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Sample records for monohydrate granules formulated

  1. Granulation of increasingly hydrophobic formulations using a twin screw granulator.

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    Yu, Shen; Reynolds, Gavin K; Huang, Zhenyu; de Matas, Marcel; Salman, Agba D

    2014-11-20

    The application of twin screw granulation in the pharmaceutical industry has generated increasing interest due to its suitability for continuous processing. However, an understanding of the impact of formulation properties such as hydrophobicity on intermediate and finished product quality has not yet been established. Hence, the current work investigated the granulation behaviour of three formulations containing increasing amounts of hydrophobic components using a Consigma™-1 twin screw granulator. Process conditions including powder feed rate, liquid to solid ratio, granulation liquid composition and screw configuration were also evaluated. The size of the wet granules was measured in order to enable exploration of granulation behaviour in isolation without confounding effects from downstream processes such as drying. The experimental observations indicated that the granulation process was not sensitive to the powder feed rate. The hydrophobicity led to heterogeneous liquid distribution and hence a relatively large proportion of un-wetted particles. Increasing numbers of kneading elements led to high shear and prolonged residence time, which acted to enhance the distribution of liquid and feeding materials. The bimodal size distributions considered to be characteristic of twin screw granulation were primarily ascribed to the breakage of relatively large granules by the kneading elements.

  2. Hot-melt granulation in a twin screw extruder: effects of processing on formulations with caffeine and Ibuprofen.

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    Weatherley, Sharleen; Mu, Bo; Thompson, Michael R; Sheskey, Paul J; O'Donnell, Kevin P

    2013-12-01

    Hot-melt granulation (HMG) by twin screw extrusion is a novel technology for the continuous processing of pharmaceuticals but confidence must still be gained regarding whether the environment affects drug properties. In this preliminary study, granulation was studied for a model product containing lactose monohydrate and active ingredients of differing water solubility, namely ibuprofen versus caffeine. The formulations were granulated at 220 rpm and 100°C with polyethylene glycol binders of differing molecular weights and at concentrations between 6.5% and 20%. In terms of granule properties, the low melting point of ibuprofen had a dominant influence by producing larger, stronger granules, whereas the caffeine products were more comparable to a blank containing no active ingredient. Drug degradation was study by differential scanning calorimetry, X-ray diffraction, and high-pressure liquid chromatography. The only detected change was the dehydration of lactose monohydrate for the caffeine and blank products, whereas the lubricating influence of the ibuprofen protected its granules. The short residence time (∼60 s) was consider to be influential in minimizing damage of the drug despite the high temperature and shear attributed to HMG inside a twin screw extruder.

  3. Continuous melt granulation: Influence of process and formulation parameters upon granule and tablet properties.

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    Monteyne, Tinne; Vancoillie, Jochem; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

    2016-10-01

    The pharmaceutical industry has a growing interest in alternative manufacturing models allowing automation and continuous production in order to improve process efficiency and reduce costs. Implementing a switch from batch to continuous processing requires fundamental process understanding and the implementation of quality-by-design (QbD) principles. The aim of this study was to examine the relationship between formulation-parameters (type binder, binder concentration, drug-binder miscibility), process-parameters (screw speed, powder feed rate and granulation temperature), granule properties (size, size distribution, shape, friability, true density, flowability) and tablet properties (tensile strength, friability, dissolution rate) of four different drug-binder formulations using Design of experiments (DOE). Two binders (polyethylene glycol (PEG) and Soluplus®) with a different solid state, semi-crystalline vs amorphous respectively, were combined with two model-drugs, metoprolol tartrate (MPT) and caffeine anhydrous (CAF), both having a contrasting miscibility with the binders. This research revealed that the granule properties of miscible drug-binder systems depended on the powder feed rate and barrel filling degree of the granulator whereas the granule properties of immiscible systems were mainly influenced by binder concentration. Using an amorphous binder, the tablet tensile strength depended on the granule size. In contrast, granule friability was more important for tablet quality using a brittle binder. However, this was not the case for caffeine-containing blends, since these phenomena were dominated by the enhanced compression properties of caffeine Form I, which was formed during granulation. Hence, it is important to gain knowledge about formulation behavior during processing since this influences the effect of process parameters onto the granule and tablet properties.

  4. Evaluation of granulated lactose as a carrier for DPI formulations 1: effect of granule size.

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    Du, Ping; Du, Ju; Smyth, Hugh D C

    2014-12-01

    The objective of this study was to investigate the effect of large granulated lactose carrier particle systems on aerosol performance of dry powder inhaler formulations. Granulated lactose carriers with average sizes ranging from 200 to 1,000 μm were prepared and subsequently fractionated into separate narrow size powders. The fractionated granulated lactose (GL) samples were characterized in terms of size, specific surface area, surface roughness, morphology, density, flowability, and solid-state. The in vitro aerosolization performance was performed on the different size fractions of GL samples from a commercial inhaler device (Aerolizer®) with a model formulation (2% w/w salbutamol sulfate). The cascade impaction parameters employed were 60 or 90 L/min with standard (aperture size, 0.6 mm) or modified piercing holes (aperture size, 1.2 mm) of the inhaler loaded capsules. It was shown that the largest size fraction formulation (850-1000 μm) had a slight improvement in the fine particle fraction (FPF) compared to immediately preceding size fractions, explained by a smaller adhesive force between drug and carrier. Compared to commercial piercing holes, enlarged piercing holes generated a slight decreasing trend of FPF as the lactose powder sizes increased from 200-250 μm to 600-850 μm, perhaps due to the reduced detachment force by flow forces. The size, surface roughness, density, and flowability of lactose carrier as well as device design all contributed to the aerosol dispersion performance of granulated lactose-based adhesive mixtures. It was concluded that poorer or enhanced redispersion performance is not an inherent property to the significantly large size of granulated lactose carriers as previously contended.

  5. FORMULATION AND EVALUATION OF TASTE MASKED ORALLY DISINTEGRATING TABLETS OF SITAGLIPTIN PHOSPHATE MONOHYDRATE

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    Abbaraju Prasanna Lakshmi

    2012-09-01

    Full Text Available The purpose of the work is to mask the unpleasant taste of sitagliptin phosphate monohydrate with mannitol by co-grinding method and to formulate it as an oral disintegrating tablet by direct compression method. Drug-mannitol complexes were taken in 1:1, 1:1.5 and 1:2 ratios and tested for in vitro and in vivo bitter masking capacity of mannitol, drug content and molecular property. Different super-disintegrants like croscaramellose, sodium starch glycolate and crospovidone was used as disintegrating agents. The prepared tablets were characterized for tensile strength, wetting time, water absorption ratio, and In vitro and in vivo disintegration time. In addition, aspartame is used as sweetening agent which gives more pleasant taste in the mouth. Among all the formulations F1 to F6, Formulation F6 has good taste masking capacity and fast disintegration within 40sec. Furthermore, 96.7% of the drug has been released in 15min.The results disclosed that the productivity of taste masking of the drug has been done effectively with mannitol and 40mg of crosscarmellose sodium is efficient for rapid disintegrating of tablet.

  6. Scientific Opinion on safety and efficacy of coated granulated cobaltous carbonate monohydrate as feed additive for all species

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    EFSA Panel on Additives and Products or Substances used in Animal Feed

    2012-07-01

    Full Text Available

    Cobalt(III is a component of cobalamin. Its essentiality as trace element results from the capacity of certain animal species to synthesise cobalamin by the gastrointestinal microbiota. Feeding cobalt(II carbonate hydroxide (2:3 monohydrate up to the maximum authorised total cobalt in feed is safe for the target animals. Cobalt is predominantly excreted via the faecal route. Absorbed cobalt follows aqueous excretion routes. About 43 % of body cobalt is stored in muscle; however, kidney and liver are the edible tissues containing the highest cobalt concentrations and are most susceptible to reflect dietary cobalt concentrations. In animals with the capacity to synthesise cobalamin, cobalt is also deposited in tissues as vitamin B12. Cobalt(II cations are genotoxic under in vitro and in vivo conditions. Cobalt(II carbonate has carcinogen, mutagen and reproduction toxicant (CMR properties. No data are available on the potential carcinogenicity of cobalt(II following oral exposure. However, oral exposure may potentially entail adverse threshold-related effects in humans. The estimated population intake of cobalt most likely includes the contribution of foodstuffs from animals fed cobalt-supplemented feedingstuffs. An increase in cobalt exposure by the use of cobalt-containing feed additives is therefore not expected. Considering the population exposure to cobalt, about 4–10 times lower than the health-based guidance value, no safety concern for the consumer is expected for threshold effects of oral cobalt. Cobalt(II carbonate is a skin and eye irritant, and a dermal and respiratory sensitiser. Its dust is a hazard to persons handling the substance. Exposure by inhalation must be avoided. The use of cobalt from any source at the authorised maximum content in feed does not provide a risk to the environment. The coated granulated cobalt(II carbonate hydroxide (2:3 monohydrate is available for cobalamin synthesis in

  7. Continuous twin screw granulation of controlled release formulations with various HPMC grades.

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    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.

  8. Twin screw wet granulation: Effect of process and formulation variables on powder caking during production.

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    Saleh, Mohammed F; Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2015-12-30

    This work focuses on monitoring the behaviour and the mass of the built up/caking of powder during wet granulation using Twin Screw Granulator (TSG). The variables changed during this work are; powder (α-lactose monohydrate and microcrystalline cellulose (MCC)), the screw configuration (conveying and kneading elements) and the weight percentage of hydroxypropyl-methyl cellulose (HPMC) dissolved in the granulation liquid (i.e. changing liquid viscosity). Additionally, the effect of these variables on the size distribution, of the granules produced, was determined. The experiments were conducted using an acrylic transparent barrel. A stainless steel barrel was then used to conduct the two extreme granulation liquid viscosities with two different screw configurations, using lactose only. This was done to compare the findings to those obtained from the transparent barrel for validation purpose. These variables showed to affect the behaviour and the mass of the powder caking as well as the size distribution of granules. Overall, the use of kneading element resulted in uniform behaviour in caking with higher mass. Furthermore, increasing the amount of HPMC resulted in a reduction of the mass of powder caking for lactose, while showing inconsistent trend for MCC. Furthermore, lactose showed to have a greater tendency to cake in comparison to MCC. The results, for lactose, obtained from the stainless steel barrel compared well with their corresponding conditions from the transparent barrel, as the screw configuration and HPMC mass varied.

  9. Flow of formulation granules through a conical hopper

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    Mazumder B

    2008-01-01

    Full Text Available Gravity flow characteristics of various pharmaceutical granules through static conical hoppers of different cone angles were studied. Mass flow rate depends on properties of granules and cone angles when environmental conditions such as temperature and relative humidity are kept within a fixed range. The granules were made with active pharmaceutical ingredients as per Indian pharmacopoeia with other additives like binders and diluents. Lubricants were added with the granules to observe their effects on mass flow rate. Magnesium stearate and colloidal silicon dioxide of different proportions were used as lubricants after granulation. A new dimensionally analyzed equation was developed to predict flow rate of the granules. The developed equation agreed well with the experimental data with a percentage deviation of ±10%.

  10. Development of a controlled release formulation by continuous twin screw granulation: Influence of process and formulation parameters.

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    Vanhoorne, V; Vanbillemont, B; Vercruysse, J; De Leersnyder, F; Gomes, P; Beer, T De; Remon, J P; Vervaet, C

    2016-05-30

    The aim of this study was to evaluate the potential of twin screw granulation for the continuous production of controlled release formulations with hydroxypropylmethylcellulose as hydrophilic matrix former. Metoprolol tartrate was included in the formulation as very water soluble model drug. A premix of metoprolol tartrate, hydroxypropylmethylcellulose and filler (ratio 20/20/60, w/w) was granulated with demineralized water via twin screw granulation. After oven drying and milling, tablets were produced on a rotary Modul™ P tablet press. A D-optimal design (29 experiments) was used to assess the influence of process (screw speed, throughput, barrel temperature and screw design) and formulation parameters (starch content of the filler) on the process (torque), granule (size distribution, shape, friability, density) and tablet (hardness, friability and dissolution) critical quality attributes. The torque was dominated by the number of kneading elements and throughput, whereas screw speed and filling degree only showed a minor influence on torque. Addition of screw mixing elements after a block of kneading elements improved the yield of the process before milling as it resulted in less oversized granules and also after milling as less fines were present. Temperature was also an important parameter to optimize as a higher temperature yielded less fines and positively influenced the aspect ratio. The shape of hydroxypropylmethylcellulose granules was comparable to that of immediate release formulations. Tensile strength and friability of tablets were not dependent on the process parameters. The use of starch as filler was not beneficial with regard to granule and tablet properties. Complete drug release was obtained after 16-20h and was independent of the design's parameters.

  11. Developing wax-based granule formulations for mating disruption of oriental beetles (Coleoptera: Scarabaeidae) in turfgrass.

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    Behle, R W; Cossé, A A; Dunlap, C; Fisher, J; Koppenhöfer, A M

    2008-12-01

    Oriental beetle, Anomala orientalis Waterhouse (Coleoptera: Scarabaeidae), is a pest of turfgrass that may be controlled by applications of synthetic pheromone (Z)-/ (E)-7-tetradecen-2-one to disrupt mating. Laboratory experiments were conducted to determine release profiles of pheromone from experimental wax-based granules, a proprietary wax granule, and rubber septa commonly used in pheromone traps. Rubber septa loaded with 10, 100, and 300 microg per septum provided steady rates of pheromone release (zero-order) over 4 wk of laboratory evaluation (total = 1.1, 9.0, and 26.9 microg/4 wk, respectively). Septa with 1,000 microg per septum had a significant decline in the rate of pheromone release for this 4-wk exposure time (total = 119 microg/4 wk). A large proprietary wax granule (44 mg per granule, 25% wt:wt pheromone) provided a steady rate of pheromone release (total = 2,347 microg/4 wk per granule). Experimental granules (16 mg per granule) made of soywax with higher pheromone loads (10% wt:wt) approached zero-order release (steady state) (total = 69 microg/4 wk per granule), whereas smaller granules (4 mg per granule) with less pheromone (0.1% wt:wt) provided first-order release profiles (decreasing rate with longer exposure time) (total = 0.35 microg/4 wk per granule). A field trial in turfgrass demonstrated the potential of selected granular formulations to provide effective mating disruption for up to 4 wk, as measured by pheromone trap shutdown. Documenting pheromone release profiles for these experimental granules and rubber septa provides valuable information that will support future field evaluations of mating disruption as a control strategy.

