosecretory neurons (eg, neuroblastoma) or paraganglia (eg, carotid body tumor). Although traditional transmission electron microscopy is useful for identifying neurosecretory or endosecretory granules as such, with few exceptions (eg, insulin-containing granules with a complex paracrystalline core) it is not possible to ascribe a granule type (size, shape, or ultrastructure) to a distinct nosologic entity or secretory product because of their overlapping fine structures in different cell types. Immunoelectron microscopy methods utilizing colloidal gold-labeled secondary antibodies can be used to localize virtually any antigen (peptide or neuroamine) to a specific neurosecretory or endosecretory granule or other cell structure. General endocrine/neuroendocrine cell markers such as neuron-specific enolase, the chromogranins, and synaptophysin are useful in identifying neuroendocrine differentiation in a neoplasm using routine immunohistochemical procedures. The current relevance of the APUD concept of Pearse as well as the biologic importance of endocrine/neuroendocrine secretory products such as bombesin and insulinlike growth factors also are discussed.

Latent variable modeling to analyze the effects of process parameters on the dissolution of paracetamol tablet

PubMed Central

Sun, Fei; Xu, Bing; Zhang, Yi; Dai, Shengyun; Shi, Xinyuan; Qiao, Yanjiang

2017-01-01

ABSTRACT The dissolution is one of the critical quality attributes (CQAs) of oral solid dosage forms because it relates to the absorption of drug. In this paper, the influence of raw materials, granules and process parameters on the dissolution of paracetamol tablet was analyzed using latent variable modeling methods. The variability in raw materials and granules was understood based on the principle component analysis (PCA), respectively. A multi-block partial least squares (MBPLS) model was used to determine the critical factors affecting the dissolution. The results showed that the binder amount, the post granulation time, the API content in granule, the fill depth and the punch tip separation distance were the critical factors with variable importance in the projection (VIP) values larger than 1. The importance of each unit of the whole process was also ranked using the block importance in the projection (BIP) index. It was concluded that latent variable models (LVMs) were very useful tools to extract information from the available data and improve the understanding on dissolution behavior of paracetamol tablet. The obtained LVMs were also helpful to propose the process design space and to design control strategies in the further research. PMID:27689242

Imaging exocytosis of single glucagon-like peptide-1 containing granules in a murine enteroendocrine cell line with total internal reflection fluorescent microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohara-Imaizumi, Mica; Aoyagi, Kyota; Akimoto, Yoshihiro

To analyze the exocytosis of glucagon-like peptide-1 (GLP-1) granules, we imaged the motion of GLP-1 granules labeled with enhanced yellow fluorescent protein (Venus) fused to human growth hormone (hGH-Venus) in an enteroendocrine cell line, STC-1 cells, by total internal reflection fluorescent (TIRF) microscopy. We found glucose stimulation caused biphasic GLP-1 granule exocytosis: during the first phase, fusion events occurred from two types of granules (previously docked granules and newcomers), and thereafter continuous fusion was observed mostly from newcomers during the second phase. Closely similar to the insulin granule fusion from pancreatic {beta} cells, the regulated biphasic exocytosis from two typesmore » of granules may be a common mechanism in glucose-evoked hormone release from endocrine cells.« less

High organic loading influences the physical characteristics of aerobic sludge granules.

PubMed

Moy, B Y-P; Tay, J-H; Toh, S-K; Liu, Y; Tay, S T-L

2002-01-01

The effect of high organic loading rate (OLR) on the physical characteristics of aerobic granules was studied. Two column-type sequential aerobic sludge blanket reactors were fed with either glucose or acetate as the main carbon source, and the OLR was gradually raised from 6 to 9, 12 and 15 kg chemical oxygen demand (COD) m(-3) d(-1). Glucose-fed granules could sustain the maximum OLR tested. At a low OLR, these granules exhibited a loose fluffy morphology dominated by filamentous bacteria. At higher OLRs, these granules became irregularly shaped, with folds, crevices and depressions. In contrast, acetate-fed granules had a compact spherical morphology at OLRs of 6 and 9 kg COD m(-3) d(-1), with better settling and strength characteristics than glucose-fed granules at similar OLRs. However, acetate-fed granules could not sustain high OLRs and disintegrated when the OLR reached 9 kg COD m(-3) d(-1). The compact regular microstructure of the acetate-fed granules appeared to limit mass transfer of nutrients at an OLR of 9 kg COD m(-3) d(-1). The looser filamentous microstructure of the glucose-fed granules and the subsequent irregular morphology delayed the onset of diffusion limitation and allowed significantly higher OLRs to be attained. SIGNIFICNACE AND IMPACT OF THE STUDY: High organic loading rates are possible with aerobic granules. This research would be helpful in the development of aerobic granule-based systems for high-strength wastewaters.

Granulation of snow: From tumbler experiments to discrete element simulations

NASA Astrophysics Data System (ADS)

Steinkogler, Walter; Gaume, Johan; Löwe, Henning; Sovilla, Betty; Lehning, Michael

2015-06-01

It is well known that snow avalanches exhibit granulation phenomena, i.e., the formation of large and apparently stable snow granules during the flow. The size distribution of the granules has an influence on flow behavior which, in turn, affects runout distances and avalanche velocities. The underlying mechanisms of granule formation are notoriously difficult to investigate within large-scale field experiments, due to limitations in the scope for measuring temperatures, velocities, and size distributions. To address this issue we present experiments with a concrete tumbler, which provide an appropriate means to investigate granule formation of snow. In a set of experiments at constant rotation velocity with varying temperatures and water content, we demonstrate that temperature has a major impact on the formation of granules. The experiments showed that granules only formed when the snow temperature exceeded -1∘C. No evolution in the granule size was observed at colder temperatures. Depending on the conditions, different granulation regimes are obtained, which are qualitatively classified according to their persistence and size distribution. The potential of granulation of snow in a tumbler is further demonstrated by showing that generic features of the experiments can be reproduced by cohesive discrete element simulations. The proposed discrete element model mimics the competition between cohesive forces, which promote aggregation, and impact forces, which induce fragmentation, and supports the interpretation of the granule regime classification obtained from the tumbler experiments. Generalizations, implications for flow dynamics, and experimental and model limitations as well as suggestions for future work are discussed.

Statistical properties of solar granulation from the SOUP instrument on Spacelab 2

NASA Astrophysics Data System (ADS)

Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

1988-11-01

The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution.

Statistical properties of solar granulation from the SOUP instrument on Spacelab 2

NASA Technical Reports Server (NTRS)

Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

1988-01-01

The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution.

Investigation on the pitting of potato starch granules during high frequency ultrasound treatment.

PubMed

Bai, Wenzhe; Hébraud, Pascal; Ashokkumar, Muthupandian; Hemar, Yacine

2017-03-01

In this paper, the pitting of potato starch granules in aqueous suspensions (1%) by high-frequency high-power ultrasound (850kHz at a power of 0.2W, 2W or 3.7W; and also 500kHz and 1MHz at a power of 2W) is reported. The number of pits per starch granules was found to be independent of the amylose content of starches, and the surface properties of starch granules as modified through SDS and ethanol washing. At 850kHz, the maximum number of pits per starch granule, for both normal and waxy starches, did not exceed 11. However, a close inspection of fractionated starch granules based on their sizes showed that there is an optimum granule size for which a maximum pit number is obtained. For example, starch granules with diameter size range of ∼15 to ∼30μm had a maximum pit number (between 10 and 20 pits per granule) when sonicated (2W, 850kHz and 30min); while sonication of small (<10μm) and very large (>45μm) granules resulted in a smaller number of pits per granule (∼5). Further, the maximum number of pits per granules is also found to be proportional to the ultrasound frequency, with values of approximately 7, 10 and 11 at 0.50, 0.85, and 1MHz, respectively. FTIR measurements did not show any breakup of starch molecules. Copyright © 2016 Elsevier B.V. All rights reserved.

Collection of Wet-Origin Footwear Impressions on Various Surfaces Using an Electrostatic Dust Print Lifter.

PubMed

Hong, Sungwook; Park, Miseon

2018-01-19

Electrostatic dust print lift method is known to be able to recover only dry-origin footwear impression. However, the wet-origin footwear impression could also be recovered using this method. As the amount of dust accumulated before deposition of the wet-origin footwear impression increased, the intensity of the footwear impression lifted with this method became stronger. If the footwear impression is not affected by moisture after it is made, the 28-h old wet-origin footwear impression could be recovered using this method. The intensity of the lifted footwear impression did not decrease significantly even when the number of sequential steps increased as long as the shoe sole is wet. However, when the moisture on the shoe sole depleted, the intensity of the footwear impression decreased sharply. This method has the advantage of being able to enhance the footwear impression without being affected by the footwear impressions deposited in the past. © 2018 American Academy of Forensic Sciences.

Constraining Convection Properties with VLTI

NASA Astrophysics Data System (ADS)

Paladini, Claudia

2018-04-01

We recently imaged the stellar surface of the asymptotic giant branch (AGB) star pi1 Gruis using the PIONIER instrument mounted on the Very Large Telescope Interferometer. The three images are very little contaminated by molecular and dust opacity, and show a stellar surface characterized by large convective granulation. In this contribution I will describe the method used to derive the size of the granulation pattern, the challenges of image reconstruction, and our results. I will conclude describing shortly what the next generation of interferometric instruments will bring to our study.

Starch synthase 4 is essential for coordination of starch granule formation with chloroplast division during Arabidopsis leaf expansion

PubMed Central

Crumpton-Taylor, Matilda; Pike, Marilyn; Lu, Kuan-Jen; Hylton, Christopher M; Feil, Regina; Eicke, Simona; Lunn, John E; Zeeman, Samuel C; Smith, Alison M

2013-01-01

Arabidopsis thaliana mutants lacking the SS4 isoform of starch synthase have strongly reduced numbers of starch granules per chloroplast, suggesting that SS4 is necessary for the normal generation of starch granules. To establish whether it plays a direct role in this process, we investigated the circumstances in which granules are formed in ss4 mutants. Starch granule numbers and distribution and the accumulation of starch synthase substrates and products were investigated during ss4 leaf development, and in ss4 mutants carrying mutations or transgenes that affect starch turnover or chloroplast volume. We found that immature ss4 leaves have no starch granules, but accumulate high concentrations of the starch synthase substrate ADPglucose. Granule numbers are partially restored by elevating the capacity for glucan synthesis (via expression of bacterial glycogen synthase) or by increasing the volumes of individual chloroplasts (via introduction of arc mutations). However, these granules are abnormal in distribution, size and shape. SS4 is an essential component of a mechanism that coordinates granule formation with chloroplast division during leaf expansion and determines the abundance and the flattened, discoid shape of leaf starch granules. PMID:23952675

Granule size control and targeting in pulsed spray fluid bed granulation.

PubMed

Ehlers, Henrik; Liu, Anchang; Räikkönen, Heikki; Hatara, Juha; Antikainen, Osmo; Airaksinen, Sari; Heinämäki, Jyrki; Lou, Honxiang; Yliruusi, Jouko

2009-07-30

The primary aim of the study was to investigate the effects of pulsed liquid feed on granule size. The secondary aim was to increase knowledge of this technique in granule size targeting. Pulsed liquid feed refers to the pump changing between on- and off-positions in sequences, called duty cycles. One duty cycle consists of one on- and off-period. The study was performed with a laboratory-scale top-spray fluid bed granulator with duty cycle length and atomization pressure as studied variables. The liquid feed rate, amount and inlet air temperature were constant. The granules were small, indicating that the powder has only undergone ordered mixing, nucleation and early growth. The effect of atomizing pressure on granule size depends on inlet air relative humidity, with premature binder evaporation as a reason. The duty cycle length was of critical importance to the end product attributes, by defining the extent of intermittent drying and rewetting. By varying only the duty cycle length, it was possible to control granule nucleation and growth, with a wider granule size target range in increased relative humidity. The present study confirms that pulsed liquid feed in fluid bed granulation is a useful tool in end product particle size targeting.