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

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    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.

  13. Development and Evaluation of Taste Masked Granular Formulation of Satranidazole by Melt Granulation Technique

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    Harshal Ashok Pawar

    2014-01-01

    Full Text Available Drugs from nitroimidazole category are generally bitter in taste. Oral formulation with bitter taste is not palatable. Geriatrics and pediatrics patients usually suffer from swallowing difficulties. Many other patients in some disease conditions avoid swallowing tablets. Satranidazole is a new nitro-imidazole derivative with bitter taste and is available in market as film coated tablet. The purpose of this research was to mask the bitter taste of Satranidazole by coating complexation with low melting point wax and Eudragit EPO. Different types of wax (glyceryl monostearate, stearic acid and cetyl alcohol were tried for taste masking. The drug to stearic acid ratio 1 : 2 was found to be optimum on the basis of taste evaluation and in vitro release. The formulated granules were found to possess good flow property. FTIR studies confirmed that there was no interaction between drug and excipients. Scanning Electron Microscopy of drug and the optimized batch of granules was performed. The in vitro release of drug from granules was compared with marketed tablet formulation. The taste masked granules of optimized batch showed 87.65% release of drug in 1 hr which is comparable to that of marketed tablet formulation.

  14. Application of a convenient and cost-effective granulation technology for the formulation of tablets using conventional excipients

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    Nidhi Prakash Sapkal

    2014-01-01

    Full Text Available In the present investigation, suitability of a cost-effective and convenient granulation technique that is, moisture activated dry granulation (MADG process for high drug loading in tablet formulation was studied. In this work, effect of the amount of water on flow properties of granules as well as an effect of mixing time on surface morphology of granules was studied. Paracetamol (PCM immediate release granules were prepared using conventional excipients such as polyvinylpyrrolidone K-30, Kollidon VA 64 (as binders, and simple equipments by MADG technique. The prepared granules were evaluated for flow properties and tablets were compressed using optimized granule formulation. The prepared granules possessed good flow properties that is, angle of repose was 32.11 and percent compressibility index was 19.44. Tablets disintegrated in 2.08 min and 89% of the drug was released within 30 min. All the results were comparable with PCM tablets prepared by wet granulation method. Therefore, from the above studies it was concluded that MADG process may be effectively adopted by using Kollidon VA 64 as a binder in tablet formulations where high drug loading is to be achieved, where all the parameters of the formulation can be obtained within specified limits using this simple, convenient, less time consuming, economical, and efficient method of granulation.

  15. FORMULATION AND EVALUATION OF SUSTAINED RELEASE TABLET OF DILTIAZEM HYDROCHLORIDE BY MELT GRANULATION TECHNOLOGY

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    Birajdar Ganesh

    2013-07-01

    Full Text Available The objective behind present study was to formulate and evaluate sustained release tablet of Diltiazem hydrochloride by using different polymers by melt granulation technology and to study the effect of various concentrations of polymers on release rate from tablet. Tablets were prepared using bees wax, carnauba wax, paraffin wax as release ratardent polymers. The drug and excipient compatibility study was done by FTIR method using KBr pellet method. The granules prepared by melt granulation technique evaluated for characterization such as bulk density, tapped density, hausners ratio, angle of repose, cars index all granules shows good flow property. The tablet of Diltiazem HCL evaluated for characterization such as hardness, friability, weight variation and content uniformity all tablets shows sufficient hardness and friability shows that tablets are having sufficient strength. All results were satisfactory. The in vitro drug release studies for the prepared formulation were conducted for a period of 12 h using an EDT 08LX dissolution tester USP Type - II apparatus (rotating paddle set at 100 rpm and a temperature of 37 ± 0.5°C formulation was placed in the 900 ml of the medium. For first 2 h tablet was placed in 1.2 pH acidic medium which was replaced with 7.4 pH phosphate buffer for remaining 10 h. From the dissolution study and comparative graph it was concluded that increase in concentration of wax shows decrease in drug release from tablet. Batch F3 shows 99.84 % drug release at 12 h. In vitro release data of optimized formulations (Batch F3 was fitted to various kinetic models like zero order, first order, Higuchi, korsmeyer-peppas and pass Higuchi model as it has highest r2 value (0.955 among all models.

  16. Use of a continuous twin screw granulation and drying system during formulation development and process optimization.

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

    2015-01-01

    Since small scale is key for successful introduction of continuous techniques in the pharmaceutical industry to allow its use during formulation development and process optimization, it is essential to determine whether the product quality is similar when small quantities of materials are processed compared to the continuous processing of larger quantities. Therefore, the aim of this study was to investigate whether material processed in a single cell of the six-segmented fluid bed dryer of the ConsiGma™-25 system (a continuous twin screw granulation and drying system introduced by GEA Pharma Systems, Collette™, Wommelgem, Belgium) is predictive of granule and tablet quality during full-scale manufacturing when all drying cells are filled. Furthermore, the performance of the ConsiGma™-1 system (a mobile laboratory unit) was evaluated and compared to the ConsiGma™-25 system. A premix of two active ingredients, powdered cellulose, maize starch, pregelatinized starch and sodium starch glycolate was granulated with distilled water. After drying and milling (1000 μm, 800 rpm), granules were blended with magnesium stearate and compressed using a Modul™ P tablet press (tablet weight: 430 mg, main compression force: 12 kN). Single cell experiments using the ConsiGma™-25 system and ConsiGma™-1 system were performed in triplicate. Additionally, a 1h continuous run using the ConsiGma™-25 system was executed. Process outcomes (torque, barrel wall temperature, product temperature during drying) and granule (residual moisture content, particle size distribution, bulk and tapped density, hausner ratio, friability) as well as tablet (hardness, friability, disintegration time and dissolution) quality attributes were evaluated. By performing a 1h continuous run, it was detected that a stabilization period was needed for torque and barrel wall temperature due to initial layering of the screws and the screw chamber walls with material. Consequently, slightly deviating

  17. Formulation and evaluation of bilayer tablet by using melt granulation technique for treatment of diabetes mellitus.

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    Patel, Dhruvita; Patel, Ankita; Solanki, Trupti

    2012-03-01

    The objective of present study was to prepare and characterize Bilayer tablet formulation containing Metformin HCl in extended release matrix form and Pioglitazone HCl in immediate release form for the treatment of diabetes mellitus. Different formulations containing Metformin HCl were manufactured using 3(2) factorial designs. Influence of hydrophilic carrier, hydrophobic polymer on drug release was studied. Immediate release layer of Pioglitazone was optimized using different super disintegrants. All formulations were evaluated for percentage drug release. Optimization results indicated that release rate of Metformin is directly proportional to the levels of Eudragit S 100 and PEG 6000. Results confirmed that Bilayer tablet formulation containing extended release of Metformin HCl and immediate release of Pioglitazone HCl could be developed by using melt granulation technique.

  18. Influence of different formulations and granulation techniques on dissolution of folic acid in film coated tablets

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    Ljiljana Krsteska

    2011-07-01

    Full Text Available The vitamin folic acid has received considerable attention because of it′s role in decreasing risk of neural tube birth defects, and it′s potential role in reducing risks of cardiovascular and psychiatric diseases. We evaluated compositions of 5 different formulations in terms of meeting the USP standard for dissolution and disintegration .However all the examined formulations had met the disintegration test but only 3 formulations had met the dissolution requirements to release 75 % of the active ingredient in 45 minutes. The maximum value of dissolution of 97.52 % in S5 composition was achieved by combination of certain excipients (combination of hydrophilic and hydrophobic filler and suitable wetting agent and wet high shear mixing granulation technique, resulting with optimize release of the active substance.

  19. Prophylactic and therapeutic effects of a novel granulated formulation of Artemisia extract on broiler coccidiosis.

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    Kaboutari, Jahangir; Arab, Hossien Ali; Ebrahimi, Kambiz; Rahbari, Sadegh

    2014-01-01

    Coccidiosis is an important parasitic disease in poultry industry. Owing to the development of drug resistance against Eimeria and concerns about drug residues, attentions toward the alternative compounds including herbal medicines have been increased. This study aimed to examine the prophylactic and therapeutic effects of a new formulation derived from Artemisia sieberi extract on avian coccidiosis. The extract was obtained from A. sieberi using petroleum ether, and then, it was formulated into a wet granule. Three hundred and sixty 1-day-old broilers were divided into six groups, each with three replicates (n = 20); the first group was chosen as the noninfected control group and the remainders were challenged by oral administration of 250,000 oocysts of Eimeria tenella per chick on day 21. Group 2 (as nontreated control) received no treatment, but group 3 (as prophylactic group) received 0.5 mg/kg artemisinin 10 days before challenging with E. tenella. However, groups 4, 5, and 6 received 1 mg/kg artemisinin on the next day and at 24 and 48 h after the challenge, respectively, for 5 days. Mortality rate, bloody diarrhea score, lesion score, and oocysts per gram (OPG) of feces were used to determine the anticoccidial effects of the formulation. The granule significantly (p coccidiosis.

  20. An investigation of the influence of process and formulation variables on mechanical properties of high shear granules using design of experiment.

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    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.

  1. Formulation and evaluation of sustained release matrix tablet of rabeprazole using wet granulation technique

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    Ruqaiyah Khan

    2014-01-01

    Full Text Available Introduction: Rabeprazole, a member of substituted benzimidazoles, inhibits the final step in gastric acid secretions. This drug claims to cause fastest acid separation (due to higher pKa, and more rapidly converts to the active species to aid gastric mucin synthesis. The most significant pharmacological action of Rabeprazole is dose dependent suppression of gastric acid secretion; without anticholinergic or H2-blocking action. It completely abolishes the hydrochloric acid secretion as it is powerful inhibitor of gastric acid. Rabeprazole is acid labile and hence commonly formulated as an enteric coated tablet. The absorption of rabeprazole occurs rapidly as soon as tablet leaves the stomach. Aim: In the present study an attempt was made to formulate and evaluate Rabeprazole sustained release matrix tablet using wet granulation technique incorporating various polymers like HPMC-E15, Carbopol934, and sodium carboxymethyl cellulose (CMC. Materials and Methods: The Formulated tablets were evaluated for different physicochemical properties like rheological properties, weight variation, thickness, hardness, % friability, in vitro release studies and drug content. Results: Studies revealed that all the physicochemical parameters comply with the official standards. The in vitro release studies exhibits the release up to 90%, over a prolonged period of time which confirms the extended release profile of formulation, having better bioavailability as well as decreased dosing frequency with reduced doses. Conclusion: The sustained release matrix tablets of rabiprazole shown better bioavailability, efficacy and potency, when compared with official standards.

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

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    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.

  3. Bioequivalence of two formulations of montelukast sodium 4 mg oral granules in healthy adults.

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    Fey, Constanze; Thyroff-Friesinger, Ursula; Jones, Spencer

    2014-01-01

    Montelukast is an effective and well-tolerated treatment for the prophylaxis and chronic treatment of asthma, acute prevention of exercise-induced bronchoconstriction and symptomatic relief of seasonal allergic rhinitis and perennial allergic rhinitis. The aim of the study was to compare bioavailability, and characterise the pharmacokinetic profile and safety of Sandoz generic montelukast 4 mg oral granules relative to Singulair(®) mini (Merck, Sharp & Dohme). An open-label, randomised, single-dose, two-treatment, two-period, two-sequence, two-way crossover bioequivalence study was conducted in healthy male volunteers aged 18-55 years, under fasting conditions. The duration of the clinical part of the trial was ≈ 11 days. Montelukast levels in plasma were quantified using a validated liquid chromatography tandem mass spectrometry method, and pharmacokinetic parameters calculated from the drug concentration-time profile using a non-compartmental model. A total of 40 subjects completed both study periods. The ratio test/reference of geometric least squares means was calculated for both formulations of montelukast for the In-transformed pharmacokinetic parameters; the 90% confidence intervals (CIs) were within the pre-defined limits of 80.00-125.00%: 92.2% (90% CI: 87.42-97.30%) for Cmax, 98.1% (90% CI: 94.49-101.81%) for AUC0-t and 97.6% (90% CI: 94.14-101.27%) for AUC0-∞. Two study subjects each reported one mild adverse event: dyspepsia (possibly related to study medication) and throat pain (not considered related to study medication). Sandoz montelukast 4 mg oral granules are bioequivalent to Singulair(®) 4 mg mini oral granules, with a similar safety profile. This suggests that these two preparations can be considered interchangeable in clinical practice.

  4. Floating granules of ranitidine hydrochloride-gelucire 43/01: formulation optimization using factorial design.

    Science.gov (United States)

    Patel, Dasharath M; Patel, Natavarlal M; Patel, Viral F; Bhatt, Darshini A

    2007-04-13

    The purpose of this research was to develop and optimize a controlled-release multiunit floating system of a highly water soluble drug, ranitidine HCl, using Compritol, Gelucire 50/13, and Gelucire 43/01 as lipid carriers. Ranitidine HCl-lipid granules were prepared by the melt granulation technique and evaluated for in vitro floating and drug release. Ethyl cellulose, methylcellulose, and hydroxypropyl methylcellulose were evaluated as release rate modifiers. A 3(2) full factorial design was used for optimization by taking the amounts of Gelucire 43/01 (X (1)) and ethyl cellulose (X (2)) as independent variables, and the percentage drug released in 1(Q(1)), 5(Q(5)), and 10 (Q(10)) hours as dependent variables. The results revealed that the moderate amount of Gelucire 43/01 and ethyl cellulose provides desired release of ranitidine hydrochloride from a floating system. Batch F4 was considered optimum since it contained less Gelucire and was more similar to the theoretically predicted dissolution profile (f(2) = 62.43). The temperature sensitivity studies for the prepared formulations at 40 degrees C/75% relative humidity for 3 months showed no significant change in in vitro drug release pattern. These studies indicate that the hydrophobic lipid Gelucire 43/01 can be considered an effective carrier for design of a multiunit floating drug delivery system for highly water soluble drugs such as ranitidine HCl.

  5. Formulation of Granules for Site-Specific Delivery of an Antimicrobial Essential Oil to the Animal Intestinal Tract.

    Science.gov (United States)

    Ma, Yin-Hing; Wang, Qi; Gong, Joshua; Wu, Xiao Yu

    2016-03-01

    Owing to proliferation of antibiotic-resistant bacteria, the use of antibiotics for livestock growth promotion is banned in many countries and alternatives to in-feed antibiotics are needed. Cinnamon essential oil exhibits strong in vitro antibacterial activity; however, direct addition of essential oils to animal feed has limited practicality due to their high volatility, odor, fast decomposition, and poor availability in the lower intestines. To solve these problems, we formulated trans-cinnamaldehyde (CIN) with an adsorbent powder and fatty acid via a melt-solidification technique. Core granules of an optimized composition contained up to 48% wt/wt CIN. The granules were then coated with an enteric polymer to impart site-specific release of CIN. CIN was mostly retained in simulated gastric fluid and released rapidly (>80% under 2 h) in simulated intestinal fluids. Rapid CIN autoxidation into cinnamic acid was inhibited by adding 1% vol/vol eugenol, which maintained CIN stability for at least 1 y. The granule formulation increased the antimicrobial activity of CIN against Escherichia coli K88 slightly with a minimum bactericidal concentration of 450 μg/mL for CIN in lauric acid-based granules compared with 550-600 μg/mL for palmitic acid-based granules and free CIN, respectively. These results encourage the potential use of encapsulated CIN for control of animal enteric pathogens by oral in-feed administration.

  6. Novel in situ self-assembly nanoparticles for formulating a poorly water-soluble drug in oral solid granules, improving stability, palatability, and bioavailability

    Directory of Open Access Journals (Sweden)

    Guo S

    2016-04-01

    Full Text Available Shujie Guo,1 Kevin Pham,2 Diana Li,2 Scott R Penzak,3 Xiaowei Dong2 1State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pharmaceutical Sciences, 3Department of Pharmacotherapy, University of North Texas Health Science Center, Fort Worth, TX, USA Purpose: The purpose of this study was to develop a novel lipid-based nanotechnology to formulate poorly water-soluble drugs in oral solid granules to improve stability, palatability, and bioavailability. Materials and methods: In one method, we prepared ritonavir (RTV nanoparticles (NPs by a microemulsion-precursor method and then converted the RTV NPs to solid granules by wet granulation to produce RTV NP-containing granules. In the other innovative method, we did not use water in the formulation preparation, and discovered novel in situ self-assembly nanoparticles (ISNPs. We prepared RTV ISNP granules that did not initially contain NPs, but spontaneously produced RTV ISNPs when the granules were introduced to water with gentle agitation. We fully characterized these RTV nanoformulations. We also used rats to test the bioavailability of RTV ISNP granules. Finally, an Astree electronic tongue was used to assess the taste of the RTV ISNP granules. Results: RTV NP-containing granules only had about 1% drug loading of RTV in the solid granules. In contrast, RTV ISNP granules achieved over 16% drug loading and were stable at room temperature over 24 weeks. RTV ISNPs had particle size between 160 nm and 300 nm with narrow size distribution. RTV ISNPs were stable in simulated gastric fluid for 2 hours and in simulated intestinal fluid for another 6 hours. The data from the electronic tongue showed that the RTV ISNP granules were similar in taste to blank ISNP granules, but were much different from RTV solution. RTV ISNP granules increased RTV bioavailability

  7. Swietenolide monohydrate

    Directory of Open Access Journals (Sweden)

    Hasnah Osman

    2008-07-01

    Full Text Available The title compound, a natural b,d-seco-limonoid, C27H34O8·H2O, and known as Swietenolide monohydrate, has been isolated from S. macrophylla King. In the molecular structure, the four fused six-membered rings adopt twist-boat (ring A, approximate chair (ring B, envelope (ring C and half-chair (ring D conformations. The attached furan ring is essentially planar. O—H...O hydrogen bonds and weak C—H...O interactions connect the molecules into a two-dimensional network parallel to the (100 plane. C—H...π interactions are also observed.

  8. Defining the critical material attributes of lactose monohydrate in carrier based dry powder inhaler formulations using artificial neural networks.

    Science.gov (United States)

    Kinnunen, Hanne; Hebbink, Gerald; Peters, Harry; Shur, Jagdeep; Price, Robert

    2014-08-01

    The study aimed to establish a function-based relationship between the physical and bulk properties of pre-blended mixtures of fine and coarse lactose grades with the in vitro performance of an adhesive active pharmaceutical ingredient (API). Different grades of micronised and milled lactose (Lactohale (LH) LH300, LH230, LH210 and Sorbolac 400) were pre-blended with coarse grades of lactose (LH100, LH206 and Respitose SV010) at concentrations of 2.5, 5, 10 and 20 wt.%. The bulk and rheological properties and particle size distributions were characterised. The pre-blends were formulated with micronised budesonide and in vitro performance in a Cyclohaler device tested using a next-generation impactor (NGI) at 90 l/min. Correlations between the lactose properties and in vitro performance were established using linear regression and artificial neural network (ANN) analyses. The addition of milled and micronised lactose fines with the coarse lactose had a significant influence on physical and rheological properties of the bulk lactose. Formulations of the different pre-blends with budesonide directly influenced in vitro performance attributes including fine particle fraction, mass median aerodynamic diameter and pre-separator deposition. While linear regression suggested a number of physical and bulk properties may influence in vitro performance, ANN analysis suggested the critical parameters in describing in vitro deposition patterns were the relative concentrations of lactose fines % < 4.5 μm and % < 15 μm. These data suggest that, for an adhesive API, the proportion of fine particles below % < 4.5 μm and % < 15 μm could be used in rational dry powder inhaler formulation design.

  9. Optimization of metoprolol tartrate modified-release matrix tablet formulation using Eudragit NE as binder for metoprolol fluid bed granulation

    Directory of Open Access Journals (Sweden)

    Ioan Tomuta

    2012-01-01

    Full Text Available The aim of this experimental work was to investigate the possibility of obtaining hydroxypropyl methylcellulose (HPMC hydrophilic matrix extended-release dosage forms with metoprolol by using aqueous dispersions of Eudragit NE, as binders in fluid bed granulation. To evaluate the influence of formulation variables (levels of HPMC-Methocel K100 M and Surelease E7 19010 on drug release during a period of time of 12 hours, and on the kinetic release, a full factorial experimental design with two factors and three levels was used. The formulation factors were the granulation polymer concentration and the matrix-forming polymer concentration. The obtained results have shown that the percentage of the drug released during the 12 hours is influenced both by the Methocel ratio and the Eudragit NE ratio; increasing the ratios of Eudragit and Methocel leads to the decrease of the percentage of the released drug. The influence of Eudragit NE percentage is maximum at four and six hours, but the influence of Methocel K100 M concentration is almost the same at all sampling times; all studied formulations showed a kinetic release that fitted best with the Peppas model.

  10. Isovaline monohydrate

    Directory of Open Access Journals (Sweden)

    Jason P. Dworkin

    2013-12-01

    Full Text Available The title compound, C5H11NO2·H2O, is an isomer of the α-amino acid valine that crystallizes from water in its zwitterion form as a monohydrate. It is not one of the 20 proteinogenic amino acids that are used in living systems and differs from the natural amino acids in that it has no α-H atom. The compound exhibits hydrogen bonding between the water molecule and the carboxylate O atoms and an amine H atom. In addition, there are intermolecular hydrogen-bonding interactions between the carboxylate O atoms and amine H atoms. In the crystal, these extensive N—H...O and O—H...O hydrogen bonds lead to the formation of a three-dimensional network.

  11. High-shear granulation as a manufacturing method for cocrystal granules

    DEFF Research Database (Denmark)

    Rehder, Sönke; Christensen, Niels Peter Aae; Rantanen, Jukka

    2013-01-01

    influenced by the excipients, since in presence of calcium hydrogenphosphate, the poorly water-soluble salt calcium tartrate monohydrate was formed at high relative humidity. Interestingly, compactability was increased by cocrystal formation compared to that of the reference granules (piracetam...

  12. "Rolling" phenomenon in twin screw granulation with controlled-release excipients.

    Science.gov (United States)

    Thompson, M R; O'Donnell, K P

    2015-03-01

    The developed knowledge regarding use of twin screw granulators for continuous wet granulation has been primarily limited to immediate release formulations in the literature. The present study highlights an issue previously unreported for wet granulation with twin screw extruders when using formulations containing controlled-release (CR) excipients. Long (3-10 mm), twisted noodle-like granules can be produced in the presence of these excipients that are difficult to control and are anticipated to create complications in downstream unit operations to the granulator. Working with two different CR excipients, METHOCEL™ K4M and Kollidon® SR, each blended at different ratios with a mixture of 80% α-lactose monohydrate/20% microcrystalline cellulose, these unique particles were found to be produced in the conveying elements of the extruder, arising from a rolling action at the top of the screw flights. The CR excipients adhesively strengthen the wetted mass, forming this undesired granule shape such that they persisted to the exit of the machine; the shape appeared most strongly affected by screw speed, producing particles of higher aspect ratio as speed was increased. Adjusting the concentration of these CR excipients in the formulation, the flow rate or the type of compression element used in the screws proved ineffective in controlling the problem. Rather, a re-design of the extruder screws was required to prevent generation of these extended-form granules.

  13. Foam granulation: new developments in pharmaceutical solid oral dosage forms using twin screw extrusion machinery.

    Science.gov (United States)

    Thompson, M R; Weatherley, S; Pukadyil, R N; Sheskey, P J

    2012-07-01

    This paper investigates foam granulation in a twin screw extruder as a new continuous wet granulation technique for pharmaceutical powder drug formulations. Foamed aqueous binder has a reportedly lower soak-to-spread ratio than drop or spray liquid addition in batch granulation. This work demonstrates a twin screw extruder configuration for foam granulation and subsequently compares the new approach against liquid injection in the granulation of α-lactose monohydrate with a methylcellulose binder. Trials were conducted at high powder output rates (20-40 kg/h) and high screw speeds (220-320 RPM) with two screw configurations. Process stability improved with the new technique allowing granulation with less binder. The extruded mass maintained a low exit temperature, being insensitive to operating conditions unlike the liquid injection approach, where temperatures rose significantly as flow rate increased. The particle size distribution by foam granulation reflected a more uniformly wetted mass with larger granule growth noted even for conditions where dry powder exited by liquid injection. Other factors were found similar between the two binder delivery methods such as consumed mechanical energy, as well as fracture strength and compressibility of produced granules.

  14. The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG).

    Science.gov (United States)

    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.

  15. The importance of binder moisture content in Metformin HCL high-dose formulations prepared by moist aqueous granulation (MAG

    Directory of Open Access Journals (Sweden)

    Hiroshi Takasaki

    2015-01-01

    Full Text Available 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.

  16. Impact and attrition shear breakage of enzyme granules and placebo particles-application to particle design and formulation

    DEFF Research Database (Denmark)

    Jørgensen, Kåre; Bach, Poul; Jensen, Anker

    2005-01-01

    The strength and breakage mechanisms of detergent enzyme granules and typical core materials used for enzyme granules (all of size 500-600 mum) have been investigated under impact and shear stress conditions to simulate the stresses experienced in a detergent factory. In an Impact Tester, single...... breakage mechanism after repeated impacts at 10 m/s is chipping associated with local delamination. Damages to the coating layer may expose the underlying enzyme-containing layer or core and lead to the release of enzyme-active dust. Markedly lower enzyme dust release was obtained by incorporating...... the enzyme into the core of the granule as compared to a layer-structured enzyme distribution. Furthermore, the results indicated that stronger enzyme granule core materials provide a better impact resistance of the final enzyme granule towards the release of enzyme-active dust. Coating layers of inorganic...

  17. Influence of filler selection on twin screw foam granulation.

    Science.gov (United States)

    Rocca, K E; Weatherley, S; Sheskey, P J; Thompson, M R

    2015-01-01

    The influence of filler selection in wet granulation was studied for the novel case where the binder is delivered as an unstable, semi-rigid aqueous foam to an extrusion process. The work primarily examined the impact of differing concentrations of microcrystalline cellulose (Avicel PH® 101) in a formulation with spray-dried α-lactose monohydrate (Flowlac® 100) in regards to wetting and granule nucleation for this relatively new technique known as continuous foam granulation. Foam stability was varied within the work to change its drainage and coarsening behavior atop these powder excipients, by use of different foamable binding agents (METHOCEL™ F4 PLV and METHOCEL™ Premium VLV) as well as by adjusting the foam quality. A static bed penetration test was first used to study the foam behavior in wetting these powders without the processing constraints of an extruder which limit possible liquid-to-solids ratios as well as introduce shear which may complicate interpretation of the mechanism. The test found that the penetration time to saturate these powders decreased as their water absorption capacity increased which in turn decreased the size of the formed nuclei. Differences in the stability of the foamed binder had minimal influence on these attributes of wetting despite its high spread-to-soak behavior. The size of granules produced by extrusion similarly demonstrated sensitivity to the increasing water absorption capacity of the filler and little dependency on foam properties. The different liquid-to-solids ratios required to granulate these different formulations inside the extruder highlighted an evolving concept of powder lubricity for continuous foam granulation.

  18. Granulation by roller compaction and enteric coated tablet formulation of the extract of the seeds of Glinus lotoides loaded on Aeroperl 300 Pharma.

    Science.gov (United States)

    Endale, Abebe; Gebre-Mariam, Tsige; Schmidt, Peter C

    2008-01-01

    The purpose of this research was to improve the hygroscopicity and poor flow properties of the crude dry extract of the seeds of Glinus lotoides and improve the disintegration time of the core-tablets for enteric coated formulation thereof. The liquid crude extract of the plant was adsorbed on granulated colloidal silicon dioxide (Aeroperl 300 Pharma) at 30% w/w and the dry extract preparation (DEP) was dry-granulated with roller-compaction using Micro-Pactor. Hygroscopicity, flow property and disintegration time were improved significantly due to the adsorption and granulation processes. Moreover, the DEP does not become mucilaginous even at higher relative humidity levels (above 65%). Oblong tablets (20 x 8.25 mm) containing 947 mg of the granulated DEP (equivalent to the traditional dose), 363 mg of Avicel PH101 and 90 mg of Ac-di-Sol as disintegrant were formulated using an instrumented eccentric tablet machine at 20 kN. The tablets showed a crushing strength of 195 N, a friability of 0.4% and disintegrated within 9 min. The tablets were then enteric coated using polymethacrylate co-polymers (Eudragit L 100-55 and Kollicoat MAE 100P). The coated tablets resisted disintegration or softening in simulated gastric fluid for a minimum of 2 h and disintegrated within 15 min in intestine simulated fluid at pH 6.8. In addition to controlling the release of the active agents, the enteric coating improved the strength and decreased friability of the core-tablets.