Stimulation of microtubule-based transport by nucleation of microtubules on pigment granules

PubMed Central

Semenova, Irina; Gupta, Dipika; Usui, Takeo; Hayakawa, Ichiro; Cowan, Ann; Rodionov, Vladimir

2017-01-01

Microtubule (MT)-based transport can be regulated through changes in organization of MT transport tracks, but the mechanisms that regulate these changes are poorly understood. In Xenopus melanophores, aggregation of pigment granules in the cell center involves their capture by the tips of MTs growing toward the cell periphery, and granule aggregation signals facilitate capture by increasing the number of growing MT tips. This increase could be explained by stimulation of MT nucleation either on the centrosome or on the aggregate of pigment granules that gradually forms in the cell center. We blocked movement of pigment granules to the cell center and compared the MT-nucleation activity of the centrosome in the same cells in two signaling states. We found that granule aggregation signals did not stimulate MT nucleation on the centrosome but did increase MT nucleation activity of pigment granules. Elevation of MT-nucleation activity correlated with the recruitment to pigment granules of a major component of MT-nucleation templates, γ-tubulin, and was suppressed by γ-tubulin inhibitors. We conclude that generation of new MT transport tracks by concentration of the leading pigment granules provides a positive feedback loop that enhances delivery of trailing granules to the cell center. PMID:28381426

Localization and characterization of carbohydrates in adrenal medullary cells

PubMed Central

1975-01-01

The localization and characterization of carbohydrates in adrenal medullary cells were studied by histochemical and cytochemical methods. Adrenaline (A)-and noradrenaline (N)-storing granules were argentaphobic when ultrathin sections of Araldite-embedded medullae were stained according to the periodic acid-thiocarbohydrazide-silver proteinate technique of Thiery. A small amount of glycogen in the form of single beta-particles as well as lysosomes were, however, visualized by this technique. The entire core of the A granules was markedly positive after ultrathin sections of glutaraldehyde-fixed, glycol methacrylate (GMA)-embedded medullae were stained with phosphotungstic acid (PTA) at low pH (0.3). The N granules, in contrast, were mostly unreactive. In the A cells, PTA stained a large part of the Golgi complex, whereas in the N cells the Golgi complex was mostly unstained. In both cell types, the cell coat, lysosomes, and multivesticular bodies reacted to PTA. The periodic acid-Schiff (PAS) technique showed A but not N granules in semithin sections of GMA- or Araldite-embedded medullae. The PTA and PAS stains were abolished by acetylation, restored by saponification, unchanged by methylation, and greatly diminished by sulfation. In ultrathin sections of GMA- or Araldite- embedded medullae incubated with colloidal iron according to various techniques, the cell coat and lysosomes of both cell types were stained, unlike all the other cytoplasmic organelles. These results indicate that A granules and the Golgi complex of A cells, unlike the same structures in N cells, are rich in glycoproteins which are probably not acidic. PMID:47862

Drug loading into beta-cyclodextrin granules using a supercritical fluid process for improved drug dissolution.

PubMed

Hussein, Khaled; Türk, Michael; Wahl, Martin A

2008-03-03

To improve dissolution properties of drugs, a supercritical fluid (SCF) technique was used to load these drugs into a solid carrier. In this study, granules based on beta-cyclodextrin (betaCD) were applied as a carrier for poor water-soluble drug and loaded with a model drug (ibuprofen) using two different procedures: controlled particle deposition (CPD), SCF process and solution immersion (SI) as a conventional method for comparison. Using the CPD technique, 17.42+/-2.06wt.% (n=3) ibuprofen was loaded into betaCD-granules, in contrast to only 3.8+/-0.15wt.% (n=3) in the SI-product. The drug loading was confirmed as well by reduction of the BET surface area for the CPD-product (1.134+/-0.07m(2)/g) compared to the unloaded-granules (1.533+/-0.031m(2)/g). Such a reduction was not seen in the SI-product (1.407+/-0.048m(2)/g). The appearance of an endothermic melting peak at 77 degrees C and X-ray patterns representing ibuprofen in drug-loaded granules can be attributed to the amount of ibuprofen loaded in its crystalline form. A significant increase in drug dissolution was achieved by either drug-loading procedures compared to the unprocessed ibuprofen. In this study, the CPD technique, a supercritical fluid process avoiding the use of toxic or organic solvents was successfully applied to load drug into solid carriers, thereby improving the water-solubility of the drug.

Polyhydroxyalkanoate recovery and effect of in situ extracellular polymeric substances removal from aerobic granules.

PubMed

Gobi, K; Vadivelu, V M

2015-01-01

Polyhydroxyalkanoate (PHA) recovery from aerobic granules was investigated using four cell digestion agents, namely, sodium hypochlorite, sodium hydroxide, acetone and sodium chloride. Simultaneously, the removal of extracellular polymeric substances (EPS) and its effect on PHA yield were investigated. The highest PHA recovery yield was obtained using sodium hypochlorite, accounting for 89% cell dry weight (CDW). The highest PHA was recovered after the sodium hypochlorite completely removed the EPS from the aerobic granules. The average molecular weight (Mw) of the PHA recovered using sodium hypochlorite was 5.31 × 10(5)g/mol with only 1.8% molecular weight degradation. The energy and duration analysis for PHA recovery revealed that the sodium hypochlorite method required the least amount of energy and time at 0.0561 MJ/g PHA and 26 h, respectively. The PHA that was recovered was a P3(HB-co-HV) co-polymer. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thermal insulation for high temperature microwave sintering operations and method thereof

DOEpatents

Holcombe, Cressie E.; Dykes, Norman L.; Morrow, Marvin S.

1995-01-01

Superior microwave transparent thermal insulations for high temperature microwave sintering operations were prepared. One embodiment of the thermal insulation comprises granules of boron nitride coated with a very thin layer of glassy carbon made by preparing a glassy carbon precursor and blending it with boron nitride powder to form a mixture. The blended mixture is granulated to form a grit which is dried and heated to form the granules of boron nitride coated with a glassy carbon. Alternatively, grains of glassy carbon are coated with boron nitride by blending a mixture of a slurry comprising boron nitride, boric acid binder, and methyl alcohol with glassy carbon grains to form a blended mixture. The blended mixture is dried to form grains of glassy carbon coated with boron nitride. In addition, a physical mixture of boron nitride powder and glassy carbon grains has also been shown to be an excellent thermal insulation material for microwave processing and sintering.

Method of preparing thermal insulation for high temperature microwave sintering operations

DOEpatents

Holcombe, Cressie E.; Dykes, Norman L.; Morrow, Marvin S.

1996-01-01

Superior microwave transparent thermal insulations for high temperature microwave sintering operations were prepared. One embodiment of the thermal insulation comprises granules of boron nitride coated with a very thin layer of glassy carbon made by preparing a glassy carbon precursor and blending it with boron nitride powder to form a mixture. The blended mixture is granulated to form a grit which is dried and heated to form the granules of boron nitride coated with a glassy carbon. Alternatively, grains of glassy carbon are coated with boron nitride by blending a mixture of a slurry comprising boron nitride, boric acid binder, and methyl alcohol with glassy carbon grains to form a blended mixture. The blended mixture is dried to form grains of glassy carbon coated with boron nitride. In addition, a physical mixture of boron nitride powder and glassy carbon grains has also been shown to be an excellent thermal insulation material for microwave processing and sintering.

CERES Search and Subset Tool

Atmospheric Science Data Center

2016-06-24

... data granules using a high resolution spatial metadata database and directly accessing the archived data granules. Subset results are ... data granules using a high resolution spatial metadata database and directly accessing the archived data granules. Subset results are ...

Rule Extracting based on MCG with its Application in Helicopter Power Train Fault Diagnosis

NASA Astrophysics Data System (ADS)

Wang, M.; Hu, N. Q.; Qin, G. J.

2011-07-01

In order to extract decision rules for fault diagnosis from incomplete historical test records for knowledge-based damage assessment of helicopter power train structure. A method that can directly extract the optimal generalized decision rules from incomplete information based on GrC was proposed. Based on semantic analysis of unknown attribute value, the granule was extended to handle incomplete information. Maximum characteristic granule (MCG) was defined based on characteristic relation, and MCG was used to construct the resolution function matrix. The optimal general decision rule was introduced, with the basic equivalent forms of propositional logic, the rules were extracted and reduction from incomplete information table. Combined with a fault diagnosis example of power train, the application approach of the method was present, and the validity of this method in knowledge acquisition was proved.

Injected mass deposition thresholds for lithium granule instigated triggering of edge localized modes on EAST

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunsford, R.; Sun, Zhen; Maingi, Rajesh

The ability of an injected lithium granule to promptly trigger an edge localized mode (ELM) has been established in multiple experiments. By horizontally injecting granules ranging in diameter from 200 microns to 1mm in diameter into the low field side of EAST H-mode discharges we have determined that granules with diameter > 600 microns are successful in triggering ELMs more than 95% of the time. Granules were radially injected from the outer midplane with velocities ~ 80 m/s into EAST upper-single null discharges with an ITER like tungsten monoblock divertor. ELM triggering was a prompt response to granule injection, andmore » for granules of a sufficient size there was no evidence of a "trigger lag" phenomenon as observed in full metal machines. We also demonstrated that the triggering efficiency decreased with granule size during dynamic size scans. These granules were individually tracked throughout their injection cycle in order to determine their efficacy at triggering an ELM. Furthermore, by simulating the granule injection with an experimentally benchmarked neutral gas shielding (NGS) model, the ablatant mass deposition required to promptly trigger an ELM is calculated and the fractional mass deposition is determined. Simulated 900 micron granules capable of triggering an ELM show a peaked mass deposition of 3.9 x 10 17 atoms per mm of penetration at a depth of approximately 5 cm past the separatrix.« less

The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG).

PubMed

Takasaki, Hiroshi; Yonemochi, Etsuo; Ito, Masanori; Wada, Koichi; Terada, Katsuhide

2015-01-01

The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met) using the moist aqueous granulation (MAG) process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone-vinyl acetate copolymer (Kollidon VA64 fine: VA64), polyvidone (Povidone K12: PVP), hydroxypropyl cellulose (HPC SSL SF: HPC) and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC) were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API). HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water) and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance.

The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG)

PubMed Central

Takasaki, Hiroshi; Yonemochi, Etsuo; Ito, Masanori; Wada, Koichi; Terada, Katsuhide

2015-01-01

The aim of this study was to evaluate binders to improve the flowability of granulates and compactibility of Metformin HCL (Met) using the moist aqueous granulation (MAG) process. The effect of the binder moisture content on granulate and tablet quality was also evaluated. Vinylpyrrolidone–vinyl acetate copolymer (Kollidon VA64 fine: VA64), polyvidone (Povidone K12: PVP), hydroxypropyl cellulose (HPC SSL SF: HPC) and hydroxypropyl methylcellulose (Methocel E5 LV: HPMC) were evaluated as binders. These granulates, except for HPMC, had a lower yield pressure than Met active pharmaceutical ingredient (API). HPMC Met was not sufficiently granulated with low water volume. No problems were observed with the VA64 Met granulates during the tableting process. However, HPC Met granulates had a bowl-forming tendency, and PVP Met granulates had the tendency to stick during the tableting process. These bowl-forming and sticking tendencies may have been due to the low moisture absorbency of HPC and the high volume of bound water of PVP, respectively. VA64 Met granulates had the highest ambient moisture content (bulk water, bound water) and moisture absorbency. It was concluded that the type of binder used for the Met MAG process has an impact on granulate flow and compactibility, as well as moisture absorbency and maintenance of moisture balance. PMID:26779418

Impact of functionalized particle structure on roll compaction/dry granulation and tableting of calcium carbonate.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-06-10

The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO 3 ) was investigated. Therefore, a milled grade of CaCO 3 was compared to different binary mixtures of milled and functionalized CaCO 3 . Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force and granule size on tablet tensile strength was evaluated. Adding functionalized particles drastically influenced the granulation and tableting behavior of CaCO 3 . Increasing proportions increased the ribbon porosity and granule size. Tensile strength of tablets from powder mixtures and granules was increased as well. Nevertheless, adding functionalized CaCO 3 led to a loss in tabletability induced by a previous compaction step to an extent depending on its proportion in the formulation. A clear influence of the particle morphology on granulation and tableting behavior was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. Adding functionalized CaCO 3 to a mixture, even in small amounts, seemed to be beneficial to increase granule size and tablet strength. Copyright © 2018 Elsevier B.V. All rights reserved.

Injected mass deposition thresholds for lithium granule instigated triggering of edge localized modes on EAST

DOE PAGES

Lunsford, R.; Sun, Zhen; Maingi, Rajesh; ...

2017-12-19

The ability of an injected lithium granule to promptly trigger an edge localized mode (ELM) has been established in multiple experiments. By horizontally injecting granules ranging in diameter from 200 microns to 1mm in diameter into the low field side of EAST H-mode discharges we have determined that granules with diameter > 600 microns are successful in triggering ELMs more than 95% of the time. Granules were radially injected from the outer midplane with velocities ~ 80 m/s into EAST upper-single null discharges with an ITER like tungsten monoblock divertor. ELM triggering was a prompt response to granule injection, andmore » for granules of a sufficient size there was no evidence of a "trigger lag" phenomenon as observed in full metal machines. We also demonstrated that the triggering efficiency decreased with granule size during dynamic size scans. These granules were individually tracked throughout their injection cycle in order to determine their efficacy at triggering an ELM. Furthermore, by simulating the granule injection with an experimentally benchmarked neutral gas shielding (NGS) model, the ablatant mass deposition required to promptly trigger an ELM is calculated and the fractional mass deposition is determined. Simulated 900 micron granules capable of triggering an ELM show a peaked mass deposition of 3.9 x 10 17 atoms per mm of penetration at a depth of approximately 5 cm past the separatrix.« less

Identification of human cysteine-rich secretory protein 3 (CRISP-3) as a matrix protein in a subset of peroxidase-negative granules of neutrophils and in the granules of eosinophils.