  19. Formulation and the in-vitro and biopharmaceutical evaluation of sustained release tablet of verapamil HCL using precirol ATO 5 through melt granulation technique

    Directory of Open Access Journals (Sweden)

    Bhagwat Durgacharan

    2009-01-01

    Full Text Available Sustained release tablet of Verapamil hydrochloride (VPH was prepared by using Precirol ATO 5 (PREC by direct compression of matrices prepared by using the melt granulation technique. The effect of different concentrations of PREC on the in-vitro drug release of VPH was studied by comparing it with the marketed formulation and percent release given in USP for VPH extended release tablets. Effect of release enhancers such as microcrystalline cellulose (MCC and lactose on in-vitro drug release was also studied. Biopharmaceutical evaluation of the satisfactory formulation was also performed in order to estimate the maximum concentration of drug in plasma (C max , time required to reach maximum concentration (t max , elimination rate constant (k, elimination rate constant (t 1/2 , area under curve (AUC (0-t and AUC (02a, apparent volume of distribution (V d and mean residence time. The results showed that PREC can be utilized as the matrix forming agent to sustain the release of VPH. The results of biopharmaceutical evaluation showed that the rate of absorption appeared to be more sustained, resulting in a more uniform plasma concentration profile of VPH. More bioavailability was noted with the sustained release formulation even though the drug has substantial first pass metabolism. The results indicated that it is possible to make once-a-day sustained-release tablet of VPH by using the melt granulation technique.

  20. Formulation and development of pH-independent/dependent sustained release matrix tablets of ondansetron HCl by a continuous twin-screw melt granulation process.

    Science.gov (United States)

    Patil, Hemlata; Tiwari, Roshan V; Upadhye, Sampada B; Vladyka, Ronald S; Repka, Michael A

    2015-12-30

    The objective of the present study was to develop pH-independent/dependent sustained release (SR) tablets of ondansetron HCl dihydrate (OND), a selective 5-HT3 receptor antagonist that is used for prevention of nausea and vomiting caused by chemotherapy, radiotherapy and postoperative treatment. The challenge with the OND API is its pH-dependent solubility and relatively short elimination half-life. Therefore, investigations were made to solve these problems in the current study. Formulations were prepared using stearic acid as a binding agent via a melt granulation process in a twin-screw extruder. The micro-environmental pH of the tablet was manipulated by the addition of fumaric acid to enhance the solubility and release of OND from the tablet. The in vitro release study demonstrated sustained release for 24h with 90% of drug release in formulations using stearic acid in combination with ethyl cellulose, whereas 100% drug release in 8h for stearic acid-hydroxypropylcellulose matrices. The formulation release kinetics was correlated to the Higuchi diffusion model and a non-Fickian drug release mechanism. The results of the present study demonstrated for the first time the pH dependent release from hydrophilic-lipid matrices as well as pH independent release from hydrophobic-lipid matrices for OND SR tablets manufactured by means of a continuous melt granulation technique utilizing a twin-screw extruder.

  1. TABLETING PROPERTIES OF EXPERIMENTAL AND COMMERCIALLY AVAILABLE LACTOSE GRANULATIONS FOR DIRECT COMPRESSION

    NARCIS (Netherlands)

    BOLHUIS, GK; ZUURMAN, K

    1995-01-01

    Lactose granulations (125-250 mu m) were prepared from two different alpha-lactose monohydrate powders and one roller dried beta-lactose powder respectively, by wet granulation with only water as a binder. As an effect of the granulation process, the flow properties improved, but the compactibility

  2. Enteric coating of granules containing the probiotic Lactobacillus acidophilus

    Directory of Open Access Journals (Sweden)

    Pyar Hassan

    2014-06-01

    Full Text Available In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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.

  5. RNA granules

    OpenAIRE

    Anderson, Paul; Kedersha, Nancy

    2006-01-01

    Cytoplasmic RNA granules in germ cells (polar and germinal granules), somatic cells (stress granules and processing bodies), and neurons (neuronal granules) have emerged as important players in the posttranscriptional regulation of gene expression. RNA granules contain various ribosomal subunits, translation factors, decay enzymes, helicases, scaffold proteins, and RNA-binding proteins, and they control the localization, stability, and translation of their RNA cargo. We review the relationshi...

  6. 2-Methylaspartic acid monohydrate

    Directory of Open Access Journals (Sweden)

    Ray J. Butcher

    2013-12-01

    Full Text Available The title compound, C5H9NO4·H2O, is an isomer of the α-amino acid glutamic acid that crystallizes from water in its zwitterionic form as a monohydrate. It is not one of the 20 proteinogenic α-amino acids that are used in living systems and differs from the natural amino acids in that it has an α-methyl group rather than an α-H atom. In the crystal, an O—H...O hydrogen bond is present between the acid and water molecules while extensive N—H...O and O—H...O hydrogen bonds link the components into a three-dimensional array.

  7. Continuous twin screw granulation: influence of process variables on granule and tablet quality.

    Science.gov (United States)

    Vercruysse, J; Córdoba Díaz, D; Peeters, E; Fonteyne, M; Delaet, U; Van Assche, I; De Beer, T; Remon, J P; Vervaet, C

    2012-09-01

    The aim of the current study was to screen theophylline (125 mg) tablets manufactured via twin screw granulation in order to improve process understanding and knowledge of process variables that determine granule and tablet quality. A premix of theophylline anhydrate, α-lactose monohydrate and PVP (ratio: 30/67.5/2.5,w/w) was granulated with demineralized water. Experiments were done using the high-shear wet granulation module (based on twin screw granulation) of the ConsiGma™-25 unit (a continuous tablet manufacturing system) for particle size enlargement. After drying, granules were compressed using a MODUL™ P tablet press (compression force: 10 kN, tablet diameter: 12 mm). Using a D-optimal experimental design, the effect of several process variables (throughput (10-25 kg/h), screw speed (600-950 rpm), screw configuration (number (2, 4, 6 and 12) and angle (30°, 60° and 90°) of kneading elements), barrel temperature (25-40°C) and method of binder addition (dry versus wet)) on the granulation process (torque and temperature increase in barrel wall), granule (particle size distribution, friability and flowability) and tablet (tensile strength, porosity, friability, disintegration time and dissolution) quality was evaluated. The results showed that the quality of granules and tablets can be optimized by adjusting specific process variables (number of kneading elements, barrel temperature and binder addition method) during a granulation process using a continuous twin screw granulator.

  8. Bacterial Larvicide, Bacillus thuringiensis israelensis Strain AM 65-52 Water Dispersible Granule Formulation Impacts Both Dengue Vector, Aedes aegypti (L.) Population Density and Disease Transmission in Cambodia

    Science.gov (United States)

    Socheat, Doung

    2016-01-01

    A multi-phased study was conducted in Cambodia from 2005–2011 to measure the impact of larviciding with the bacterial larvicide, Bacillus thuringiensis israelensis (Bti), a water dispersible granule (WG) formulation on the vector, Aedes aegypti (L.) and the epidemiology. In our studies, all in-use containers were treated at 8 g/1000 L, including smaller containers and animal feeders which were found to contribute 23% of Ae aegypti pupae. The treated waters were subjected to routine water exchange activities. Pupal production was suppressed by an average 91% for 8 weeks. Pupal numbers continued to remain significantly lower than the untreated commune (UTC) for 13 weeks post treatment in the peak dengue vector season (p50% of the household in the UTC harbored ≥11 mosquitoes per home. The adult population continued to remain at significantly much lower numbers in the Bti treated commune than in the UTC for 10–12 weeks post treatment (p<0.05). In 2011, a pilot operational program was evaluated in Kandal Province, a temephos resistant site. It was concluded that 2 cycles of Bti treatment in the 6 months monsoon season with complete coverage of the target districts achieved an overall dengue case reduction of 48% in the 6 treated districts compared to the previous year, 2010. Five untreated districts in the same province had an overwhelming increase of 352% of dengue cases during the same period of time. The larvicide efficacy, treatment of all in-use containers at the start of the monsoon season, together with treatment coverage of entire districts interrupted disease transmission in the temephos resistant province. PMID:27627758

  9. Bacterial Larvicide, Bacillus thuringiensis israelensis Strain AM 65-52 Water Dispersible Granule Formulation Impacts Both Dengue Vector, Aedes aegypti (L.) Population Density and Disease Transmission in Cambodia.

    Science.gov (United States)

    Setha, To; Chantha, Ngan; Benjamin, Seleena; Socheat, Doung

    2016-09-01

    A multi-phased study was conducted in Cambodia from 2005-2011 to measure the impact of larviciding with the bacterial larvicide, Bacillus thuringiensis israelensis (Bti), a water dispersible granule (WG) formulation on the vector, Aedes aegypti (L.) and the epidemiology. In our studies, all in-use containers were treated at 8 g/1000 L, including smaller containers and animal feeders which were found to contribute 23% of Ae aegypti pupae. The treated waters were subjected to routine water exchange activities. Pupal production was suppressed by an average 91% for 8 weeks. Pupal numbers continued to remain significantly lower than the untreated commune (UTC) for 13 weeks post treatment in the peak dengue vector season (p50% of the household in the UTC harbored ≥11 mosquitoes per home. The adult population continued to remain at significantly much lower numbers in the Bti treated commune than in the UTC for 10-12 weeks post treatment (p<0.05). In 2011, a pilot operational program was evaluated in Kandal Province, a temephos resistant site. It was concluded that 2 cycles of Bti treatment in the 6 months monsoon season with complete coverage of the target districts achieved an overall dengue case reduction of 48% in the 6 treated districts compared to the previous year, 2010. Five untreated districts in the same province had an overwhelming increase of 352% of dengue cases during the same period of time. The larvicide efficacy, treatment of all in-use containers at the start of the monsoon season, together with treatment coverage of entire districts interrupted disease transmission in the temephos resistant province.

  10. Eudragit(®) RS PO/RL PO as rate-controlling matrix-formers via roller compaction: Influence of formulation and process variables on functional attributes of granules and tablets.

    Science.gov (United States)

    Dave, Vivek S; Fahmy, Raafat M; Bensley, Dennis; Hoag, Stephen W

    2012-10-01

    The influence of plasticizer level, roll pressure and sintering temperature was investigated on the granule properties, tablet breaking force and theophylline release from tablets. Nine formulations using theophylline as a model drug, Eudragit(®) RL PO, Eudragit(®) RS PO, or both as a matrix former and triethyl citrate (TEC) as a plasticizer were prepared. The formulations were roller compacted and the granules obtained were evaluated for particle size distribution and flowability. These granules were compacted into tablets at a compression force of 7 kN. The tablets were thermally treated at different temperatures (50 and 75°C) for 5 h and were evaluated for breaking force and dissolution. Increase in roll pressure and TEC levels resulted in a progressive increase in the mean particle size of the granules. The flowability of the granules also improved with increasing roll pressures and TEC levels. Tablet breaking force increased with an increase in TEC levels and sintering temperatures. But these effects were significant only at the highest level of plasticizer and sintering temperature respectively. For the tablets containing Eudragit(®) RS PO, theophylline release decreased proportionately with increase in TEC levels and sintering temperatures. Tablets containing either Eudragit(®) RL PO or a mixture of RS PO and RL PO failed to impart an extended-release property to the tablets at the studied variables i.e. roll pressure, TEC levels and sintering temperature. It was clearly demonstrated that with suitable optimization of these parameters, the release-rate of a water soluble drug from the matrix tablets prepared via roller compaction can be finely controlled.

  11. Desvenlafaxine succinate monohydrate.

    Science.gov (United States)

    Venu, Nalivela; Sreekanth, Bukkapattanam R; Ram, Thaimattam; Devarakonda, Surya

    2008-05-01

    The title compound {systematic name: [2-(1-hydroxycyclohexyl)-2-(4-hydroxyphenyl)ethyl]dimethylammonium 3-carboxypropanoate monohydrate}, C(16)H(26)NO(2)(+) x C(4)H(5)O(4)(-) x H(2)O, is a succinate salt of O-desmethylvenlafaxine (desvenlafaxine). The present structure is one of four reported polymorphs of this salt, which is a new antidepressant drug. The carboxyl group of the succinate anion adopts a rare anti conformation and is engaged in a very short O-H...O(-) hydrogen-bond contact. Both cations and anions are involved separately in the formation of distinct O-H...O hydrogen-bonded networks. Desvenlafaxine cations and water molecules self-assemble to generate a honeycomb layer, while the succinate anions form a linear tape structure. These hydrogen-bonded networks are interlinked via N-H...O and O-H...O hydrogen bonds. The hydrogen-bonding network is so strong that desolvation and melting occur together at approximately 402 K. Thus, the crystal structure may be used to understand the thermal stability and solubility of the compound at the molecular level.

  12. FORMULATION AND EVALUATION OF CANDESARTAN CILEXETIL IMMEDIATE RELEASE TABLETS

    Directory of Open Access Journals (Sweden)

    Jampani Neeharika

    2012-07-01

    Full Text Available Candesartan Cilexetil is an esterified prodrug of Candesartan, a non-peptide angiotensin II type-1(AT1 receptor antagonist used in the treatment of hypertension and congestive heart failure. Candesartan meets the requirement of high potency but it is poorly absorbed when administered orally. Therefore, the prodrug Candesartan Cilexetil is developed. It is soluble in methylene chloride, half life is 5.1 to 10.5hrs and bioavailability is 15%. It is marketed as conventional tablets. In this work, it is formulated as immediate release tablets by changing the concentration of ingredients. For many drug substances, conventional immediate-release formulations provide clinically effective therapy while maintaining the required balance of pharmacokinetic and pharmacodynamic profiles with in acceptable level of safety to the patient. The immediate release formulation of Candesartan Cilexetil is prepared by wet granulation method to provide rapid onset of action. In order to optimize the best formulation, ten different trials are developed. The main ingredients used in the formulation are lactose monohydrate, PEG, calcium CMC and MCC. Weight variation, thickness, friability, disintegration time, in-vitro release, pharmaceutical assay are studied as response variables. The formulation containing 38% of MCC is selected as an optimized product in which the different physical properties and in-vitro release profile showed best comparable results with innovator product.

  13. Development of a fluid bed granulation design space using critical quality attribute weighted tolerance intervals.

    Science.gov (United States)

    Zacour, Brian M; Drennen, James K; Anderson, Carl A

    2012-08-01

    The fluid bed granulation and drying unit operation were used as a case study for control systems implementation. This single processor was used to blend, granulate, dry, and cool the materials. The current study demonstrated control of each of the phases using a fully automated, hybrid control system that incorporated first-principle modeling, empirical design of experiments (DOE), and process analytical technology to assure the production of constant product quality. The system allowed data to be collected efficiently for the development of a rigorous design space that combined formulation factors, process factors, and their interactions to define a tolerance surface where risk of future product failure was significantly reduced. The DOE incorporated microcrystalline cellulose and lactose monohydrate, excipients with substantially different wetting properties, to elucidate the relationship between the critical process parameters of the unit operation and the material properties of the formulation components. The extended analysis of covariance model enabled these factors and their interaction terms to be described in a single model. The results indicate that the development of a tolerance interval-based weighted design space can enhance product understanding and thereby help to assure future product quality.

  14. Sildenafil citrate monohydrate-cyclodextrin nanosuspension complexes for use in metered-dose inhalers.

    Science.gov (United States)

    Sawatdee, Somchai; Phetmung, Hirihattaya; Srichana, Teerapol

    2013-10-15

    Sildenafil is a selective phosphodiesterase-5 inhibitor used for the treatment of erectile dysfunction and pulmonary hypertension. Sildenafil citrate monohydrate was complexed with α-, hydroxypropyl-β- and γ-cyclodextrin (α-CD, HP-β-CD and γ-CD, respectively) to enhance its water solubility. The complexes of sildenafil citrate monohydrate with all types of CDs were characterized by phase solubility diagrams, (1)H and (13)C NMR, and dielectric constants. Sildenafil citrate monohydrate complexed with CDs was developed as nanosuspensions for use in a pressurized metered-dose inhaler (pMDI). Sildenafil citrate monohydrate pMDI formulations were prepared by a bottom-up process using dried ethanol as a solvent and HFA-134a as an antisolvent and propellant in order to form nanosuspensions. A 3×3 factorial design was applied for the contents of the dried ethanol and HFA-134a propellant. The phase solubility profiles of the sildenafil and cyclodextrins were described as AL type with a mole ratio 1:1. The piperazine moiety of sildenafil formed an inclusion in the cavity of the CDs. The particle diameters of the sildenafil citrate monohydrate suspensions in pMDIs were all within a nanosuspension size range. An assay of the sildenafil content showed that the formation of complexes with CDs was close to 100%. In the case of the formulations with CDs, the emitted doses varied within 97.4±10.8%, the fine particle fractions (FPFs) were in a range of 45-81%, the fine particle dose (FPD) was 12.6±2.0 μg and the mass median aerodynamic diameters (MMADs) were 1.86±0.41 μm. In contrast, the formulations without CDs produced a low emitted dose of sildenafil (<60%). Therefore, only sildenafil citrate monohydrate pMDI formulations containing CDs were suitable for use as aerosols.

  15. Statistical analysis and comparison of a continuous high shear granulator with a twin screw granulator: Effect of process parameters on critical granule attributes and granulation mechanisms.

    Science.gov (United States)

    Meng, Wei; Kotamarthy, Lalith; Panikar, Savitha; Sen, Maitraye; Pradhan, Shankali; Marc, Michaelis; Litster, James D; Muzzio, Fernando J; Ramachandran, Rohit

    2016-11-20

    This study is concerned with identifying the design space of two different continuous granulators and their respective granulation mechanisms. Performance of a continuous high shear granulator and a twin screw granulator with paracetamol formulations were examined by face-centered cubic design, which focused on investigating key performance metrics, namely, granule size, porosity, flowability and particle morphology of granules as a function of essential input process parameters (liquid content, throughput and rotation speed). Liquid and residence time distribution tests were also performed to gain insights into the liquid-powder mixing and flow behavior. The results indicated that continuous high shear granulation was more sensitive to process variation and produced spherical granules with monomodal size distribution and distinct internal structure and strength variation. Twin screw granulation with such a particular screw configuration showed narrower design space and granules were featured with multimodal size distribution, irregular shape, less detectible porosity difference and tighter range of strength. Granulation mechanisms explored on the basis of nucleation and growth regime maps revealed that for most cases liquid binder was uniformly distributed with fast droplet penetration into the powder bed and that granule consolidation and coalescence mainly took place in the nucleation, steady growth and rapid growth regimes.

  16. Sodium 2-mercaptoethanesulfonate monohydrate (coenzyme M sodium salt monohydrate

    Directory of Open Access Journals (Sweden)

    Stefan Mayr

    2008-11-01

    Full Text Available The 2-thioethanesulfonate anion is the smallest known coenzyme in nature (HS–CoM and plays a key role in methanogenesis by anaerobic archaea, as well as in the oxidation of alkenes by Gram-negative and Gram-positive eubacteria. The title compound, Na+·C2H5O3S2−·H2O, is the Na+ salt of HS–CoM crystallized as the monohydrate. Six O atoms form a distorted octahedral coordination geometry around the Na atom, at distances in the range 2.312 (4–2.517 (3 Å. Two O atoms of the sulfonate group, one O atom of each of three other symmetry-related sulfonate groups plus the water O atom form the coordination environment of the Na+ ion. This arrangement forms Na–O–Na layers in the crystal structure, parallel to (100.

  17. Preparation and evaluation of granules with pH-dependent release by melt granulation.

    Science.gov (United States)

    Shiino, Kai; Iwao, Yasunori; Fujinami, Yukari; Itai, Shigeru

    2012-07-15

    This study had two objectives: (1) to prepare, by melt granulation in a high-shear mixer, granules containing acetaminophen (APAP) as a model drug and aminoalkyl methacrylate copolymer E (AMCE) as a pH-sensitive polymer that readily dissolves at pH values lower than 5, and (2) to investigate the effects of AMCE loading (5-15%) on granule properties and the in vitro release profile of drug from the granules. Compared with polymer-free granules, the granules containing 5% and 10% AMCE were found to have higher median diameters and wider particle size distributions. For the formulation containing 15% AMCE, on the other hand, the diameters and distribution were similar to those for polymer-free granules. From compression testing, load-displacement curves revealed that AMCE enhanced particle strength at ambient temperature and induced plastic strain, while suppressing fragmentation of the granules. In addition, from dissolution testing using media with pH 4.0 and pH 6.5, granules containing AMCE, except 15% AMCE loading, exhibited drug release with significant pH dependence. When the pH 4.0 and pH 6.5 dissolution profiles were further compared by calculating the difference factor (f(1)), the 5% AMCE granules showed the strongest pH dependence of drug release among all formulations in this study. Large cracks and breakage were observed on the surface of 10% AMCE granules after they were used in dissolution testing. The obtained results are attributed to the plastic strain properties of AMCE above its glass transition temperature, and to the irregular distribution of AMCE within granules. Hence, this study has demonstrated for the first time that the combination of melt granulation and AMCE incorporation enables the formulation of novel functional granules that exhibit pH-dependent release of the active ingredient. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Distribution of binder in granules produced by means of twin screw granulation.

    Science.gov (United States)

    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.

  19. Twin screw granulation - review of current progress.

    Science.gov (United States)

    Thompson, M R

    2015-01-01

    Twin screw granulation (TSG) is a new process of interest to the pharmaceutical community that can continuously wet granulate powders, doing so at lower liquid concentrations and with better product consistency than found by a high shear batch mixer. A considerable body of research has evolved over the short time since this process was introduced but generally with little comparison of results. A certain degree of confidence has been developed through these studies related to how process variables and many attributes of machinery configuration will affect granulation but some major challenges still lay ahead related to scalability, variations in the processing regimes related to degree of channel fill and the impact of wetting and granulation of complex powder formulations. This review examines the current literature for wet granulation processes studied in twin screw extrusion machinery, summarizing the influences of operational and system parameters affecting granule properties as well as strives to provide some practical observations to newly interested users of the technique.

  20. Comparison of low shear, high shear, and fluid bed granulation during low dose tablet process development.

    Science.gov (United States)

    Hausman, Debra S

    2004-03-01

    Three processing methods were compared to develop a low dose (0.1%) immediate release tablet. Similar formulations were used to evaluate low shear, high shear, and fluid bed granulation methods. For each granulation process, the drug was dissolved or suspended in the granulating fluid and sprayed into the granulator. Both water and methanol were evaluated as granulating fluids. The low shear granulation was performed in a Patterson-Kelley V-Blender with I-bar. The high shear granulation was performed in a GRAL (top entry impeller) and a Diosna (bottom mounted impeller). Fluid bed granulation was also performed using top-spray. Acceptable content uniformity was obtained using each technology. The type of granulator and granulating solvent affected the granulation particle size distributions and bulk/tap densities. However, the addition of extragranular microcrystalline cellulose minimized the effect of variable granulation properties and allowed similar tablets to be produced from each granulation process.

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

    Science.gov (United States)

    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.

  2. Analysis of Pseudo-polymorphism Conversion of Theophylline During Wet Granulation and Drying Processes and Effect of Binder on Dehydration and Amorphization

    Science.gov (United States)

    Sakamoto, Tomoaki; Sasaki, Tetsuo; Katori, Noriko; Goda, Yukihiro

    2016-10-01

    We conducted a time-course analysis of the pseudo-polymorphism conversion (i.e., the hydration and dehydration) of the xanthine-related compound theophylline during wet granulation and drying processes, using terahertz spectroscopy. We also investigated the amorphization mechanism of theophylline hydrate during a drying process in a vacuum using terahertz, mid-infrared (mid-IR), and near-infrared (near-IR) spectroscopy. After a high-shear granulation process using a mixture of theophylline, hydroxypropyl cellulose (HPC), and water, the terahertz spectrum (which was similar to that of an anhydride) was changed to a spectrum that was quite similar to that of a monohydrate. This result suggests that (1) an anhydride was converted to a monohydrate during the wet granulation process and (2) the spectrum was changed to the original waveform after the drying process with heat. This phenomenon indicates that the theophylline monohydrate was reconverted to an anhydride during the drying process. When wet granules were dried in a vacuum, the terahertz absorption lessened and finally disappeared with the passage of time, suggesting that the theophylline monohydrate in the granules was converted to an amorphous state. During the drying process with heat, the dehydration progressed temperature dependently regardless of the presence/absence of HPC. In addition, the reconversion from a monohydrate to an anhydride was completed concurrently with the completion of dehydration. The conversion rate of theophylline from a monohydrate to an amorphous form in granules (with HPC) was faster than that without HPC. This observation suggests that HPC promotes the amorphization of theophylline.

  3. Twin screw granulation: steps in granule growth.

    Science.gov (United States)

    Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2012-11-15

    The present work focuses on the study of the progression of granules in different compartments along the length of screws in a twin screw granulator (TSG). The effects of varying powder feed rate; liquid to solid ratio and viscosity of granulation liquid on properties of granules was studied. The bigger granules produced at the start of the process were found to change in terms of size, shape and strength along the screw length at all the conditions investigated. The granules became more spherical and their strength increased along the screw length. Tracer granules were also introduced in order to understand the role of kneading and conveying elements in the TSG. The kneading elements promoted consolidation and breakage while the conveying elements led to coalescence, breakage and some consolidation. The results presented here help to provide a qualitative and quantitative understanding of the twin screw granulation process.

  4. A Search for Interstellar Monohydric Thiols

    Science.gov (United States)

    Gorai, Prasanta; Das, Ankan; Das, Amaresh; Sivaraman, Bhalamurugan; Etim, Emmanuel E.; Chakrabarti, Sandip K.

    2017-02-01

    It has been pointed out by various astronomers that a very interesting relationship exists between interstellar alcohols and the corresponding thiols (sulfur analog of alcohols) as far as the spectroscopic properties and chemical abundances are concerned. Monohydric alcohols such as methanol and ethanol are widely observed and 1-propanol was recently claimed to have been seen in Orion KL. Among the monohydric thiols, methanethiol (chemical analog of methanol) has been firmly detected in Orion KL and Sgr B2(N2) and ethanethiol (chemical analog of ethanol) has been observed in Sgr B2(N2), though the confirmation of this detection is yet to come. It is very likely that higher order thiols could be observed in these regions. In this paper, we study the formation of monohydric alcohols and their thiol analogs. Based on our quantum chemical calculation and chemical modeling, we find that the Tg conformer of 1-propanethiol is a good candidate of astronomical interest. We present various spectroscopically relevant parameters of this molecule to assist in its future detection in the interstellar medium.

  5. Granulation of fine powder

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Ching-Fong

    2016-08-09

    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 form a dense compact with a higher density and more uniform pore size distribution.

  6. Influence of crystal form of ipratropium bromide on micronisation and aerosolisation behaviour in dry powder inhaler formulations.

    Science.gov (United States)

    Shur, Jagdeep; Kubavat, Harshal A; Ruecroft, Graham; Hipkiss, David; Price, Robert

    2012-09-01

    This study aimed to investigate the relationship between the mechanical properties of anhydrous and monohydrate ipratropium bromide (IB) crystals, their processing behaviour upon air-jet micronisation and aerosolisation performance in dry powder inhaler (DPI) formulations. IB monohydrate and anhydrous crystals were produced from seed crystals and supercritical carbon dioxide crystallisation, respectively. Young's modulus of anhydrous and monohydrate IB crystals was determined using nanoindentation. For air-jet micronised crystals, the physicochemical and surface interfacial properties via the cohesive-adhesive balance (CAB) approach were investigated. These data were correlated to in-vitro aerosolisation performance of carrier-based DPI formulations containing either anhydrous or monohydrate IB. Particle size and Young's modulus of both crystals were similar and this was reflected in their similar processing upon micronisation. Particle size of micronised anhydrous and monohydrate crystals were similar. CAB measurements of the micronised particles of monohydrate or anhydrous forms of IB with respect to lactose were 0.70 (R² = 0.998) and 0.77 (R² = 0.999), respectively. These data suggested that both samples had similar adhesion to lactose, which correlated with their similar in-vitro aerosolisation performance in DPI formulations. Monohydrate and anhydrous crystals of IB exhibited similar mechanical properties and interfacial properties upon secondary processing. As a result, the performance of the DPI formulations were similar. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

  7. 21 CFR 520.608 - Dicloxacillin sodium monohydrate capsules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Dicloxacillin sodium monohydrate capsules. 520.608 Section 520.608 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Dicloxacillin sodium monohydrate capsules. (a) Specifications. Each capsule contains dicloxacillin sodium...