PubMed

Udby, Lene; Calafat, Jero; Sørensen, Ole E; Borregaard, Niels; Kjeldsen, Lars

2002-09-01

Cysteine-rich secretory protein 3 (CRISP-3; also known as SGP28) was originally discovered in human neutrophilic granulocytes. We have recently developed a sensitive sandwich enzyme-linked immunosorbent assay for CRISP-3 and demonstrated the presence of CRISP-3 in exocrine secretions. To investigate the subcellular localization and mobilization of CRISP-3 in human neutrophils, we performed subcellular fractionation of resting and activated neutrophils on three-layer Percoll density gradients, release-studies of granule proteins in response to different secretagogues, and double-labeling immunogold electron microscopy. CRISP-3 was found to be localized in a subset of granules with overlapping characteristics of specific and gelatinase granules and mobilized accordingly, thus confirming the hypothesis that peroxidase-negative granules exist as a continuum from specific to gelatinase granules regarding protein content and mobilization. CRISP-3 was found to be a matrix protein, which is stored in granules as glycosylated and as unglycosylated protein. The subcellular distribution of the two forms of CRISP-3 was identical. In addition, CRISP-3 was found as a granule protein in eosinophilic granulocytes. The presence of CRISP-3 in peroxidase-negative granules of neutrophils, in granules of eosinophils, and in exocrine secretions indicates a role in the innate host defense.

Aspergillus oryzae AoSO is a novel component of stress granules upon heat stress in filamentous fungi.

PubMed

Huang, Hsiang-Ting; Maruyama, Jun-ichi; Kitamoto, Katsuhiko

2013-01-01

Stress granules are a type of cytoplasmic messenger ribonucleoprotein (mRNP) granule formed in response to the inhibition of translation initiation, which typically occurs when cells are exposed to stress. Stress granules are conserved in eukaryotes; however, in filamentous fungi, including Aspergillus oryzae, stress granules have not yet been defined. For this reason, here we investigated the formation and localization of stress granules in A. oryzae cells exposed to various stresses using an EGFP fusion protein of AoPab1, a homolog of Saccharomyces cerevisiae Pab1p, as a stress granule marker. Localization analysis showed that AoPab1 was evenly distributed throughout the cytoplasm under normal growth conditions, and accumulated as cytoplasmic foci mainly at the hyphal tip in response to stress. AoSO, a homolog of Neurospora crassa SO, which is necessary for hyphal fusion, colocalized with stress granules in cells exposed to heat stress. The formation of cytoplasmic foci of AoSO was blocked by treatment with cycloheximide, a known inhibitor of stress granule formation. Deletion of the Aoso gene had effects on the formation and localization of stress granules in response to heat stress. Our results suggest that AoSO is a novel component of stress granules specific to filamentous fungi. The authors would specially like to thank Hiroyuki Nakano and Kei Saeki for generously providing experimental and insightful opinions.

Behavior of hollow balls containing granules bouncing repeatedly off the ground

NASA Astrophysics Data System (ADS)

Hu, Min; Mu, Qing-song; Luo, Ning; Li, Gang; Peng, Ning-bo

2013-07-01

An experimental study of the behavior of hollow balls filled with some granules (mung beans or millets) bouncing repeatedly off a static flat horizontal surface is presented. We observed that the bounce number of the ball is limited and decreases regularly with an increasing number of granules. Moreover, for two balls containing a different kind of granules, their bounce numbers are basically equal when the two balls have the same mass of granules. While there is no clear relationship between the first rebound height of one ball and the number of granules, there appears an exponential decay of the second rebound height with an increase of the granule number. Furthermore, a two-dimensional numerical model has been created to find out the law of the ball's rebound height and the dissipation law of the granule nested system. A generalized prediction equation to reasonably explain the law of the bounce number has also been proposed.

An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment.

PubMed

Mangwandi, Chirangano; Adams, Michael J; Hounslow, Michael J; Salman, Agba D

2012-05-10

Being able to predict the properties of granules from the knowledge of the process and formulation variables is what most industries are striving for. This research uses experimental design to investigate the effect of process variables and formulation variables on mechanical properties of pharmaceutical granules manufactured from a classical blend of lactose and starch using hydroxypropyl cellulose (HPC) as the binder. The process parameters investigated were granulation time and impeller speed whilst the formulation variables were starch-to-lactose ratio and HPC concentration. The granule properties investigated include granule packing coefficient and granule strength. The effect of some components of the formulation on mechanical properties would also depend on the process variables used in granulation process. This implies that by subjecting the same formulation to different process conditions results in products with different properties. Copyright © 2012 Elsevier B.V. All rights reserved.

Distribution of binder in granules produced by means of twin screw granulation.

PubMed

Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen; Vervaet, Chris; Remon, Jean Paul; Strachan, Clare; Rades, Thomas; De Beer, Thomas

2014-02-28

According to the quality by design principle processes may not remain black-boxes and full process understanding is required. The granule size distribution of granules produced via twin screw granulation is often found to be bimodal. The aim of this study was to gain a better understanding of binder distribution within granules produced via twin screw granulation in order to investigate if an inhomogeneous spread of binder is causing this bimodal size distribution. Theophylline-lactose-polyvinylpyrrolidone K30 (PVP) (30-67.5-2.5%, w/w) was used as a model formulation. The intra-granular distribution of PVP was evaluated by means of hyperspectral coherent anti-Stokes Raman scattering (CARS) microscopy. For the evaluated formulation, no PVP rich zones were detected when applying a lateral spatial resolution of 0.5 μm, indicating that PVP is homogenously distributed within the granules. Copyright © 2013 Elsevier B.V. All rights reserved.

Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation

NASA Technical Reports Server (NTRS)

Krichevsky, A. M.; Kosik, K. S.

2001-01-01

RNA granules are a macromolecular structure observed in neurons, where they serve as motile units that translocate mRNAs. Isolated RNA granules are highly enriched in Staufen protein and ultrastructurally contain densely packed clusters of ribosomes. With depolarization, many mRNAs, including those involved in plasticity, rapidly shift from the RNA granule fraction to polysomes. Depolarization reorganizes granules and induces a less compact organization of their ribosomes. RNA granules are not translationally competent, as indicated by the failure to incorporate radioactive amino acids and the absence of eIF4E, 4G, and tRNAs. We concluded that RNA granules are a local storage compartment for mRNAs under translational arrest but are poised for release to actively translated pools. Local release of mRNAs and ribosomes from granules may serve as a macromolecular mechanism linking RNA localization to translation and synaptic plasticity.

The converse magnetoelectric coupling in asymmetric granule/matrix composite film with Ni/PZT component

NASA Astrophysics Data System (ADS)

Chen, Bo; Su, Ning-Ning; Cui, Wen-Li; Yan, Shi-Nong

2018-04-01

In this work, a type of asymmetric granule/matrix composite film is designed, where the Ni granule is dispersed in PZT matrix, meanwhile the top and bottom electrode is constituted by Au and SRO respectively. Predicted through the electrostatic screening model and mean field approximation, considerable electrostatic charge is induced on Ni granule surface by ferroelectric PZT polarization. Predicted through the spin splitting model and spherical shell approximation, both the magnetization and magnetic anisotropy of Ni granule are modulated by ferroelectric PZT polarization. As the volume fraction of Ni granule is increased, the electric modulation of magnetization and magnetic anisotropy is reduced and enhanced respectively. As the dimension of granule/matrix composite is varied, such modulation is retained. Due to the large area-volume ratio of nano-granule, this work benefits to realize the converse magnetoelectric coupling in nanoscale.

Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

PubMed

Aoki, Hajime; Iwao, Yasunori; Mizoguchi, Midori; Noguchi, Shuji; Itai, Shigeru

2015-05-01

In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated Helicobacter pylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone. Copyright © 2015 Elsevier B.V. All rights reserved.

The effect of B{sub 2}O{sub 3} flux on growth NLBCO superconductor by solid state reaction and wet-mixing methods

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suharta, W. G., E-mail: wgsuharta@gmail.com; Wendri, N.; Ratini, N.

The synthesis of B{sub 2}O{sub 3} flux substituted NLBCO superconductor NdBa{sub 1.75}La{sub 0.25}Cu{sub 3}O{sub 7-∂} has been done using solid state reaction and wet-mixing methods in order to obtain homogeneous crystals and single phase. From DTA/TGA characteritations showed the synthesis process by wet-mixing requires a lower temperature than the solid state reaction in growing the superconductor NdBa{sub 1.75}La{sub 0.25}Cu{sub 3}O{sub 7-∂}. Therefore, in this research NdBa{sub 1.75}La{sub 0.25}Cu{sub 3}O{sub 7-∂} sample calcinated at 650°C for wet-mixing method and 820°C for solid state reaction methods. The all samples was sintered at 950°C for ten hours. Crystallinity of the sample was confirmedmore » using X-ray techniques and generally obtained sharp peaks that indicates the sample already well crystallized. Search match analyses for diffraction data gave weight fractions of impurity phase of the solid state reaction method higher than wet-mixing method. In this research showed decreasing the price of the lattice parameter about 1% with the addition of B{sub 2}O{sub 3} flux for the both synthesis process and 2% of wet mixing process for all samples. Characterization using scanning electron microscopy (SEM) showed the distribution of crystal zise for wet-mixing method more homogeneous than solid state reaction method, with he grain size of samples is around 150–250 nm. The results of vibrating sample magnetometer (VSM) showed the paramagnetic properties for all samples.« less

Differential compaction behaviour of roller compacted granules of clopidogrel bisulphate polymorphs.

PubMed

Khomane, Kailas S; Bansal, Arvind K

2014-09-10

In the present work, in-die and out-of-die compaction behaviour of dry-granulated powders of clopidogrel bisulphate (CLP) polymorphs, form I and form II, was investigated using a fully instrumented rotary tablet press. Each polymorph was compacted at three different roller pressures [70.3 (S1), 105.5 (S2) and 140.6 (S3)kgf/cm(2)], and obtained granules were characterized for their physico-mechanical properties. Compaction data were analyzed for out-of-die compressibility, tabletability and compactibility profiles, and in-die Heckel, Kawakita and Walker analysis. The roller compacted granules of both forms showed markedly different tabletting behaviour. Roller pressure exhibited a trend on compaction behaviour of form I granules, whereas, in case of form II, the effect was insignificant. Tabletability of the six granule batches follows the order; I_S1>I_S2>I_S3>II_S1≈II_S2≈II_S3. In case of form I, the reduced tabletability of the granules compacted at higher roller pressure was attributed to the decreased compressibility and plastic deformation. This was confirmed by compressibility plot and various mathematical parameters derived from Heckel (Py), Kawakita (1/b) and Walker (W) equations. The reduced tabletability of form I granules was due to 'granule hardening' during roller compaction. On the other hand, insignificant effect of roller compaction on tabletting behaviour of form II granules was attributed to brittle fragmentation. The extensive fragmentation of granules offered new 'clean' surfaces and higher contact points that negated the effect of granule hardening. Copyright © 2014 Elsevier B.V. All rights reserved.

A Quasi-Periodic Linear Feeder for the Impurity Granular Injection on DIII-D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nagy, Alex; Bortolon, A.; Brown, W.

Injection of solid nonfuel pellets has been actively used as a tool for pacing and mitigation of edge localized modes (ELMs). In DIII-D, effective ELM pacing has been demonstrated by the high-frequency injection of lithium and carbon submillimeter spheres, using the impurity granule injector (IGI). This device injects granules into the plasma at speeds up to 150 m/s, through impact with a rotating impeller. In the IGI, high-frequency granule delivery was accomplished through a vibrational granule dropper, in which high time-average rates are obtained at the cost of lack of period control. Here, we present a new in-line granule feeder,more » capable of delivering granules of size 0.2-2 mm with no restriction of material properties, at quasi-periodic rates of up to 150 Hz, for 0.7-mm diameter lithium granules (600 Hz using 0.3-mm granules). The new dropper mechanism combines two piezo-in-line units; one which feeds the impeller and one which circulates granules that are filtered out of the feeder path. A remotely adjustable filter eliminates granules that are stacked, oversized, or side by side allowing the formation of a single moving granule injection line. The granules fall off the in-line feeder exit one at a time, achieving a quasi-periodic delivery rate proportional to the exit speed. At higher rates, the periodicity deteriorates. This behavior was studied using high-speed cameras and electrostatic measurements, and it was found that at drop rates <60 Hz, the granule delivery period has a variation of ±25% which appears to be caused by gaps which develop in the last centimeter of the injection line, as granules exit off the moving track. The linear feeder concept is robust against bridge instabilities and clogging issues, thanks to the simple diverter filter and constant recirculation of granules. Furthermore, the open-top design of the device facilitates refilling the device from separate reservoirs and has easy access for directly monitoring operation and adjustment. This paper describes the details of the in-line feeder design, along with several design iterations. The goal is a robust in-vacuum mechanism that can deliver granule flow ranging from a single particle to a line of particles at 150 per second, using different sizes and materials from the same apparatus.« less

A Quasi-Periodic Linear Feeder for the Impurity Granular Injection on DIII-D

DOE PAGES

Nagy, Alex; Bortolon, A.; Brown, W.; ...