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

    National Research Council Canada - National Science Library

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

    2015-01-01

    ...%) 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...

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

    Science.gov (United States)

    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.

  10. Granule size distributions after twin-screw granulation - Do not forget the feeding systems.

    Science.gov (United States)

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

    2016-09-01

    The aim of this study was to investigate the influence of qualitatively different powder feeder performances on resulting granule size distributions after twin-screw granulation of a highly drug loaded, hydrophobic mixture and a mannitol powder. It was shown that powder feeder related problems usually cannot be identified by trusting in the values given by the feeder. Therefore, a newly developed model for the evaluation of the performance of powder feeders was introduced and it was tried to connect this model to residence time distributions in twin-screw granulation processes. The influence of feeder performances on resulting granule size distributions varied, depending on the applied screw configuration and the used powder. Regarding the hydrophobic and highly drug loaded formulation, which was granulated at an L/S-ratio of 0.5, a pure conveying screw and a medium kneading configuration, consisting of 60° kneading blocks were negatively influenced by poor feeder settings. For optimal settings more narrow distributions could be obtained. For an extensive kneading configuration good and poor settings resulted in mono-modal granule size distributions but were differing in the overall size. Mannitol, a model substance for a liquid sensitive formulation was granulated at an L/S-ratio of 0.075. It was even more important to maintain optimal feeding as mannitol was highly affected by poor feeder performances. Even an extensive kneading configuration could not level the errors in powder feeder performance, resulting in qualitatively different granule size distributions. The results of this study demonstrate the importance of detailed knowledge about applied feeding systems to gain optimal performance in twin-screw granulation.

  11. Drug distribution in wet granulation: foam versus spray.

    Science.gov (United States)

    Tan, Melvin X L; Nguyen, Thanh H; Hapgood, Karen P

    2013-09-01

    Foam granulation technology is a new wet granulation approach for pharmaceutical formulations. This study evaluates the performance of foam and spray granulation in achieving uniform drug distribution using a model formulation. To observe wetting and nuclei formation, single drop/foam penetration experiments were performed on a static powder bed comprised of varying compositions of hydrophilic/hydrophobic glass ballotini, and hydrophilic lactose/hydrophobic salicylic acid respectively. High shear granulation experiments were performed in a 5L mixer using varying compositions of hydrophilic lactose and hydrophobic salicylic acid. Four percent hydroxylpropyl methylcellulose (HPMC) solution was delivered at 90 g/min as either a foam (92% FQ) or an atomized spray whilst recording impeller power consumption. After drying, the granule size distribution was measured and the granule composition was estimated using gravimetric filtration in methanol. Foam penetration was less dependent on the powder hydrophobicity compared to drop penetration. For glass ballotini powder mixtures, foam induced nucleation created nuclei with relatively uniform structure and size regardless of the powder hydrophobicity. For salicylic acid and lactose mixtures, increasing the proportion of salicylic acid reduced the nuclei granule size for both foam and drop binder addition. The granule drug distribution was not significantly affected by the binder addition method. Processing conditions, including liquid binder amount, impeller speed, wet massing, and the wettability properties of the formulation were the dominant factors for delivering homogeneous granules. The study reveals that foam and spray granulation involve different nucleation mechanisms - spray tends to incur early liquid penetration whereas foam granulation operates well in mechanical dispersion.

  12. Relative bioavailability of three formulations of galunisertib administered as monotherapy in patients with advanced or metastatic cancer

    Directory of Open Access Journals (Sweden)

    Ivelina Gueorguieva

    2016-12-01

    Full Text Available Objective: Galunisertib (LY2157299 monohydrate, an inhibitor of the transforming growth factor β (TGFβ pathway, is currently under investigation in several clinical trials involving multiple tumor types. The primary objective of this study was to assess relative bioavailability of two new galunisertib formulations developed using the roller compaction (RC dry-milled (RCD and RC slurry-milled (RCS processes, compared with the existing formulation developed using the high-sheer wet granulation (HSWG process. The secondary objective was to report the safety profile after a single dose of the three formulations. Methods: Patients with advanced or metastatic cancer were enrolled into this single-center, 3-period, 6-sequence crossover study. Patients were assigned sequentially to 1 of 6 sequences in blocks of 6 to ensure that all 6 sequences have the same number of completers. A patient entering a sequence received a different galunisertib formulation as a single 150 mg dose orally during each of the 3 periods. Each period was separated from the next by a washout interval of at least 48 hours. Pharmacokinetic (PK parameters, including area under curve (AUC and Cmax, were computed using standard non-compartmentalized methods of analysis. For comparison of exposures between formulations, log-transformed AUC and Cmax values were analyzed using a linear mixed-effects model. Safety assessments included adverse event monitoring, physical examinations, and laboratory tests. Results: Of the 14 patients who entered and completed the study, 13 patients were included in the final statistical analysis. AUC(0-tlast, AUC(0-48 h, and AUC(0-∞ for the RC formulations and the HSWG formulation were similar. Cmax was reduced by approximately 22% and tmax was longer by at least 1.00 h for the RCD and RCS formulations compared with the HSWG formulation. The RC formulations demonstrated a safety profile after a single dose similar to the HSWG formulation. Conclusions

  13. Distribution of binder in granules produced by means of twin screw granulation

    DEFF Research Database (Denmark)

    Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen

    2014-01-01

    -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....

  14. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers...... in a monoclinic cholesterol . H2O phase, has been monitored and their structures characterized to near atomic resolution. Crystallographic evidence is presented that this multilayer phase is similar to that of a reported metastable cholesterol phase of undetermined structure obtained from bile before...... transformation to the triclinic phase of cholesterol . H2O, the thermodynamically stable macroscopic form. According to grazing incidence x-ray diffraction measurements and crystallographic data, a transformation from the monoclinic film structure to a multilayer of the stable monohydrate phase involves...

  15. 2-Methyl­aspartic acid monohydrate

    OpenAIRE

    Brewer, Greg; Burton, Aaron S.; Dworkin, Jason P.; Butcher, Ray J.

    2013-01-01

    The title compound, C5H9NO4·H2O, is an isomer of the α-amino acid glutamic acid that crystallizes from water in its zwitterionic form as a monohydrate. It is not one of the 20 proteinogenic α-amino acids that are used in living systems and differs from the natural amino acids in that it has an α-methyl group rather than an α-H atom. In the crystal, an O—H⋯O hydrogen bond is present between the acid and water mol­ecules while extensive N—H⋯O and O—H⋯O hydrogen bonds link the components into a ...

  16. Mining the granule proteome

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Goetze, Jens P; Johnsen, Anders H

    2015-01-01

    Proteomics of secretory granules is an emerging strategy for identifying secreted proteins, including potentially novel candidate biomarkers and peptide hormones. In addition, proteomics can provide information about the abundance, localization and structure (post-translational modification) of g...

  17. The relation between granule size, granule stickiness, and torque in the high-shear granulation process

    NARCIS (Netherlands)

    Bouwman, A.M.; Henstra, M.J.; Hegge, J.J.M.E.; Zhang, Z.; Ingram, A.; Seville, J.P.K.; Frijlink, H.W.

    2005-01-01

    Purpose. To investigate the background of the observed relationship between measured torque and granule size in high-shear granulation processes. Methods. Torque was measured during the granulation process; the behavior of individual wet granules during compaction was investigated using micromanipul

  18. Quantitative Assessment of Mass Flow Boundaries in Continuous Twin-screw Granulation.

    Science.gov (United States)

    Schmidt, Adrian; de Waard, Hans; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

    2016-01-01

    In pharmaceutical manufacturing, there is an increasing interest in continuous manufacturing. As an example for fast continuous processes in general of considerable complexity, this study was focussed on improving the understanding of twin-screw wet granulation. The impact of the liquid-to-solid (L/S) mass flow ratio on product quality (granules) as well as on downstream process operations (tableting) was investigated in detail. Initially two methods were used to define L/S ratio boundaries for the granulation regime in twin-screw wet granulation. It was shown that the first method, which is based on measuring the wet granule mass flow variation, can be used to define the upper L/S ratio boundary of the granulation regime. The second method, based on measuring the granule size distribution, can be used to define the lower L/S ratio boundary of the regime. Using these methods, the granulation regime for different formulations could be established. This information was then used to show that the formulation could be optimised such that the process is more robust (i.e. wider L/S ratio boundaries for the granulation regime). Also it could be used to optimise the formulation considering further downstream processing such as drying (using as little water as possible to reduce drying efforts) or tableting (obtain granules with optimised tableting properties). Preferably, the process should be performed close to the lower L/S ratio boundary of the granulation regime. In summary, these tools enabled the quantitative establishment of granulation regime boundaries in a twin-screw wet granulation process and can be used to optimise formulation and to create a robust process. Analogies to other continuous processes in completely different applications can be conceived.

  19. The influence of excipients on the stability of the moisture sensitive drugs aspirin and niacinamide: comparison of tablets containing lactose monohydrate with tablets containing anhydrous lactose.

    Science.gov (United States)

    Du, J; Hoag, S W

    2001-01-01

    The purpose of this study is to test the hypothesis that in tablet formulations, moisture-sensitive drugs formulated with lactose monohydrate have the same stability as formulations containing anhydrous lactose, and to characterize the kinetics of niacinamide degradation in the solid state. Aspirin and niacinamide decomposition were used as indicators of stability. Aspirin and niacinamide tablets containing either lactose monohydrate or anhydrous lactose were separately investigated at different temperatures and relative humidities; the stability tests were done at 25 degrees C--60% RH, 40 degrees C--80% RH, 60 degrees C--60% RH, 60 degrees C--80% RH, and 80 degrees C--80% RH. Official U.S. Pharmacopeia methods were used for the aspirin and niacinamide assays. Statistical analysis showed that tablets containing lactose monohydrate have the same stability as tablets containing anhydrous lactose, which means that even though water is present in the crystal structure, the bound water does not influence the reaction rate. In addition, niacinamide degradation in the solid-state can be described by a third order rate equation.

  20. Molecular Structure of Aminoguanidine Sulfate Monohydrate

    Institute of Scientific and Technical Information of China (English)

    CHEN Hong-yan; ZHANG Tong-lai; QIAO Xiao-jing; YANG Li; SHAO Feng-lei

    2006-01-01

    The single crystal of aminoguanidine sulfate monohydrate [(AG)2SO4·H2O] is obtained and its structure is determined by X-ray diffraction analysis. The compound crystallizes in orthorhombic system with space group Pnma and the empirical formula C2H16N8O5S. The unit cell parameters are as follows: a=0.6759(2)nm, b=1.4131(5)nm, c=1.1650(4)nm, V=1.1128(6)n m3, Z=4, Dc=1.578g/cm3, F(000)=560, s=1.069, μ(MoKα)=0.318mm-1. The final R and Wr are 0.0312 and 0.0833, respectively. The title compound is an ionic compound and its structure unit consists of two aminoguanidium cations, one sulfate anion and one crystal water molecule, which are interconnected by electrostatic forces and hydrogen bond s into net structure, making the title compound very stable. Under a linear heat ingrate, the thermal decomposition processes of (AG)2SO4·H2O have one en dothermal dehydration stage, one melting process and one exothermic decomposition stage at 50-400℃, and can evolve abundant gas products.

  1. [Thermostability testing of iron(II) sulphate for formulation of drug product].

    Science.gov (United States)

    Laczkovich, Orsolya; Révész, Piroska; Pallagi, Edina; Eros, István

    2003-01-01

    The aim of the experimental study was to determine which iron(II) sulphate form, the monohydrate or the heptahydrate, is more suitable for formulation of a retard dosage form with melt technology, and to control the suitable compound from a thermostability aspect according to the ICH (International Conference on Harmonization). Iron(II) sulphate is susceptible to oxidation and a rise in temperature increases the rate of this redox change. The presence of Fe3+ is definitely harmful in the case of enteral administration. First, the activation energy of the oxidation process was quantified for both iron(II) sulphate forms. It was found that the monohydrate is oxidized four times more slowly than the monohydrate form. It follows from this that the monohydrate well resists short-lived high temperature. The thermostability tests on the monohydrate showed that samples, stored at high temperature and high relative humidity for a long time, oxidized only slowly. On the basis of all these findings, the monohydrate form may be suggested for melt technology.

  2. The tetrapeptide Z-Leu-Aib-Pro-Val-OBg monohydrate.

    Science.gov (United States)

    Gessmann, Renate; Schiemann, Norbert; Brückner, Hans; Petratos, Kyriacos

    2003-08-01

    The intramolecular hydrogen-bonding pattern of Z-Leu-Aib-Pro-Val-OBg monohydrate [(N-benzhydrylamino)carbonylmethyl N-benzyloxycarbonyl-alpha-aminoisobutyrylprolylvalinate monohydrate], C(43)H(55)N(5)O(8).H(2)O, is unusual for a tetrapeptide because, in addition to a 1-->4 hydrogen bond, a second hydrogen bond of the type 1-->5 is formed. This folding reflects the intramolecular hydrogen-bonding pattern that this amino acid sequence adopts in the naturally occurring peptaibol alamethicin.

  3. Brushite-based calcium phosphate cement with multichannel hydroxyapatite granule loading for improved bone regeneration.

    Science.gov (United States)

    Sarkar, Swapan Kumar; Lee, Byung Yeol; Padalhin, Andrew Reyas; Sarker, Avik; Carpena, Nathaniel; Kim, Boram; Paul, Kallyanshish; Choi, Hwan Jun; Bae, Sang-Ho; Lee, Byong Taek

    2016-01-01

    In this work, we report brushite-based calcium phosphate cement (CPC) system to enhance the in vivo biodegradation and tissue in-growth by incorporation of micro-channeled hydroxyapatite (HAp) granule and silicon and sodium addition in calcium phosphate precursor powder. Sodium- and silicon-rich calcium phosphate powder with predominantly tri calcium phosphate (TCP) phase was synthesized by an inexpensive wet chemical route to react with mono calcium phosphate monohydrate (MCPM) for making the CPC. TCP nanopowder also served as a packing filler and moderator of the reaction kinetics of the setting mechanism. Strong sintered cylindrical HAp granules were prepared by fibrous monolithic (FM) process, which is 800 µm in diameter and have seven micro-channels. Acid sodium pyrophosphate and sodium citrate solution was used as the liquid component which acted as a homogenizer and setting time retarder. The granules accelerated the degradation of the brushite cement matrix as well as improved the bone tissue in-growth by permitting an easy access to the interior of the CPC through the micro-channels. The addition of micro-channeled granule in the CPC introduced porosity without sacrificing much of its compressive strength. In vivo investigation by creating a critical size defect in the femur head of a rabbit model for 1 and 2 months showed excellent bone in-growth through the micro-channels. The granules enhanced the implant degradation behavior and bone regeneration in the implanted area was significantly improved after two months of implantation.

  4. Wet granulation in a twin-screw extruder: implications of screw design.

    Science.gov (United States)

    Thompson, M R; Sun, J

    2010-04-01

    Wet granulation in twin-screw extrusion machinery is an attractive technology for the continuous processing of pharmaceuticals. The performance of this machinery is integrally tied to its screw design yet little fundamental knowledge exists in this emerging field for granulation to intelligently create, troubleshoot, and scale-up such processes. This study endeavored to systematically examine the influence of different commercially available screw elements on the flow behavior and granulation mechanics of lactose monohydrate saturated at low concentration (5-12%, w/w) with an aqueous polyvinyl-pyrrolidone binder. The results of the work showed that current screw elements could be successfully incorporated into designs for wet granulation, to tailor the particle size as well as particle shape of an agglomerate product. Conveying elements for cohesive granular flows were shown to perform similar to their use in polymer processing, as effective transport units with low specific mechanical energy input. The conveying zones provided little significant change to the particle size or shape, though the degree of channel fill in these sections had a significant influence on the more energy-intensive mixing elements studied. The standard mixing elements for this machine, kneading blocks and comb mixers, were found to be effective for generating coarser particles, though their mechanisms of granulation differed significantly.

  5. 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.

    Science.gov (United States)

    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.

  6. Structural information from OH stretching frequencies monohydric saturated alcohols

    NARCIS (Netherlands)

    Maas, J.H. van der; Lutz, E.T.G.

    1974-01-01

    Infrared data have been recorded of the hydroxyl stretching band for about 70 monohydric saturated alcohols in dilute carbon tetrachloride solution. The wavenumber maximum, the half-bandwidth and the band pattern could be related to the structure of the molecules. Not only primary, secondary and ter

  7. Study growth kinetics in fluidized bed granulation with at-line FBRM.

    Science.gov (United States)

    Hu, Xinhui; Cunningham, John C; Winstead, Denita

    2008-01-22

    In this study, a novel at-line focused beam reflectance measurement (FBRM) technique was developed to investigate granule growth in a fluidized bed granulation (FBG). The chord length distribution (CLD) measured by the FBRM was used to represent granule particle size distribution (PSD). Through a systematic study, it was proved that the trends of the chord length measured by the at-line FBRM technique were identical to those measured by a laser diffraction instrument and sieve analysis in spite of different measurement mechanisms. The portable at-line FBRM technique was successfully applied to a granule growth kinetics study for a fluidized bed granulation performed in a Glatt GPCG-1 granulator. Granule size evolution was clearly exhibited by the at-line FBRM. Spray rate was found to be the most significant factor on the granule growth compared with the other two factors: binder solution concentration and intra- to extra-granular microcrystalline cellulose (MCC) ratio for the formulation studied in this work. The CLD evolution measured by the FBRM confirmed that the granule agglomeration was mainly dominated by the binder on the granule surface. The at-line FBRM enables us to select appropriate process parameters and effectively control the fluid bed granulation process.

  8. Crystal structures of ethylene glycol and ethylene glycol monohydrate.

    Science.gov (United States)

    Fortes, A Dominic; Suard, Emmanuelle

    2011-12-21

    We have carried out a neutron powder diffraction study of deuterated ethylene glycol (1,2-ethanediol), and deuterated ethylene glycol monohydrate with the D2B high-resolution diffractometer at the Institut Laue-Langevin. Using these data, we have refined the complete structure, including all hydrogen atoms, of the anhydrous phase at 220 K. In addition, we have determined the structure of ethylene glycol monohydrate at 210 K using direct space methods. Anhydrous ethylene glycol crystallizes in space-group P2(1)2(1)2(1) with four formula units in a unit-cell of dimensions a = 5.0553(1) Å, b = 6.9627(1) Å, c = 9.2709(2) Å, and V = 326.319(8) Å(3) [ρ(calc)(deuterated) = 1386.26(3) kg m(-3)] at 220 K. Ethylene glycol monohydrate crystallizes in space-group P2(1)/c with four formula units in a unit-cell of dimensions a = 7.6858(3) Å, b = 7.2201(3) Å, c = 7.7356(4) Å, β = 92.868(3)°, and V = 428.73(2) Å(3) [ρ(calc)(deuterated) = 1365.40(7) kg m(-3)] at 210 K. Both the structures are characterized by the gauche conformation of the ethylene glycol molecule; however, the anhydrous phase contains the tGg' rotamer (or its mirror, g'Gt), whereas the monohydrate contains the gGg' rotamer. In the monohydrate, each water molecule is tetrahedrally coordinated, donating two hydrogen bonds to, and accepting two hydrogen bonds from the hydroxyl groups of neighboring ethylene glycol molecules. There are substantial differences in the degree of weak C-D···O hydrogen bonding between the two crystals, which calls into question the role of these interactions in determining the conformation of the ethylene glycol molecule.

  9. Antioxidant activity of carbocysteine lysine salt monohydrate.

    Science.gov (United States)

    Pinamonti, S; Venturoli, L; Leis, M; Chicca, M; Barbieri, A; Sostero, S; Ravenna, F; Daffonchio, L; Novellini, R; Ciaccia, A

    2001-09-01

    Reactive oxygen radicals are involved in many respiratory diseases, including chronic obstructive pulmonary disease (COPD). Carbocysteine lysine salt monohydrate (CLS) is a mucoactive drug effective in the treatment of bronchopulmonary diseases characterized by mucus alterations, including COPD. In the present study, the antioxidant activity of CLS was studied in vitro in three different oxygen radical producing systems, i.e. bronchoalveolar lavages (BAL) from patients affected by COPD, ultrasound treated human serum and cultured human lung endothelial cells challenged with elastase. BAL, exposed or not to different concentrations of CLS (1.5-30 mM), was assayed for free radical content by fluorometric analysis of DNA unwinding (FADU) or by cytochrome c reduction kinetics. Human serum was treated with ultrasound in the presence or absence of CLS (1.5, 2.5 mM) or N-acetyl cysteine (NAC; 4, 5 mM) and assayed for free radical content by FADU. Human endothelial cells cultured in vitro from pulmonary artery were incubated with elastase (0.3 IU/mL), in the presence or absence of glutathione (GSH; 0.65 mM) or CLS (0.16 mM). The supernatant was tested for cytochrome c reduction kinetics whereas cell homogenates were assessed for xanthine oxidase (XO) content by SDS-PAGE. Results showed that CLS is more effective as an in vitro scavenger in comparison to GSH and NAC. CLS reduced the damage of DNA from healthy donors exposed to COPD-BAL and was able to quench clastogenic activity induced in human serum by exposure to ultrasound at concentrations as low as 2.5 mM. NAC protect DNA from radical damage, starting from 5 mM. In human lung endothelial cells cultured in presence of elastase, CLS (0.16 mM) decreased xanthine oxidase activity. These results suggest that CLS could act by interfering with the conversion of xanthine dehydrogenase into superoxide-producing xanthine oxidase. The antioxidant activity of CLS could contribute to its therapeutic activity by reducing radical

  10. A novel methodology to study polymodal particle size distributions produced during continuous wet granulation.

    Science.gov (United States)

    Mendez Torrecillas, Carlota; Halbert, Gavin W; Lamprou, Dimitrios A

    2017-03-15

    It is important during powder granulation to obtain particles of a homogeneous size especially in critical situations such as pharmaceutical manufacture. To date, homogeneity of particle size distribution has been defined by the use of the d50 combined with the span of the particle size distribution, which has been found ineffective for polymodal particle size distributions. This work focuses on demonstrating the limitations of the span parameter to quantify homogeneity and proposes a novel improved metric based on the transformation of a typical particle size distribution curve into a homogeneity factor which can vary from 0 to 100%. The potential of this method as a characterisation tool has been demonstrated through its application to the production of granules using two different materials. The workspace of an 11mm twin screw granulator was defined for two common excipients (α-lactose monohydrate and microcrystalline cellulose). Homogeneity of the obtained granules varied dramatically from 0 to 95% in the same workspace, allowing identification of critical process parameters (e.g. feed rate, liquid/solid ratio, torque velocities). In addition it defined the operational conditions required to produce the most homogeneous product within the range 5μm-2.2mm from both materials.

  11. Isolation of RNP granules

    DEFF Research Database (Denmark)

    Jønson, Lars; Nielsen, Finn Cilius; Christiansen, Jan

    2011-01-01

    be regarded as a supramolecular assembly of RNA and protein, probably representing several overlapping post-transcriptional operons. The present protocol describes how RNP granules may be isolated by the transgenic expression of a 3X FLAG version of an RNA-binding protein under tetracycline control via...... the tetracycline receptor/operator complex. In this way, inclusion of an appropriate tetracycline concentration ensures expression of the tagged version at the endogenous level, and the 3X FLAG tag is a convenient "handle" for the subsequent immunoprecipitation by immobilized anti-FLAG antibody....

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

    Science.gov (United States)

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

    2017-02-15

    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

  13. Effects of change in the formulation of lanthanum carbonate on laboratory parameters.

    Science.gov (United States)

    Takita, Takako; Furuhashi, Mitsuyoshi; Fujimoto, Taiki; Suzuki, Hiroo; Harada, Masaki; Maruyama, Satoshi; Tamiya, Rika; Kamiya, Eri; Okamoto, Mari; Tukada, Atsuyo; Furuhashi, Mikako; Kato, Akihiko

    2014-06-01

    Lanthanum carbonate (LC) is available in the two formulations of chewable tablets and granules. In this study, we changed the formulation of LC from chewable tablet to granules, and compared the laboratory parameters for 3 months before and after changing formulation in 58 hemodialysis (HD) patients. We also surveyed patients about their preferences for the two formulations. The mean serum phosphorus (P) levels decreased significantly (P calcium levels also increased significantly (P tablets. These findings suggest that changing the formulation of LC to granules may reduce serum P levels of the HD patients in clinical practices.

  14. Granulation techniques and technologies: recent progresses.

    Science.gov (United States)

    Shanmugam, Srinivasan

    2015-01-01

    Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dust-free granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical properties such as granule size, bulk density, porosity, hardness, moisture, compressibility, etc. together with physical and chemical stability of the drug. Granulation process can be divided into two types: wet granulation that utilize a liquid in the process and dry granulation that requires no liquid. The type of process selection requires thorough knowledge of physicochemical properties of the drug, excipients, required flow and release properties, to name a few. Among currently available technologies, spray drying, roller compaction, high shear mixing, and fluid bed granulation are worth of note. Like any other scientific field, pharmaceutical granulation technology also continues to change, and arrival of novel and innovative technologies are inevitable. This review focuses on the recent progress in the granulation techniques and technologies such as pneumatic dry granulation, reverse wet granulation, steam granulation, moisture-activated dry granulation, thermal adhesion granulation, freeze granulation, and foamed binder or foam granulation. This review gives an overview of these with a short description about each development along with its significance and limitations.

  15. Granule Size Distribution and Porosity of Granule Packing

    Institute of Scientific and Technical Information of China (English)

    DAI Shu-hua; SHEN Feng-man; YU Ai-bing

    2008-01-01

    The granule size distribution and the porosity of the granule packing process were researched.For realizing the optimizing control of the whole sintering production process,researchers must know the factors influencing the granule size distribution and the porosity.Therefore,tests were carried out in the laboratory with regard to the influences of the size and size distribution of raw materials and the total moisture content on the size and size distribution of granule.Moreover,tests for finding out the influences of the moisture content and the granule volume fraction on the porosity were also carried out.The results show that (1) the raw material has little influence on granulation when its size is in the range of 0.51 mm to 1.0 mm;(2) the influence of the material size on granule size plays a dominant role,and in contrast,the moisture content creates a minor effect on granule size;(3) in binary packing system,with the increase in the constituent volume fraction,the porosity initially increases and then decreases,and there is a minimum value on the porosity curve of the binary mixture system;(4) the minimum value of the porosity in binary packing system occurs at different locations for different moisture contents,and this value shifts from right to left on the porosity curve with increasing the moisture content;(5) the addition of small granules to the same size component cannot create a significant influence on the porosity,whereas the addition of large granules to the same system can greatly change the porosity.

  16. Formulation of Extended-Release Metformin Hydrochloride Matrix ...

    African Journals Online (AJOL)

    Erah

    carrier, polymer and preparation method on metformin release from the formulations in vitro as well as ... Results: The physicochemical characteristics of all the granules and tablets were generally satisfactory. Optimization ..... Some physical.

  17. Multidimensional modelling of anaerobic granules

    DEFF Research Database (Denmark)

    Picioreanu, C.; Batstone, Damien J.; van Loosdrecht, M.C.M.

    2005-01-01

    . The model uses individual-based representation of biomass particles within the granule (biofilm), and describes spreading by an iterative pushing technique. The overall computational domain consists of one granule, and is divided into a grid with Cartesian coordinates. The number of grid elements does...

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

    Science.gov (United States)

    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.

  19. Granulated zeolite plant "Alusil", Zvornik

    Directory of Open Access Journals (Sweden)

    Stanković Mirjana S.

    2003-01-01

    Full Text Available The IGPC's Engineering Department designed basic technological and machine projects for a granulated zeolite production plant, on the basis of which a pilot plant with an initial capacity of 5,000 t/y was constructed in 1984, within Birač - Zvornik production complex. The technology in these projects was developed in the laboratories of the IGPC.Several goals were realized by designing a granulated zeolite production plant. This technology is one of the newest state of the art high tech technologies. The product meets all quality demands, as well as environmental regulations, by which granulated zeolite production for various uses was developed. The granulated zeolite production process is fully automatized, and the product has uniform quality. There is no waste material in granulated zeolite production, because all products with unsatisfactory quality are returned to the process. The production process can be controlled manually, which is necessary during start - up, and repairs.