2018-04-10

Injection of solid nonfuel pellets has been actively used as a tool for pacing and mitigation of edge localized modes (ELMs). In DIII-D, effective ELM pacing has been demonstrated by the high-frequency injection of lithium and carbon submillimeter spheres, using the impurity granule injector (IGI). This device injects granules into the plasma at speeds up to 150 m/s, through impact with a rotating impeller. In the IGI, high-frequency granule delivery was accomplished through a vibrational granule dropper, in which high time-average rates are obtained at the cost of lack of period control. Here, we present a new in-line granule feeder,more » capable of delivering granules of size 0.2-2 mm with no restriction of material properties, at quasi-periodic rates of up to 150 Hz, for 0.7-mm diameter lithium granules (600 Hz using 0.3-mm granules). The new dropper mechanism combines two piezo-in-line units; one which feeds the impeller and one which circulates granules that are filtered out of the feeder path. A remotely adjustable filter eliminates granules that are stacked, oversized, or side by side allowing the formation of a single moving granule injection line. The granules fall off the in-line feeder exit one at a time, achieving a quasi-periodic delivery rate proportional to the exit speed. At higher rates, the periodicity deteriorates. This behavior was studied using high-speed cameras and electrostatic measurements, and it was found that at drop rates <60 Hz, the granule delivery period has a variation of ±25% which appears to be caused by gaps which develop in the last centimeter of the injection line, as granules exit off the moving track. The linear feeder concept is robust against bridge instabilities and clogging issues, thanks to the simple diverter filter and constant recirculation of granules. Furthermore, the open-top design of the device facilitates refilling the device from separate reservoirs and has easy access for directly monitoring operation and adjustment. This paper describes the details of the in-line feeder design, along with several design iterations. The goal is a robust in-vacuum mechanism that can deliver granule flow ranging from a single particle to a line of particles at 150 per second, using different sizes and materials from the same apparatus.« less

Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules

PubMed Central

Kroschwald, Sonja; Maharana, Shovamayee; Mateju, Daniel; Malinovska, Liliana; Nüske, Elisabeth; Poser, Ina; Richter, Doris; Alberti, Simon

2015-01-01

RNA-protein (RNP) granules have been proposed to assemble by forming solid RNA/protein aggregates or through phase separation into a liquid RNA/protein phase. Which model describes RNP granules in living cells is still unclear. In this study, we analyze P bodies in budding yeast and find that they have liquid-like properties. Surprisingly, yeast stress granules adopt a different material state, which is reminiscent of solid protein aggregates and controlled by protein disaggregases. By using an assay to ectopically nucleate RNP granules, we further establish that RNP granule formation does not depend on amyloid-like aggregation but rather involves many promiscuous interactions. Finally, we show that stress granules have different properties in mammalian cells, where they show liquid-like behavior. Thus, we propose that the material state of RNP granules is flexible and that the solid state of yeast stress granules is an adaptation to extreme environments, made possible by the presence of a powerful disaggregation machine. DOI: http://dx.doi.org/10.7554/eLife.06807.001 PMID:26238190

Concerted suppression of all starch branching enzyme genes in barley produces amylose-only starch granules

PubMed Central

2012-01-01

Background Starch is stored in higher plants as granules composed of semi-crystalline amylopectin and amorphous amylose. Starch granules provide energy for the plant during dark periods and for germination of seeds and tubers. Dietary starch is also a highly glycemic carbohydrate being degraded to glucose and rapidly absorbed in the small intestine. But a portion of dietary starch, termed “resistant starch” (RS) escapes digestion and reaches the large intestine, where it is fermented by colonic bacteria producing short chain fatty acids (SCFA) which are linked to several health benefits. The RS is preferentially derived from amylose, which can be increased by suppressing amylopectin synthesis by silencing of starch branching enzymes (SBEs). However all the previous works attempting the production of high RS crops resulted in only partly increased amylose-content and/or significant yield loss. Results In this study we invented a new method for silencing of multiple genes. Using a chimeric RNAi hairpin we simultaneously suppressed all genes coding for starch branching enzymes (SBE I, SBE IIa, SBE IIb) in barley (Hordeum vulgare L.), resulting in production of amylose-only starch granules in the endosperm. This trait was segregating 3:1. Amylose-only starch granules were irregularly shaped and showed peculiar thermal properties and crystallinity. Transgenic lines retained high-yield possibly due to a pleiotropic upregualtion of other starch biosynthetic genes compensating the SBEs loss. For gelatinized starch, a very high content of RS (65 %) was observed, which is 2.2-fold higher than control (29%). The amylose-only grains germinated with same frequency as control grains. However, initial growth was delayed in young plants. Conclusions This is the first time that pure amylose has been generated with high yield in a living organism. This was achieved by a new method of simultaneous suppression of the entire complement of genes encoding starch branching enzymes. We demonstrate that amylopectin is not essential for starch granule crystallinity and integrity. However the slower initial growth of shoots from amylose-only grains may be due to an important physiological role played by amylopectin ordered crystallinity for rapid starch remobilization explaining the broad conservation in the plant kingdom of the amylopectin structure. PMID:23171412

The design of free structure granular mappings: the use of the principle of justifiable granularity.

PubMed

Pedrycz, Witold; Al-Hmouz, Rami; Morfeq, Ali; Balamash, Abdullah

2013-12-01

The study introduces a concept of mappings realized in presence of information granules and offers a design framework supporting the formation of such mappings. Information granules are conceptually meaningful entities formed on a basis of a large number of experimental input–output numeric data available for the construction of the model. We develop a conceptually and algorithmically sound way of forming information granules. Considering the directional nature of the mapping to be formed, this directionality aspect needs to be taken into account when developing information granules. The property of directionality implies that while the information granules in the input space could be constructed with a great deal of flexibility, the information granules formed in the output space have to inherently relate to those built in the input space. The input space is granulated by running a clustering algorithm; for illustrative purposes, the focus here is on fuzzy clustering realized with the aid of the fuzzy C-means algorithm. The information granules in the output space are constructed with the aid of the principle of justifiable granularity (being one of the underlying fundamental conceptual pursuits of Granular Computing). The construct exhibits two important features. First, the constructed information granules are formed in the presence of information granules already constructed in the input space (and this realization is reflective of the direction of the mapping from the input to the output space). Second, the principle of justifiable granularity does not confine the realization of information granules to a single formalism such as fuzzy sets but helps form the granules expressed any required formalism of information granulation. The quality of the granular mapping (viz. the mapping realized for the information granules formed in the input and output spaces) is expressed in terms of the coverage criterion (articulating how well the experimental data are “covered” by information granules produced by the granular mapping for any input experimental data). Some parametric studies are reported by quantifying the performance of the granular mapping (expressed in terms of the coverage and specificity criteria) versus the values of a certain parameters utilized in the construction of output information granules through the principle of justifiable granularity. The plots of coverage–specificity dependency help determine a knee point and reach a sound compromise between these two conflicting requirements imposed on the quality of the granular mapping. Furthermore, quantified is the quality of the mapping with regard to the number of information granules (implying a certain granularity of the mapping). A series of experiments is reported as well.

Application of the thiocarbohydrazide method for vicinal glycol group detection to the study of gastric mucosa endocrine cells.

PubMed

Lefranc, G; Chung, Y T; Barrière, P; Pradal, G

1980-01-01

The thiocarbohydrazide-silver proteinate (TCH SP) method was applied to the study of cat, rabbit and mouse gastric mucosa endocrine cells. After 24-h treatment with thiocarbohydrazide (TCH), glycogen was seen in the hyaloplasm of X, D, P, A and O cells but not in EC, EC-like or D1 cells. With flotation times as short as 30 to 40 min glycogen was readily detected in X cells. Secretory granules of EC cells were constantly stained, while those of D1 cells failed to react. In most experiments granules of X, A and O cells showed peripheral "staining", while in others staining of variable intensity affected the entire granular cross-section in X, D and P cells. With 72-h exposure to TCH, EC and EC-like cells showed particles resembling glycogen, even staining or only peripheral staining of certain EC cell granules. From the results of this and previous studies, EC cell staining is believed to be due wholly or partly, according to exposure times, to the action of silver proteinate, while that of certain non-EC cells is probably a specific indicator of complexed carbohydrates.

A new low-cost negative-pressure wound therapy versus a commercially available therapy device widely used to treat complex traumatic injuries: a prospective, randomized, non-inferiority trial.

PubMed

Kamamoto, Fabio; Lima, Ana Lucia Munhoz; Rezende, Marcelo Rosa de; Mattar-Junior, Rames; Leonhardt, Marcos de Camargo; Kojima, Kodi Edson; Santos, Carla Chineze Dos

2017-12-01

Negative-pressure wound therapy has been widely adopted to reduce the complexity of treating a broad range of acute and chronic wounds. However, its cost is high. The objective of this study was to evaluate the following two different methods of negative-pressure wound therapy in terms of healing time: a low-cost method of negative-pressure wound therapy (a pressure stabilizer device connected to a hospital wall-vacuum system with a gauze-sealed dressing, USP) and the standard of care (vacuum-assisted closure, VAC). This is a randomized, controlled, non-inferiority, unblinded trial. Patients admitted with complex injuries to a trauma center in a public referral hospital who were indicated for orthopedic surgery were randomized to a USP or VAC group. The primary outcome was the time required to achieve a "ready for surgery condition", which was defined as a wound bed with healthy granulation tissue and without necrosis or purulent secretion. Wound bed area contraction, granulation tissue growth and the direct costs of the dressings were secondary outcomes. Variation in area and granulation tissue growth were essentially the same between the systems, and healing time was equal between the groups (p=0.379). In both systems, serial debridement increased wound area (p=0.934), and granulation tissue was also increased (p=0.408). The mean treatment cost was US$ 15.15 in the USP group and US$ 872.59 in the VAC group. For treating complex traumatic injuries, USP was non-inferior to and less expensive than VAC.

Docking is not a prerequisite but a temporal constraint for fusion of secretory granules.

PubMed

Kasai, Kazuo; Fujita, Takuji; Gomi, Hiroshi; Izumi, Tetsuro

2008-07-01

We examined secretory granule dynamics using total internal reflection fluorescence microscopy in normal pancreatic beta cells and their mutants devoid of Rab27a and/or its effector, granuphilin, which play critical roles in the docking and recruitment of insulin granules to the plasma membrane. In the early phase of glucose stimulation in wild-type cells, we observed marked fusion of granules recruited from a relatively distant area, in parallel with that from granules located underneath the plasma membrane. Furthermore, despite a lack of granules directly attached to the plasma membrane, both spontaneous and evoked fusion was increased in granuphilin-null cells. In addition to these granuphilin-null phenotypes, Rab27a/granuphilin doubly deficient cells showed the decreases in granules located next to the docked area and in fusion from granules near the plasma membrane in the early phase of glucose-stimulated secretion, similar to Rab27a-mutated cells. Thus, the two proteins play nonoverlapping roles in insulin exocytosis: granuphilin acts on the granules underneath the plasma membrane, whereas Rab27a acts on those in a more distal area. These findings demonstrate that, in contrast to our conventional understanding, stable attachment of secretory granules to the plasma membrane is not prerequisite but temporally inhibitory for both spontaneous and evoked fusion.

TDP-43 is directed to stress granules by sorbitol, a novel physiological osmotic and oxidative stressor.

PubMed

Dewey, Colleen M; Cenik, Basar; Sephton, Chantelle F; Dries, Daniel R; Mayer, Paul; Good, Shannon K; Johnson, Brett A; Herz, Joachim; Yu, Gang

2011-03-01

TDP-43, or TAR DNA-binding protein 43, is a pathological marker of a spectrum of neurodegenerative disorders, including amyotrophic lateral sclerosis and frontotemporal lobar degeneration with ubiquitin-positive inclusions. TDP-43 is an RNA/DNA-binding protein implicated in transcriptional and posttranscriptional regulation. Recent work also suggests that TDP-43 associates with cytoplasmic stress granules, which are transient structures that form in response to stress. In this study, we establish sorbitol as a novel physiological stressor that directs TDP-43 to stress granules in Hek293T cells and primary cultured glia. We quantify the association of TDP-43 with stress granules over time and show that stress granule association and size are dependent on the glycine-rich region of TDP-43, which harbors the majority of pathogenic mutations. Moreover, we establish that cells harboring wild-type and mutant TDP-43 have distinct stress responses: mutant TDP-43 forms significantly larger stress granules, and is incorporated into stress granules earlier, than wild-type TDP-43; in striking contrast, wild-type TDP-43 forms more stress granules over time, but the granule size remains relatively unchanged. We propose that mutant TDP-43 alters stress granule dynamics, which may contribute to the progression of TDP-43 proteinopathies.

Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cameron, R.S.; Cameron, P.L.; Castle, J.D.

1986-10-01

A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pImore » and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion.« less

Critical evaluation of root causes of the reduced compactability after roll compaction/dry granulation.

PubMed

Mosig, Johanna; Kleinebudde, Peter

2015-03-01

The influence of lubrication and particle size on the reduced compactability after dry granulation was investigated. Powder cellulose, lactose, magnesium carbonate, and two types of microcrystalline cellulose were roll compacted, granulated, and sieved into particle fractions. Particle fractions were compressed into tablets using internal and external lubrication. Internal lubrication resulted in an overlubrication of the granule material compared with the powder material. This resulted in extraordinary high reduction of compactability after dry granulation for lubricant-sensitive materials. The granule size can cause differences in strength, whereby the degree of this effect was material dependent. The loss in strength with increasing compaction force was comparable for different particles sizes of one material, suggesting a change in material properties independently of the size. Granule hardening could be one reason as for higher compaction forces the integrity of the granule structure survived the compression step. The results demonstrated that granule lubrication mainly influence the degree of the reduced compactability after dry granulation and must be considered for the evaluation of mechanism for this phenomenon. Hardening of the material as well as size enlargement will cause the loss in strength after recompression, but the influence of both depends strongly on the material. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation.

PubMed

Grote, Simon; Kleinebudde, Peter

2018-05-29

The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.

Joint Effects of Granule Size and Degree of Substitution on Octenylsuccinated Sweet Potato Starch Granules As Pickering Emulsion Stabilizers.

PubMed

Li, Jinfeng; Ye, Fayin; Lei, Lin; Zhou, Yun; Zhao, Guohua

2018-05-02

The granules of sweet potato starch were size fractionated into three portions with significantly different median diameters ( D 50 ) of 6.67 (small-sized), 11.54 (medium-sized), and 16.96 μm (large-sized), respectively. Each portion was hydrophobized at the mass-based degrees of substitution (DS m ) of approximately 0.0095 (low), 0.0160 (medium), and 0.0230 (high). The Pickering emulsion-stabilizing capacities of modified granules were tested, and the resultant emulsions were characterized. The joint effects of granule size and DS m on emulsifying capacity (EC) were investigated by response surface methodology. For small-, medium-, and large-sized fractions, their highest emulsifying capacities are comparable but, respectively, encountered at high (0.0225), medium (0.0158), and low (0.0095) DS m levels. The emulsion droplet size increased with granule size, and the number of freely scattered granules in emulsions decreased with DS m . In addition, the term of surface density of the octenyl succinic group (SD -OSG ) was first proposed for modified starch granules, and it was proved better than DS m in interpreting the emulsifying capacities of starch granules with varying sizes. The present results implied that, as the particulate stabilizers, the optimal DS m of modified starch granules is size specific.

Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor

PubMed Central

Bin, Zhang; Bin, Xue; Zhigang, Qiu; Zhiqiang, Chen; Junwen, Li; Taishi, Gong; Wenci, Zou; Jingfeng, Wang

2015-01-01

Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3−-N could be removed or reduced, some amount of NO2−-N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy. PMID:26257096

Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor.

PubMed

Bin, Zhang; Bin, Xue; Zhigang, Qiu; Zhiqiang, Chen; Junwen, Li; Taishi, Gong; Wenci, Zou; Jingfeng, Wang

2015-08-10

Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3(-)-N could be removed or reduced, some amount of NO2(-)-N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy.

Texture Analysis of Poly-Adenylated mRNA Staining Following Global Brain Ischemia and Reperfusion

PubMed Central

Szymanski, Jeffrey J.; Jamison, Jill T.; DeGracia, Donald J.

2011-01-01

Texture analysis provides a means to quantify complex changes in microscope images. We previously showed that cytoplasmic poly-adenylated mRNAs form mRNA granules in post-ischemic neurons and that these granules correlated with protein synthesis inhibition and hence cell death. Here we utilized the texture analysis software MaZda to quantify mRNA granules in photomicrographs of the pyramidal cell layer of rat hippocampal region CA3 around 1 hour of reperfusion after 10 min of normothermic global cerebral ischemia. At 1 hour reperfusion, we observed variations in the texture of mRNA granules amongst samples that were readily quantified by texture analysis. Individual sample variation was consistent with the interpretation that animal-to-animal variations in mRNA granules reflected the time-course of mRNA granule formation. We also used texture analysis to quantify the effect of cycloheximide, given either before or after brain ischemia, on mRNA granules. If administered before ischemia, cycloheximide inhibited mRNA granule formation, but if administered after ischemia did not prevent mRNA granulation, indicating mRNA granule formation is dependent on dissociation of polysomes. We conclude that texture analysis is an effective means for quantifying the complex morphological changes induced in neurons by brain ischemia and reperfusion. PMID:21477879

Spatial patterning of P granules by RNA-induced phase separation of the intrinsically-disordered protein MEG-3

PubMed Central

Smith, Jarrett; Calidas, Deepika; Schmidt, Helen; Lu, Tu; Rasoloson, Dominique; Seydoux, Geraldine

2016-01-01

RNA granules are non-membrane bound cellular compartments that contain RNA and RNA binding proteins. The molecular mechanisms that regulate the spatial distribution of RNA granules in cells are poorly understood. During polarization of the C. elegans zygote, germline RNA granules, called P granules, assemble preferentially in the posterior cytoplasm. We present evidence that P granule asymmetry depends on RNA-induced phase separation of the granule scaffold MEG-3. MEG-3 is an intrinsically disordered protein that binds and phase separates with RNA in vitro. In vivo, MEG-3 forms a posterior-rich concentration gradient that is anti-correlated with a gradient in the RNA-binding protein MEX-5. MEX-5 is necessary and sufficient to suppress MEG-3 granule formation in vivo, and suppresses RNA-induced MEG-3 phase separation in vitro. Our findings suggest that MEX-5 interferes with MEG-3’s access to RNA, thus locally suppressing MEG-3 phase separation to drive P granule asymmetry. Regulated access to RNA, combined with RNA-induced phase separation of key scaffolding proteins, may be a general mechanism for controlling the formation of RNA granules in space and time. DOI: http://dx.doi.org/10.7554/eLife.21337.001 PMID:27914198

Denitrifying capability and community dynamics of glycogen accumulating organisms during sludge granulation in an anaerobic-aerobic sequencing batch reactor

NASA Astrophysics Data System (ADS)

Bin, Zhang; Bin, Xue; Zhigang, Qiu; Zhiqiang, Chen; Junwen, Li; Taishi, Gong; Wenci, Zou; Jingfeng, Wang

2015-08-01

Denitrifying capability of glycogen accumulating organisms (GAOs) has received great attention in environmental science and microbial ecology. Combining this ability with granule processes would be an interesting attempt. Here, a laboratory-scale sequencing batch reactor (SBR) was operated to enrich GAOs and enable sludge granulation. The results showed that the GAO granules were cultivated successfully and the granules had denitrifying capability. The batch experiments demonstrated that all NO3--N could be removed or reduced, some amount of NO2--N were accumulated in the reactor, and N2 was the main gaseous product. SEM analysis suggested that the granules were tightly packed with a large amount of tetrad-forming organisms (TFOs); filamentous bacteria served as the supporting structures for the granules. The microbial community structure of GAO granules was differed substantially from the inoculant conventional activated sludge. Most of the bacteria in the seed sludge grouped with members of Proteobacterium. FISH analysis confirmed that GAOs were the predominant members in the granules and were distributed evenly throughout the granular space. In contrast, PAOs were severely inhibited. Overall, cultivation of the GAO granules and utilizing their denitrifying capability can provide us with a new approach of nitrogen removal and saving more energy.

Non-destructive Determination of Disintegration Time and Dissolution in Immediate Release Tablets by Terahertz Transmission Measurements.

PubMed

Markl, Daniel; Sauerwein, Johanna; Goodwin, Daniel J; van den Ban, Sander; Zeitler, J Axel

2017-05-01

The aim of this study was to establish the suitability of terahertz (THz) transmission measurements to accurately measure and predict the critical quality attributes of disintegration time and the amount of active pharmaceutical ingredient (API) dissolved after 15, 20 and 25 min for commercial tablets processed at production scale. Samples of 18 batches of biconvex tablets from a production-scale design of experiments study into exploring the design space of a commercial tablet manufacturing process were used. The tablet production involved the process steps of high-shear wet granulation, fluid-bed drying and subsequent compaction. The 18 batches were produced using a 4 factor split plot design to study the effects of process changes on the disintegration time. Non-destructive and contactless terahertz transmission measurements of the whole tablets without prior sample preparation were performed to measure the effective refractive index and absorption coefficient of 6 tablets per batch. The disintegration time (R 2  = 0.86) and API dissolved after 15 min (R 2  = 0.96) linearly correlates with the effective refractive index, n eff , measured at terahertz frequencies. In contrast, no such correlation could be established from conventional hardness measurements. The magnitude of n eff represents the optical density of the sample and thus it reflects both changes in tablet porosity as well as granule density. For the absorption coefficient, α eff , we observed a better correlation with dissolution after 20 min (R 2  = 0.96) and a weaker correlation with disintegration (R 2  = 0.83) compared to n eff . The measurements of n eff and α eff provide promising predictors for the disintegration and dissolution time of tablets. The high penetration power of terahertz radiation makes it possible to sample a significant volume proportion of a tablet without any prior sample preparation. Together with the short measurement time (seconds), the potential to measure content uniformity and the fact that the method requires no chemometric models this technology shows clear promise to be established as a process analyser to non-destructively predict critical quality attributes of tablets.

RNA in development: how ribonucleoprotein granules regulate the life cycles of pathogenic protozoa.

PubMed

Kramer, Susanne

2014-01-01

Ribonucleoprotein (RNP) granules are important posttranscriptional regulators of messenger RNA (mRNA) fate. Several types of RNP granules specifically regulate gene expression during development of multicellular organisms and are commonly referred to as germ granules. The function of germ granules is not entirely understood and probably diverse, but it is generally agreed that one main function is posttranscriptional regulation of gene expression during early development, when transcription is silent. One example is the translational repression of maternally derived mRNAs in oocytes. Here, I hope to show that the need for regulation of gene expression by RNP granules is not restricted to animal development, but plays an equally important role during the development of pathogenic protozoa. Apicomplexa and Trypanosomatidae have complex life cycles with frequent host changes. The need to quickly adapt gene expression to a new environment as well as the ability to suppress translation to survive latencies is critical for successful completion of life cycles. Posttranscriptional gene regulation is not necessarily simpler in protozoa. Apicomplexa surprise with the presence of micro RNA (miRNAs) and upstream open reading frames (µORFs). Trypanosomes have an unusually large repertoire of different RNP granule types. A better understanding of RNP granules in protozoa may help to gain insight into the evolutionary origin of RNP granules: Trypanosomes for example have two types of granules with interesting similarities to animal germ granules. © 2013 John Wiley & Sons, Ltd.

Formation of tRNA granules in the nucleus of heat-induced human cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Miyagawa, Ryu; Department of Biological Science, Graduate School of Science, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8654; Mizuno, Rie

Highlights: Black-Right-Pointing-Pointer tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. Black-Right-Pointing-Pointer tRNAs form the unique granules in the nucleus. Black-Right-Pointing-Pointer tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules.more » Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA{sup Met} (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA{sup Met} was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.« less

Second Harmonic Generation Mediated by Aligned Water in Starch Granules.

PubMed

Cisek, Richard; Tokarz, Danielle; Krouglov, Serguei; Steup, Martin; Emes, Michael J; Tetlow, Ian J; Barzda, Virginijus

2014-12-26

The origin of second harmonic generation (SHG) in starch granules was investigated using ab initio quantum mechanical modeling and experimentally examined using polarization-in, polarization-out (PIPO) second harmonic generation microscopy. Ab initio calculations revealed that the largest contribution to the SHG signal from A- and B-type allomorphs of starch originates from the anisotropic organization of hydroxide and hydrogen bonds mediated by aligned water found in the polymers. The hypothesis was experimentally tested by imaging maize starch granules under various hydration and heat treatment conditions that alter the hydrogen bond network. The highest SHG intensity was found in fully hydrated starch granules, and heat treatment diminished the SHG intensity. The PIPO SHG imaging showed that dried starch granules have a much higher nonlinear optical susceptibility component ratio than fully hydrated granules. In contrast, deuterated starch granules showed a smaller susceptibility component ratio demonstrating that SHG is highly sensitive to the organization of the hydroxyl and hydrogen bond network. The polarization SHG imaging results of potato starch granules, representing starch allomorph B, were compared to those of maize starch granules representing allomorph A. The results showed that the amount of aligned water was higher in the maize granules. Nonlinear microscopy of starch granules provides evidence that varying hydration conditions leads to significant changes in the nonlinear susceptibility ratio as well as the SHG intensity, supporting the hypothesis from ab initio calculations that the dominant contribution to SHG is due to the ordered hydroxide and hydrogen bond network.

Digestion of Starch Granules from Maize, Potato and Wheat by Larvae of the the Yellow Mealworm, Tenebrio molitor and the Mexican Bean Weevil, Zabrotes subfasciatus

PubMed Central

Meireles, Elaine A.; Carneiro, Cíntia N. B.; DaMatta, Renato A.; Samuels, Richard I.; Silva, Carlos P.

2009-01-01

Scanning electron microscopy images were taken of starch granules from different sources following exposure in vivo and in vitro to gut α-amylases isolated from Tenebrio molitor L. (Coleoptera: Tenebrionidae) and Zabrotes subfasciatus Boheman (Coleoptera: Bruchidae). One α-amylase was isolated from whole larval midguts of T. molitor using non-denaturing SDS-PAGE, while two other α-amylase fractions were isolated from whole larval midguts of Z. subfasciatus using hydrophobic interaction chromatography., Digested starch granules from larvae fed on maize, potato or wheat were isolated from midgut contents. Combinations of starch granules with isolated α-amylases from both species showed similar patterns of granule degradation. In vitro enzymatic degradation of maize starch granules by the three different α-amylase fractions began by creating small holes and crater-like areas on the surface of the granules. Over time, these holes increased in number and area resulting in extensive degradation of the granule structure. Granules from potato did not show formation of pits and craters on their surface, but presented extensive erosion in their interior. For all types of starch, as soon as the interior of the starch granule was reached, the inner layers of amylose and amylopectin were differentially hydrolyzed, resulting in a striated pattern. These data support the hypothesis that the pattern of starch degradation depends more on the granule type than on the α-amylase involved. PMID:19619014

Wet refractivity tomography with an improved Kalman-Filter method

NASA Astrophysics Data System (ADS)

Cao, Yunchang; Chen, Yongqi; Li, Pingwha

2006-10-01

An improved retrieval method, which uses the solution with a Gaussian constraint as the initial state variables for the Kalman Filtering (KF) method, was developed to retrieve the wet refractivity profiles from slant wet delays (SWD) extracted by the double-differenced (DD) GPS method. The accuracy of the GPS-derived SWDs is also tested in this study against the measurements of a water vapor radiometer (WVR) and a weather model. It is concluded that the GPS-derived SWDs have similar accuracy to those measured with WVR and are much higher in quality than those derived from the weather model used. The developed method is used to retrieve the 3D wet refractivity distribution in the Hong Kong region. The retrieved profiles agree well with the radiosonde observations, with a difference of about 4 mm km-1 in the low levels. The accurate profiles obtained with this method are applicable in a number of meteorological applications.

[Study on spray-drier preparation technology of weitai granules using orthogonal experiments].

PubMed

Qu, Cai-Hong; Yang, Li; Chen, Zhi-Liang

2006-04-01

To screen preparation technique in order to raise the end-product and economical efficiency of spray-drier preparation technology of weitai granules. Newly Fluid-bed-spray-drier-granulation technique was adoped and taken extracting technique, temperature of exit and entry and the matching of accessories as inspecting factors, two levels of each factors, end-product and the water content of semi-finished weitai granules as inspecting marker, the best preparation technique of weitai granules was screened by orthogonal desing. Among the 3 factors, the matching of accessories was most notalbe (P < 0.01), next was the temperature of exit and entry (P < 0.05). However, the extracting technique was of little importance (P > 0.05). The optimum spray-drier granulation technique of weitai granules is A3B1C3.

Assessment of bacterial and structural dynamics in aerobic granular biofilms

PubMed Central

Weissbrodt, David G.; Neu, Thomas R.; Kuhlicke, Ute; Rappaz, Yoan; Holliger, Christof

2013-01-01

Aerobic granular sludge (AGS) is based on self-granulated flocs forming mobile biofilms with a gel-like consistence. Bacterial and structural dynamics from flocs to granules were followed in anaerobic-aerobic sequencing batch reactors (SBR) fed with synthetic wastewater, namely a bubble column (BC-SBR) operated under wash-out conditions for fast granulation, and two stirred-tank enrichments of Accumulibacter (PAO-SBR) and Competibacter (GAO-SBR) operated at steady-state. In the BC-SBR, granules formed within 2 weeks by swelling of Zoogloea colonies around flocs, developing subsequently smooth zoogloeal biofilms. However, Zoogloea predominance (37–79%) led to deteriorated nutrient removal during the first months of reactor operation. Upon maturation, improved nitrification (80–100%), nitrogen removal (43–83%), and high but unstable dephosphatation (75–100%) were obtained. Proliferation of dense clusters of nitrifiers, Accumulibacter, and Competibacter from granule cores outwards resulted in heterogeneous bioaggregates, inside which only low abundance Zoogloea (<5%) were detected in biofilm interstices. The presence of different extracellular glycoconjugates detected by fluorescence lectin-binding analysis showed the complex nature of the intracellular matrix of these granules. In the PAO-SBR, granulation occurred within two months with abundant and active Accumulibacter populations (56 ± 10%) that were selected under full anaerobic uptake of volatile fatty acids and that aggregated as dense clusters within heterogeneous granules. Flocs self-granulated in the GAO-SBR after 480 days during a period of over-aeration caused by biofilm growth on the oxygen sensor. Granules were dominated by heterogeneous clusters of Competibacter (37 ± 11%). Zoogloea were never abundant in biomass of both PAO- and GAO-SBRs. This study showed that Zoogloea, Accumulibacter, and Competibacter affiliates can form granules, and that the granulation mechanisms rely on the dominant population involved. PMID:23847600

Wet cooling towers: rule-of-thumb design and simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Leeper, Stephen A.

1981-07-01

A survey of wet cooling tower literature was performed to develop a simplified method of cooling tower design and simulation for use in power plant cycle optimization. The theory of heat exchange in wet cooling towers is briefly summarized. The Merkel equation (the fundamental equation of heat transfer in wet cooling towers) is presented and discussed. The cooling tower fill constant (Ka) is defined and values derived. A rule-of-thumb method for the optimized design of cooling towers is presented. The rule-of-thumb design method provides information useful in power plant cycle optimization, including tower dimensions, water consumption rate, exit air temperature,more » power requirements and construction cost. In addition, a method for simulation of cooling tower performance at various operating conditions is presented. This information is also useful in power plant cycle evaluation. Using the information presented, it will be possible to incorporate wet cooling tower design and simulation into a procedure to evaluate and optimize power plant cycles.« less

Detection and Analysis of the Quality of Ibuprofen Granules

NASA Astrophysics Data System (ADS)

Yu-bin, Ji; Xin, LI; Guo-song, Xin; Qin-bing, Xue

2017-12-01

The Ibuprofen Granules comprehensive quality testing to ensure that it is in accordance with the provisions of Chinese pharmacopoeia. With reference of Chinese pharmacopoeia, the Ibuprofen Granules is tested by UV, HPLC, in terms of grain size checking, volume deviation, weight loss on drying detection, dissolution rate detection, and quality evaluation. Results indicated that Ibuprofen Granules conform to the standards. The Ibuprofen Granules are qualified and should be permitted to be marketed.

Carbon, nitrogen and phosphorus removal mechanisms of aerobic granules.

PubMed

Sarma, Saurabh Jyoti; Tay, Joo-Hwa

2018-04-10

Aerobic granules are the potential tools to develop modern wastewater treatment technologies with improved nutrient removal efficiency. These granules have several promising advantages over conventional activated sludge-based wastewater treatment processes. This technology has the potential of reducing the infrastructure and operation costs of wastewater treatment by 25%, energy requirement by 30%, and space requirement by 75%. The nutrient removal mechanisms of aerobic granules are slightly different from that of the activated sludge. For instance, unlike activated sludge process, according to some reports, as high as 70% of the total phosphorus removed by aerobic granules were attributed to precipitation within the granules. Similarly, aerobic granule-based technology reduces the total amount of sludge produced during wastewater treatment. However, the reason behind this observation is unknown and it needs further explanations based on carbon and nitrogen removal mechanisms. Thus, as a part of the present review, a set of new hypotheses have been proposed to explain the peculiar nutrient removal mechanisms of the aerobic granules.

Native granule associated short chain length polyhydroxyalkanoate synthase from a marine derived Bacillus sp. NQ-11/A2.

PubMed

Prabhu, Nimali N; Santimano, Maria Celisa; Mavinkurve, Suneela; Bhosle, Saroj N; Garg, Sandeep

2010-01-01

A rapidly growing marine derived Bacillus sp. strain NQ-11/A2, identified as Bacillus megaterium, accumulated 61% polyhydroxyalkanoate by weight. Diverse carbon sources served as substrates for the accumulation of short chain length polyhydroxyalkanoate. Three to nine granules either single or attached as buds could be isolated intact from each cell. Maximum activity of polyhydroxyalkanoate synthase was associated with the granules. Granule-bound polyhydroxyalkanoate synthase had a K(m) of 7.1 x 10(-5) M for DL-beta-hydroxybutyryl-CoA. Temperature and pH optima for maximum activity were 30 degrees C and 7.0, respectively. Sodium ions were required for granule-bound polyhydroxyalkanoate synthase activity and inhibited by potassium. Granule-bound polyhydroxyalkanoate synthase was apparently covalently bound to the polyhydroxyalkanoate-core of the granules and affected by the chaotropic reagent urea. Detergents inhibited the granule-bound polyhydroxyalkanoate synthase drastically whilst glycerol and bovine serum albumin stabilized the synthase.

The Impact of Disintegrant Type, Surfactant, and API Properties on the Processability and Performance of Roller Compacted Formulations of Acetaminophen and Aspirin.

PubMed

Zhao, Junshu; Koo, Otilia; Pan, Duohai; Wu, Yongmei; Morkhade, Dinesh; Rana, Sandeep; Saha, Partha; Marin, Arturo

2017-09-01

In formulation development, certain excipients, even though used in small quantities, can have a significant impact on the processability and performance of the dosage form. In this study, three common disintegrants, croscarmellose sodium (CCS), crospovidone (xPVP), and sodium starch glycolate (SSG) as well as the surfactant sodium lauryl sulfate (SLS) were evaluated for their impact on the processability and performance of a typical dry granulation formulation. Two model compounds, the mechanically brittle and chemically inert acetaminophen and the mechanically ductile carboxylic acid aspirin, were used for the evaluation. It was found that the disintegrants were generally identical in their impact on the processability and little difference was observed in the granulation and compression processes. The exception is that when xPVP was used in the formulation of the brittle acetaminophen, lower compression forces were needed to reach the same tablet hardness, suggesting a binding effect of xPVP for such systems. In general, CCS and xPVP tend to provide slightly better disintegration than SSG. However, in the case of aspirin, a strong hydrogen bonding interaction between the carboxylic acid group of aspirin and the carbonyl group of xPVP was observed, resulting in slower release of the drug after fast disintegration. SLS was found to have a significant impact on the processability due to its lubricating effect, resulting in higher compression forces needed to achieve the target tablet hardness. Due to the higher degree of compression, the disintegration and dissolution of both drugs became slower despite the wetting effect of SLS.

First results from the US-PRC PMI collaboration on EAST

NASA Astrophysics Data System (ADS)

Maingi, R.; Lunsford, R.; Mansfield, D.; Diallo, A.; Hu, J.; Sun, Z.; Zuo, G.; Gong, X.; Tritz, K.; Canik, J.; Osborne, T.; EAST Team

2017-10-01

A US-PRC collaboration was formed to understand the plasma-material interface for improved long pulse discharge performance in EAST, with an emphasis on Li conditioning techniques. The US multi-institutional team consists of participants from PPPL, UI-UC, UT-K, ORNL, MIT, LANL, and JHU. In Dec. 2016, this team co-led experiments on the use of Li aerosol injection to mitigate ELMs, Li granule injection to pace ELMs, and a flowing liquid Li limiter to serve as a primary plasma-facing component. Li aerosol injection was shown to eliminate ELMs using the upper ITER-like W divertor, extending previous results of ELM suppression in the lower cabon divertor (J.S. Hu, PRL 2015). In addition Li granule injection was shown to trigger and even pace ELMs, although the paced ELM frequency was slower than the natural ELM frequency in this set of experiments; previously paced ELM frequency was comparable to natural ELMs frequency (D.K. Mansfield, NF 2013). Finally a second generation flowing liquid Li limiter was shown to be compatible with ELMy H-mode plasmas, pushed within 1 cm of the separatrix. The surface showed no damage to PMI and improved wetting as compared to the first generation limiter experiments (J.S. Hu, NF 2016 and G.Z. Zuo, NF 2017). US scientists supported in part by US DoE contracts DE-AC02-09CH11466, DE-FG02-09ER55012, DE-AC05-00OR22725, and DE-FC02-04ER54698, and ASIPP scientists by Contract No. 11625524, No. 11075185, No. 11021565, and No. 2013GB114004.

Multi-species impurity granule injection and mass deposition projections in NSTX-U discharges

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lunsford, R.; Bortolon, A.; Roquemore, A. L.

Here, by employing a neutral gas shielding (NGS) model to characterize impurity granule injection, the ablation rates for three different species of granule: lithium, boron, and carbon, are determined. Utilizing the duration of ablation events recorded on experiments performed at DIII-D to calibrate the NGS model, we quantify the ablation rate with respect to the plasma density profile. The species-specific granule shielding constant is then used to model granule ablation within NSTX-U discharges. Simulations of 300, 500 and 700 micron diameter granules injected at 50 m s –1 are presented for NSTX-U L-mode type plasmas, as well as H-mode dischargesmore » with low natural ELM frequency. Additionally, ablation calculations of 500 micron granules of each species are presented at velocities ranging from 50–150 m s –1. In H-mode discharges these simulations show that the majority of the injected granule is ablated within or just past the edge steep gradient region. At this radial position, the perturbation to the background plasma generated by the ablating granule can lead to conditions advantageous for the rapid triggering of ELM crashes.« less

Multi-species impurity granule injection and mass deposition projections in NSTX-U discharges

DOE PAGES

Lunsford, R.; Bortolon, A.; Roquemore, A. L.; ...

2017-05-16

Here, by employing a neutral gas shielding (NGS) model to characterize impurity granule injection, the ablation rates for three different species of granule: lithium, boron, and carbon, are determined. Utilizing the duration of ablation events recorded on experiments performed at DIII-D to calibrate the NGS model, we quantify the ablation rate with respect to the plasma density profile. The species-specific granule shielding constant is then used to model granule ablation within NSTX-U discharges. Simulations of 300, 500 and 700 micron diameter granules injected at 50 m s –1 are presented for NSTX-U L-mode type plasmas, as well as H-mode dischargesmore » with low natural ELM frequency. Additionally, ablation calculations of 500 micron granules of each species are presented at velocities ranging from 50–150 m s –1. In H-mode discharges these simulations show that the majority of the injected granule is ablated within or just past the edge steep gradient region. At this radial position, the perturbation to the background plasma generated by the ablating granule can lead to conditions advantageous for the rapid triggering of ELM crashes.« less

PtdIns(4,5)P2 is not required for secretory granule docking.

PubMed

Omar-Hmeadi, Muhmmad; Gandasi, Nikhil R; Barg, Sebastian

2018-06-01

Phosphoinositides (PtdIns) play important roles in exocytosis and are thought to regulate secretory granule docking by co-clustering with the SNARE protein syntaxin to form a docking receptor in the plasma membrane. Here we tested this idea by high-resolution total internal reflection imaging of EGFP-labeled PtdIns markers or syntaxin-1 at secretory granule release sites in live insulin-secreting cells. In intact cells, PtdIns markers distributed evenly across the plasma membrane with no preference for granule docking sites. In contrast, syntaxin-1 was found clustered in the plasma membrane, mostly beneath docked granules. We also observed rapid accumulation of syntaxin-1 at sites where granules arrived to dock. Acute depletion of plasma membrane phosphatidylinositol (4,5) bisphosphate (PtdIns(4,5)P 2 ) by recruitment of a 5'-phosphatase strongly inhibited Ca 2+ -dependent exocytosis, but had no effect on docked granules or the distribution and clustering of syntaxin-1. Cell permeabilization by α-toxin or formaldehyde-fixation caused PtdIns marker to slowly cluster, in part near docked granules. In summary, our data indicate that PtdIns(4,5)P 2 accelerates granule priming, but challenge a role of PtdIns in secretory granule docking or clustering of syntaxin-1 at the release site. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Three novel proteins co-localise with polyhydroxybutyrate (PHB) granules in Rhodospirillum rubrum S1.

PubMed

Narancic, Tanja; Scollica, Elisa; Cagney, Gerard; O'Connor, Kevin E

2018-04-01

Polyhydroxybutyrate (PHB), a biodegradable polymer accumulated by bacteria is deposited intracellularly in the form of inclusion bodies often called granules. The granules are supramolecular complexes harbouring a varied number of proteins on their surface, which have specific but incompletely characterised functions. By comparison with other organisms that produce biodegradable polymers, only two phasins have been described to date for Rhodosprillum rubrum, raising the possibility that more await discovery. Using a comparative proteomics strategy to compare the granules of wild-type R. rubrum with a PHB-negative mutant housing artificial PHB granules, we identified four potential PHB granules' associated proteins. These were: Q2RSI4, an uncharacterised protein; Q2RWU9, annotated as an extracellular solute-binding protein; Q2RQL4, annotated as basic membrane lipoprotein; and Q2RQ51, annotated as glucose-6-phosphate isomerase. In silico analysis revealed that Q2RSI4 harbours a Phasin_2 family domain and shares low identity with a single-strand DNA-binding protein from Sphaerochaeta coccoides. Fluorescence microscopy found that three proteins Q2RSI4, Q2EWU9 and Q2RQL4 co-localised with PHB granules. This work adds three potential new granule associated proteins to the repertoire of factors involved in bacterial storage granule formation, and confirms that proteomics screens are an effective strategy for discovery of novel granule associated proteins.

Deubiquitylases USP5 and USP13 are recruited to and regulate heat-induced stress granules through their deubiquitylating activities.

PubMed

Xie, Xuan; Matsumoto, Shunsuke; Endo, Akinori; Fukushima, Toshiaki; Kawahara, Hiroyuki; Saeki, Yasushi; Komada, Masayuki

2018-04-12

Stress granules are transient cytoplasmic foci induced by various stresses that contain translation-stalled mRNAs and RNA-binding proteins. They are proposed to modulate mRNA translation and stress responses. Here, we show that the deubiquitylases USP5 and USP13 are recruited to heat-induced stress granules. Heat-induced stress granules also contained K48- and K63-linked ubiquitin chains. Depletion of USP5 or USP13 resulted in elevated ubiquitin chain levels and accelerated assembly of heat-induced stress granules, suggesting that these enzymes regulate the stability of the stress granules through their ubiquitin isopeptidase activity. Moreover, disassembly of heat-induced stress granules after returning the cells to normal temperatures was markedly repressed by individual depletion of USP5 or USP13. Finally, overexpression of a ubiquitin mutant lacking the C-terminal diglycine motif caused the accumulation of unanchored ubiquitin chains and the repression of the disassembly of heat-induced stress granules. As unanchored ubiquitin chains are preferred substrates for USP5, we suggest that USP5 regulates the assembly and disassembly of heat-induced stress granules by mediating the hydrolysis of unanchored ubiquitin chains while USP13 regulates stress granules through deubiquitylating protein-conjugated ubiquitin chains.This article has an associated First Person interview with the first author of the paper. © 2018. Published by The Company of Biologists Ltd.

Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.

PubMed

Currie, Erin; King, Brian; Lawrenson, Andrea L; Schroeder, Lena K; Kershner, Aaron M; Hermann, Greg J

2007-11-01

Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.

Strategies to suppress hydrogen-consuming microorganisms affect macro and micro scale structure and microbiology of granular sludge.

PubMed

Abreu, A A; Alves, J I; Pereira, M A; Sousa, D Z; Alves, M M

2011-08-01

Treatment of anaerobic granules with heat and two chemical treatments, contacting with 2-bromoethanesulfonate (BES) and with BES + Chloroform, were applied to suppress hydrogen-consuming microorganisms. Three mesophilic expanded granular sludge bed (EGSB) reactors-R(Heat), R(BES), and R(BES + Chlo)--were inoculated with the treated sludges and fed with synthetic sugar-based wastewater (5 g(COD) L(-1), HRT 20-12 h). Morphological integrity of granules and bacterial communities were assessed by quantitative image analysis and 16S rRNA gene based techniques, respectively. Hydrogen production in R(Heat) was under 300 mL H(2) L(-1) day(-1), with a transient peak of 1,000 mL H(2) L(-1) day(-1) after decreasing HRT. In R(BES + Chlo) hydrogen production rate did not exceed 300 mL H(2) L(-1) day(-1) and there was granule fragmentation, release of free filaments from aggregates, and decrease of granule density. In R(BES), there was an initial period with unstable hydrogen production, but a pulse of BES triggered its production rate to 700 ± 200 mL H(2) L(-1) day(-1). This strategy did not affect granules structure significantly. Bacteria branching within Clostridiaceae and Ruminococcaceae were present in this sludge. This work demonstrates that, methods applied to suppress H(2)-consuming microorganisms can cause changes in the macro- and microstructure of granular sludge, which can be incompatible with the operation of high-rate reactors. Copyright © 2011 Wiley Periodicals, Inc.

Angiogenic effect of platelet-rich plasma combined with gelatin hydrogel granules injected into murine subcutis.

PubMed

Kakudo, Natsuko; Morimoto, Naoki; Ogawa, Takeshi; Hihara, Masakatsu; Notodihardjo, Priscilla Valentin; Matsui, Makoto; Tabata, Yasuhiko; Kusumoto, Kenji

2017-07-01

Platelet-rich plasma (PRP), which contains highly concentrated platelets, is produced by centrifuging whole blood. It is a safe and readily available source of a wide range of growth factors necessary for angiogenesis. Gelatin hydrogel granules have been designed and prepared for the controlled release of many growth factors. The angiogenic effect of human PRP was examined in vitro, and the effect of its subcutaneous injection with gelatin hydrogel granules into murine subcutis was evaluated. Human PRP was prepared using a double-spin method. The concentration of growth factors and the platelet count were examined in PRP and in vitro, and the angiogenic activity of human umbilical vein endothelial cells (HUVECs) in co-culture with human dermal fibroblast cells (NHDFs) in the presence and absence of PRP was evaluated. Then, in vivo, PRP, either free or with gelatin hydrogel granules, was injected subcutaneously into tiebacks on mice. Using a microscope and Kurabo angiogenesis image analyser software, the area containing newly formed capillaries was evaluated histologically and the microvascular network score was calculated. PRP was shown to contain high concentrations of PDGF, VEGF and TGFβ and had an angiogenic effect on the co-culture system. PRP with gelatin hydrogel granules significantly enlarged the area containing newly formed capillaries and promoted the microvascular network in murine subcutaneous tissue. PRP encapsulated in gelatin hydrogel microspheres shows promise for enhancing angiogenic effects in murine subcutis and could represent a potential therapeutic combination for the treatment of ischaemic disorders. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Morphologic Integration of Hilar Ectopic Granule Cells into Dentate Gyrus Circuitry in the Pilocarpine Model of Temporal Lobe Epilepsy

PubMed Central

Cameron, Michael C.; Zhan, Ren-Zhi; Nadler, J. Victor

2014-01-01

After pilocarpine-induced status epilepticus, many granule cells born into the postseizure environment migrate aberrantly into the dentate hilus. Hilar ectopic granule cells (HEGCs) are hyperexcitable and may therefore increase circuit excitability. This study determined the distribution of their axons and dendrites. HEGCs and normotopic granule cells were filled with biocytin during whole-cell patch clamp recording in hippocampal slices from pilocarpine-treated rats. The apical dendrite of 86% of the biocytin-labeled HEGCs extended to the outer edge of the dentate molecular layer. The total length and branching of HEGC apical dendrites that penetrated the molecular layer were significantly reduced compared with apical dendrites of normotopic granule cells. HEGCs were much more likely to have a hilar basal dendrite than normotopic granule cells. They were about as likely as normotopic granule cells to project to CA3 pyramidal cells within the slice, but were much more likely to send at least one recurrent mossy fiber into the molecular layer. HEGCs with burst capability had less well-branched apical dendrites than nonbursting HEGCs, their dendrites were more likely to be confined to the hilus, and some exhibited dendritic features similar to those of immature granule cells. HEGCs thus have many paths along which to receive synchronized activity from normotopic granule cells and to transmit their own hyperactivity to both normotopic granule cells and CA3 pyramidal cells. They may therefore contribute to the highly interconnected granule cell hubs that have been proposed as crucial to development of a hyperexcitable, potentially seizure-prone circuit. PMID:21455997

Distorted secretory granule composition in mast cells with multiple protease deficiency.

PubMed

Grujic, Mirjana; Calounova, Gabriela; Eriksson, Inger; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Tchougounova, Elena; Kjellén, Lena; Pejler, Gunnar

2013-10-01

Mast cells are characterized by an abundance of secretory granules densely packed with inflammatory mediators such as bioactive amines, cytokines, serglycin proteoglycans with negatively charged glycosaminoglycan side chains of either heparin or chondroitin sulfate type, and large amounts of positively charged proteases. Despite the large biological impact of mast cell granules and their contents on various pathologies, the mechanisms that regulate granule composition are incompletely understood. In this study, we hypothesized that granule composition is dependent on a dynamic electrostatic interrelationship between different granule compounds. As a tool to evaluate this possibility, we generated mice in which mast cells are multideficient in a panel of positively charged proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast cells from these mice additionally lack mouse mast cell protease-5 protein. Mast cells from mice deficient in individual proteases showed normal morphology. In contrast, mast cells with combined protease deficiency displayed a profound distortion of granule integrity, as seen both by conventional morphological criteria and by transmission electron microscopy. An assessment of granule content revealed that the distorted granule integrity in multiprotease-deficient mast cells was associated with a profound reduction of highly negatively charged heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken together with previous findings showing that the storage of basic proteases conversely is regulated by anionic proteoglycans, these data suggest that secretory granule composition in mast cells is dependent on a dynamic interrelationship between granule compounds of opposite electrical charge.

Degradation of Glucan Primers in the Absence of Starch Synthase 4 Disrupts Starch Granule Initiation in Arabidopsis*

PubMed Central

Lu, Kuan-Jen; Stettler, Michaela; Streb, Sebastian

2016-01-01

Arabidopsis leaf chloroplasts typically contain five to seven semicrystalline starch granules. It is not understood how the synthesis of each granule is initiated or how starch granule number is determined within each chloroplast. An Arabidopsis mutant lacking the glucosyl-transferase, STARCH SYNTHASE 4 (SS4) is impaired in its ability to initiate starch granules; its chloroplasts rarely contain more than one large granule, and the plants have a pale appearance and reduced growth. Here we report that the chloroplastic α-amylase AMY3, a starch-degrading enzyme, interferes with granule initiation in the ss4 mutant background. The amy3 single mutant is similar in phenotype to the wild type under normal growth conditions, with comparable numbers of starch granules per chloroplast. Interestingly, the ss4 mutant displays a pleiotropic reduction in the activity of AMY3. Remarkably, complete abolition of AMY3 (in the amy3 ss4 double mutant) increases the number of starch granules produced in each chloroplast, suppresses the pale phenotype of ss4, and nearly restores normal growth. The amy3 mutation also restores starch synthesis in the ss3 ss4 double mutant, which lacks STARCH SYNTHASE 3 (SS3) in addition to SS4. The ss3 ss4 line is unable to initiate any starch granules and is thus starchless. We suggest that SS4 plays a key role in granule initiation, allowing it to proceed in a way that avoids premature degradation of primers by starch hydrolases, such as AMY3. PMID:27458017

Two Distinct Waxy Alleles Impact the Granule-Bound Starch Synthase in Sorghum

USDA-ARS?s Scientific Manuscript database

The granule-bound starch synthase (GBSS) is the enzyme responsible for amylose synthesis in starch granules. Loss of GBSS activity results in starch granules containing mostly amylopectin and little or no amylose, a phenotype described as waxy. Previously, two phenotypic classes of waxy alleles we...

NiaoDuQing granules relieve chronic kidney disease symptoms by decreasing renal fibrosis and anemia

PubMed Central

Wang, Xu; Yu, Suyun; Jia, Qi; Chen, Lichuan; Zhong, Jinqiu; Pan, Yanhong; Shen, Peiliang; Shen, Yin; Wang, Siliang; Wei, Zhonghong; Cao, Yuzhu; Lu, Yin

2017-01-01

NiaoDuQing (NDQ) granules, a traditional Chinese medicine, has been clinically used in China for over fourteen years to treat chronic kidney disease (CKD). To elucidate the mechanisms underlying the therapeutic benefits of NDQ, we designed an approach incorporating chemoinformatics, bioinformatics, network biology methods, and cellular and molecular biology experiments. A total of 182 active compounds were identified in NDQ granules, and 397 putative targets associated with different diseases were derived through ADME modelling and target prediction tools. Protein-protein interaction networks of CKD-related and putative NDQ targets were constructed, and 219 candidate targets were identified based on topological features. Pathway enrichment analysis showed that the candidate targets were mostly related to the TGF-β, the p38MAPK, and the erythropoietin (EPO) receptor signaling pathways, which are known contributors to renal fibrosis and/or renal anemia. A rat model of CKD was established to validate the drug-target mechanisms predicted by the systems pharmacology analysis. Experimental results confirmed that NDQ granules exerted therapeutic effects on CKD and its comorbidities, including renal anemia, mainly by modulating the TGF-β and EPO signaling pathways. Thus, the pharmacological actions of NDQ on CKD symptoms correlated well with in silico predictions. PMID:28915563

Selection of the best features for leukocytes classification in blood smear microscopic images

NASA Astrophysics Data System (ADS)

Sarrafzadeh, Omid; Rabbani, Hossein; Talebi, Ardeshir; Banaem, Hossein Usefi

2014-03-01

Automatic differential counting of leukocytes provides invaluable information to pathologist for diagnosis and treatment of many diseases. The main objective of this paper is to detect leukocytes from a blood smear microscopic image and classify them into their types: Neutrophil, Eosinophil, Basophil, Lymphocyte and Monocyte using features that pathologists consider to differentiate leukocytes. Features contain color, geometric and texture features. Colors of nucleus and cytoplasm vary among the leukocytes. Lymphocytes have single, large, round or oval and Monocytes have singular convoluted shape nucleus. Nucleus of Eosinophils is divided into 2 segments and nucleus of Neutrophils into 2 to 5 segments. Lymphocytes often have no granules, Monocytes have tiny granules, Neutrophils have fine granules and Eosinophils have large granules in cytoplasm. Six color features is extracted from both nucleus and cytoplasm, 6 geometric features only from nucleus and 6 statistical features and 7 moment invariants features only from cytoplasm of leukocytes. These features are fed to support vector machine (SVM) classifiers with one to one architecture. The results obtained by applying the proposed method on blood smear microscopic image of 10 patients including 149 white blood cells (WBCs) indicate that correct rate for all classifiers are above 93% which is in a higher level in comparison with previous literatures.

Effects of Two Chinese Herbal Formulae for the Treatment of Moderate to Severe Stable Chronic Obstructive Pulmonary Disease: A Multicenter, Double-Blind, Randomized Controlled Trial

PubMed Central

Cao, Yuxue; Du, Yijie; Zhang, Hongying; Luo, Qingli; Li, Bei; Wu, Jinfeng; Lv, Yubao; Sun, Jing; Jin, Hualiang; Wei, Kai; Zhao, Zhengxiao; Kong, Lingwen; Zhou, Xianmei; Miao, Qing; Wang, Gang; Zhou, Qingwei; Dong, Jingcheng

2014-01-01

Objective The study aims to evaluate the efficacy and safety of two Chinese herbal formulae for the treatment of stable COPD. Methods A multicenter, double-blind, double-dummy, and randomized controlled trial (RCT) was conducted. All groups were treated with additional conventional medicines. There were a 6-month treatment and a 12-month follow-up for 5 times. Primary outcomes included lung function test, exacerbation frequency, score of SGRQ. Second outcomes consisted of 6MWD, BODE index, psychological field score, inflammatory factors and cortisol. Results A total of 331 patients were randomly divided into two active treatment groups (Bushen Yiqi (BY) granule group, n = 109; Bushen Fangchuan (BF) tablet group, n = 109) and a placebo group (n = 113). Finally 262 patients completed the study. BY granule & BF tablet increased the values of VC, FEV1 (%) and FEV1/FVC (%), compared with placebo. BY granule improved PEF. Both treatments reduced acute exacerbation frequency (P = 0.067), BODE index and psychological field score, while improved 6MWD. In terms of descent rang of SGRQ score, both treatments increased (P = 0.01). Both treatments decreased inflammatory cytokines, such as IL-8, and IL-17(P = 0.0219). BY granule obviously descended IL-17(P<0.05), IL-1β (P = 0.05), IL-6, compared with placebo. They improved the level of IL-10 and cortisol. BY granule raised cortisol (P = 0.07) and decreased TNF-α. Both treatments slightly descended TGF-β1. In terms of safety, subject compliance and drug combination, there were no differences (P>0.05) among three groups. Conclusions BY granule and BF tablet were positively effective for the treatment of COPD, and the former performed better in general. Trial Registration Chinese Clinical Trial Register center ChiCTR-TRC-09000530 PMID:25118962

Protein Mobility within Secretory Granules

PubMed Central

Weiss, Annita Ngatchou; Bittner, Mary A.; Holz, Ronald W.; Axelrod, Daniel

2014-01-01

We investigated the basis for previous observations that fluorescent-labeled neuropeptide Y (NPY) is usually released within 200 ms after fusion, whereas labeled tissue plasminogen activator (tPA) is often discharged over many seconds. We found that tPA and NPY are endogenously expressed in small and different subpopulations of bovine chromaffin cells in culture. We measured the mobility of these proteins (tagged with fluorophore) within the lumen of individual secretory granules in living chromaffin cells, and related their mobilities to postfusion release kinetics. A method was developed that is not limited by standard optical resolution, in which a bright flash of strongly decaying evanescent field (∼64 nm exponential decay constant) produced by total internal reflection (TIR) selectively bleaches cerulean-labeled protein proximal to the glass coverslip within individual granules. Fluorescence recovery occurred as unbleached protein from distal regions within the 300 nm granule diffused into the bleached proximal regions. The fractional bleaching of tPA-cerulean (tPA-cer) was greater when subsequently probed with TIR excitation than with epifluorescence, indicating that tPA-cer mobility was low. The almost equal NPY-cer bleaching when probed with TIR and epifluorescence indicated that NPY-cer equilibrated within the 300 ms bleach pulse, and therefore had a greater mobility than tPA-cer. TIR-fluorescence recovery after photobleaching revealed a significant recovery of tPA-cer (but not NPY-cer) fluorescence within several hundred milliseconds after bleaching. Numerical simulations, which take into account bleach duration, granule diameter, and the limited number of fluorophores in a granule, are consistent with tPA-cer being 100% mobile, with a diffusion coefficient of 2 × 10−10 cm2/s (∼1/3000 of that for a protein of similar size in aqueous solution). However, the low diffusive mobility of tPA cannot alone explain its slow postfusion release. In the accompanying study, we suggest that, additionally, tPA itself stabilizes the fusion pore with dimensions that restrict its own exit. PMID:24988337

Wet Snow Mapping in Southern Ontario with Sentinel-1A Observations

NASA Astrophysics Data System (ADS)

Chen, H.; Kelly, R. E. J.

2017-12-01

Wet snow is defined as snow with liquid water present in an ice-water mix. It is can be an indicator for the onset of the snowmelt period. Knowledge about the extent of wet snow area can be of great importance for the monitoring of seasonal snowmelt runoff with climate-induced changes in snowmelt duration having implications for operational hydrological and ecological applications. Spaceborne microwave remote sensing has been used to observe seasonal snow under all-weather conditions. Active microwave observations of snow at C-band are sensitive to wet snow due to the high dielectric contrast with non-wet snow surfaces and synthetic aperture radar (SAR) is now openly available to identify and map the wet snow areas globally at relatively fine spatial resolutions ( 100m). In this study, a semi-automated workflow is developed from the change detection method of Nagler et al. (2016) using multi-temporal Sentinel-1A (S1A) dual-polarization observations of Southern Ontario. Weather station data and visible-infrared satellite observations are used to refine the wet snow area estimates. Wet snow information from National Operational Hydrologic Remote Sensing Center (NOHRSC) is used to compare with the S1A estimates. A time series of wet snow maps shows the variations in backscatter from wet snow on a pixel basis. Different land cover types in Southern Ontario are assessed with respect to their impacts on wet snow estimates. While forests and complex land surfaces can impact the ability to map wet snow, the approach taken is robust and illustrates the strong sensitivity of the approach to wet snow backscattering characteristics. The results indicate the feasibility of the change detection method on non-mountainous large areas and address the usefulness of Sentinel-1A data for wet snow mapping.

Probing the spatial dependence of the emission spectrum of single human retinal lipofuscin granules using near-field scanning optical microscopy.

PubMed

Haralampus-Grynaviski, N M; Lamb, L E; Simon, J D; Krogmeier, J R; Dunn, R C; Pawlak, A; Rózanowska, M; Sarna, T; Burke, J M

2001-08-01

The emission spectra of single lipofuscin granules are examined using spectrally resolved confocal microscopy and near-field scanning optical microscopy (NSOM). The emission spectrum varies among the granules examined revealing that individual granules are characterized by different distributions of fluorophores. The range of spectra observed is consistent with in vivo spectra of human retinal pigment epithelium cells. NSOM measurements reveal that the shape of the spectrum does not vary with position within the emissive regions of single lipofuscin granules. These results suggest that the relative distribution of fluorophores within the emissive regions of an individual granule is homogeneous on the spatial scale approximately 150 nm.