  20. Moluo Yangping Granule (

    Institute of Scientific and Technical Information of China (English)

    LI; En-fu

    2001-01-01

    Peptic ulcer is a common and frequently encountered disease. H2 receptor blocker and several other drugs have been used in treating peptic ulcer (PU) since many years ago, but there still remain a rather large number of intractable ulcer and recurrent ulcer. Recently the discovery of Helicobacter pylori (HP), as well as the relationship between HP and PU relapse was confirmed, but there still lacks of perfect therapeutic program for anti-HP infection(1). From June 1993 to August 1996, we used a pure TCM preparation Moluo Yangping granule (摩罗疡平冲剂, MYG) in treating 64 PU patients, and satisfactory results have been obtained. The report is as follows.

  1. 21 CFR 524.1610 - Orbifloxacin, mometasone furoate monohydrate, and posaconazole suspension.

    Science.gov (United States)

    2010-04-01

    ... posaconazole suspension. 524.1610 Section 524.1610 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... DOSAGE FORM NEW ANIMAL DRUGS § 524.1610 Orbifloxacin, mometasone furoate monohydrate, and posaconazole... furoate monohydrate equivalent to 1 mg mometasone furoate, and 1 mg posaconazole. (b) Sponsor. See...

  2. Fabrication and cytocompatibility of spherical magnesium ammonium phosphate granules.

    Science.gov (United States)

    Christel, Theresa; Geffers, Martha; Klammert, Uwe; Nies, Berthold; Höß, Andreas; Groll, Jürgen; Kübler, Alexander C; Gbureck, Uwe

    2014-09-01

    Magnesium phosphate compounds, as for example struvite (MgNH4PO4·6H2O), have comparable characteristics to calcium phosphate bone substitutes, but degrade faster under physiological conditions. In the present work, we used a struvite forming calcium doped magnesium phosphate cement with the formulation Ca0.75Mg2.25(PO4)2 and an ammonium phosphate containing aqueous solution to produce round-shaped granules. For the fabrication of spherical granules, the cement paste was dispersed in a lipophilic liquid and stabilized by surfactants. The granules were characterized with respect to morphology, size distribution, phase composition, compressive strength, biocompatibility and solubility. In general, it was seen that small granules can hardly be produced by means of emulsification, when the raw material is a hydraulic paste, because long setting times promote coalescence of initially small unhardened cement droplets. Here, this problem was solved by using an aqueous solution containing both the secondary (NH4)2HPO4 and primary ammonium phosphates NH4H2PO4 to accelerate the setting reaction. This resulted in granules with 97 wt.% having a size in the range between 200 and 1,000 μm. The novel solution composition doubled the compressive strength of the cement to 37 ± 5 MPa without affecting either the conversion to struvite or the cytocompatibility using human fetal osteoblasts.

  3. Antifeedant, larvicidal and growth inhibitory effects of ononitol monohydrate isolated from Cassia tora L. against Helicoverpa armigera (Hub.) and Spodoptera litura (Fab.) (Lepidoptera: Noctuidae).

    Science.gov (United States)

    Baskar, Kathirvelu; Ignacimuthu, Savarimuthu

    2012-07-01

    Ononitol monohydrate isolated from the ethyl acetate extract of Cassia tora L. using column chromatography was evaluated for its antifeedant, larvicidal and growth inhibitory activities against Helicoverpa armigera and Spodoptera litura at different concentrations of 125, 250, 500 and 1000 ppm. Leaf disc no-choice method was used for the bioassay. The compound showed significant antifeedant, larvicidal and pupicidal activities against H. armigera and S. litura. The compound also prolonged the larval-pupal duration of the insect at all the tested concentrations. The activities were concentration dependent for both the insects. Ononitol could be used as an agent to prepare botanical new pesticidal formulations.

  4. Clarithromycin monohydrate: a synchrotron X-ray powder study

    Directory of Open Access Journals (Sweden)

    Shigeru Itai

    2012-03-01

    Full Text Available In the crystal structure of the title compound, clarithromycin (CAM monohydrate, C38H69NO13·H2O, the water molecule behaves as a proton donor and is hydrogen bonded to the hydroxy O atom of the CAM cladinose ring. The hydroxy O atom also behaves as a proton donor, forming an intermolecular hydrogen bond with one of the hydroxy groups of the 14-membered aglycone ring. The CAM molecules are linked through these hydrogen bonds into chains running parallel to the c axis.

  5. Clarithromycin monohydrate: a synchrotron X-ray powder study.

    Science.gov (United States)

    Noguchi, Shuji; Fujiki, Sadahiro; Iwao, Yasunori; Miura, Keiko; Itai, Shigeru

    2012-03-01

    In the crystal structure of the title compound, clarithromycin (CAM) monohydrate, C(38)H(69)NO(13)·H(2)O, the water mol-ecule behaves as a proton donor and is hydrogen bonded to the hy-droxy O atom of the CAM cladinose ring. The hy-droxy O atom also behaves as a proton donor, forming an inter-molecular hydrogen bond with one of the hy-droxy groups of the 14-membered aglycone ring. The CAM mol-ecules are linked through these hydrogen bonds into chains running parallel to the c axis.

  6. 3-[(E-(7-Chloro-4-quinolylhydrazonomethyl]benzonitrile monohydrate

    Directory of Open Access Journals (Sweden)

    Edward R. T. Tiekink

    2009-12-01

    Full Text Available The title monohydrate, C17H11ClN4·H2O, features an essentially planar organic molecule, as seen in the dihedral angle of 2.42 (8° formed between the quinoline and benzene planes. The conformation about the imine bond is E, and the N—H group is oriented towards the quinoline residue. The major feature of the crystal packing is the formation of supramolecular chains along [100], whereby the water molecule accepts one N—H...O hydrogen bond and makes two O—H...N hydrogen bonds. A C—H...O link is also present.

  7. Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation.

    Science.gov (United States)

    Kumar, Ashish; Alakarjula, Maija; Vanhoorne, Valérie; Toiviainen, Maunu; De Leersnyder, Fien; Vercruysse, Jurgen; Juuti, Mikko; Ketolainen, Jarkko; Vervaet, Chris; Remon, Jean Paul; Gernaey, Krist V; De Beer, Thomas; Nopens, Ingmar

    2016-07-30

    Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and kneading elements in the granulator screw allowing the production of granules with a size distribution appropriate for tableting. The distribution of residence time and granulation liquid is governed by the field conditions (such as location and length of mixing zones) in the twin-screw granulator, thus contain interesting information on granulation time, mixing and resulting sub-processes such as wetting, aggregation and breakage. In this study, the impact of process (feed rate, screw speed and liquid-to-solid ratio) and equipment parameters (number of kneading discs and stagger angle) on the residence time (distribution), the granulation liquid-powder mixing and the resulting granule size distributions during twin-screw granulation were investigated. Residence time and axial mixing data was extracted from tracer maps and the solid-liquid mixing was quantified from moisture maps, obtained by monitoring the granules at the granulator outlet using near infra-red chemical imaging (NIR-CI). The granule size distribution was measured using the sieving method. An increasing screw speed dominantly reduced the mean residence time. Interaction of material throughput with the screw speed and with the number of kneading discs led to most variation in the studied responses including residence time and mixing capacity. At a high screw speed, granulation yield improved due to high axial mixing. However, increasing material throughput quickly lowers the yield due to insufficient mixing of liquid and powder. Moreover, increasing liquid-to-solid ratio resulted in more oversized granules, and the fraction of oversized granules further increased at higher throughput. Although an increasing number

  8. Granulation techniques and technologies: recent progresses

    OpenAIRE

    Srinivasan Shanmugam

    2015-01-01

    Granulation, the process of particle enlargement by agglomeration technique, is one of the most significant unit operations in the production of pharmaceutical dosage forms, mostly tablets and capsules. Granulation process transforms fine powders into free-flowing, dust-free granules that are easy to compress. Nevertheless, granulation poses numerous challenges due to high quality requirement of the formed granules in terms of content uniformity and physicochemical proper...

  9. Granulopoiesis and granules of human neutrophils

    DEFF Research Database (Denmark)

    Cowland, Jack B; Borregaard, Niels

    2016-01-01

    Granules are essential for the ability of neutrophils to fulfill their role in innate immunity. Granule membranes contain proteins that react to environmental cues directing neutrophils to sites of infection and initiate generation of bactericidal oxygen species. Granules are densely packed...... with proteins that contribute to microbial killing when liberated to the phagosome or extracellularly. Granules are, however, highly heterogeneous and are traditionally subdivided into azurophil granules, specific granules, and gelatinase granules in addition to secretory vesicles. This review will address...... issues pertinent to formation of granules, which is a process intimately connected to maturation of neutrophils from their precursors in the bone marrow. We further discuss possible mechanisms by which decisions are made regarding sorting of proteins to constitutive secretion or storage in granules...

  10. The use of rheology to elucidate the granulation mechanisms of a miscible and immiscible system during continuous twin-screw melt granulation.

    Science.gov (United States)

    Monteyne, Tinne; Heeze, Liza; Mortier, Séverine Thérèse F C; Oldörp, Klaus; Nopens, Ingmar; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

    2016-08-20

    Twin-screw hot melt granulation (TS HMG) is a valuable, but still unexplored alternative to granulate temperature and moisture sensitive drugs in a continuous way. Recently, the material behavior of an immiscible drug-binder blend during TS HMG was unraveled by using a rheometer and differential scanning calorimetry (DSC). Additionally, vibrational spectroscopic techniques proved the link between TS HMG and rheology since equal interactions at molecular level did occur in both processes. This allowed to use a rheometer to gain knowledge of the material behavior during hot melt processing of an immiscible drug-binder blend. However, miscibility of a drug-binder formulation and drug-binder interactions appear to influence the rheological properties and, hence conceivably also the granulation mechanism. The aim of this research was to examine if the TS HMG process of a miscible formulation system is comparable with the mechanism of an immiscible system and to evaluate whether rheology still serves as a useful tool to understand and optimize the hot melt granulation (HMG) process. The executed research (thermal analysis, rheological parameters and spectroscopic data) demonstrated the occurrence of a high and broad tan(δ) curve without a loss peak during the rheological temperature ramp which implies a higher material deformability without movement of the softened single polymer chains. Spectroscopic analysis revealed drug-polymer interactions which constrain the polymer to flow independently. As a result, the binder distribution step, which generally follows the immersion step, was hindered. This insight assisted the understanding of the granule properties. Inhomogeneous granules were produced due to large initial nuclei or adhesion of multiple smaller nuclei. Consequently, a higher granulation temperature was required in order to get the binder more homogeneously distributed within the granules. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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

  12. Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation

    DEFF Research Database (Denmark)

    Kumar, Ashish; Alakarjula, Maija; Vanhoorne, Valérie

    2016-01-01

    Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and kneading...... elements in the granulator screw allowing the production of granules with a size distribution appropriate for tableting. The distribution of residence time and granulation liquid is governed by the field conditions (such as location and length of mixing zones) in the twin-screw granulator, thus contain...... interesting information on granulation time, mixing and resulting sub-processes such as wetting, aggregation and breakage. In this study, the impact of process (feed rate, screw speed and liquid-to-solid ratio) and equipment parameters (number of kneading discs and stagger angle) on the residence time...

  13. Influence of Differing Analgesic Formulations of Aspirin on Pharmacokinetic Parameters

    Directory of Open Access Journals (Sweden)

    Kunal Kanani

    2015-08-01

    Full Text Available Aspirin has been used therapeutically for over 100 years. As the originator and an important marketer of aspirin-containing products, Bayer’s clinical trial database contains numerous reports of the pharmacokinetics of various aspirin formulations. These include evaluations of plain tablets, effervescent tablets, granules, chewable tablets, and fast-release tablets. This publication seeks to expand upon the available pharmacokinetic information concerning aspirin formulations. In the pre-systemic circulation, acetylsalicylic acid (ASA is rapidly converted into its main active metabolite, salicylic acid (SA. Therefore, both substances are measured in plasma and reported in the results. The 500 mg strength of each formulation was chosen for analysis as this is the most commonly used for analgesia. A total of 22 studies were included in the analysis. All formulations of 500 mg aspirin result in comparable plasma exposure to ASA and SA as evidenced by AUC. Tablets and dry granules provide a consistently lower Cmax compared to effervescent, granules in suspension and fast release tablets. Effervescent tablets, fast release tablets, and granules in suspension provide a consistently lower median Tmax compared to dry granules and tablets for both ASA and SA. This report reinforces the importance of formulation differences and their impact on pharmacokinetic parameters.

  14. Perfluorobutyric Acid and its Monohydrate: a Chirped Pulse and Cavity Based Fourier Transform Microwave Spectroscopic Study

    Science.gov (United States)

    Thomas, Javix; Serrato, Agapito, III; Lin, Wei; Jaeger, Wolfgang; Xu, Yunjie

    2014-06-01

    Perfluorobutyric acid (PFBA) is highly soluble in water and is a molecule of environmental importance. Rotational spectra of PFBA and its monohydrate were studied using a broadband chirped pulse and a narrow band cavity based Fourier transform microwave spectrometers and high level ab initio calculations. Extensive conformational search was performed for both the acid and its monohydrate at the MP2/6-311++G(2d,p) level of theory. Two and three conformers were predicted for PFBA and its monohydrate, respectively. One set of rotational transitions of PFBA and its mono-hydrate in each case was observed and assigned. Based on the broadband spectra obtained, one can confidently conclude that only one dominate conformer exists in each case. The orientation of the hydroxyl group in PFBA was determined using isotopic analysis. Comparison of the observed transition intensities and the calculated electric dipole moment components allowed one to identify the most stable monohydrate conformation which takes on the insertion hydrogen-bonding topology. Comparison to the shorter chain analogues, i.e. trifluoroacetic acid, perfluoropropionic acid, and their monohydrates, was made to elucidate the general trend in their conformational preference and binding topologies.

  15. Perfluorobutyric acid and its monohydrate: a chirped pulse and cavity based fourier transform microwave spectroscopic study.

    Science.gov (United States)

    Thomas, Javix; Serrato, Agapito; Lin, Wei; Jäger, Wolfgang; Xu, Yunjie

    2014-05-12

    Rotational spectra of perfluorobutyric acid (PFBA) and its monohydrate were studied with a broadband chirped pulse and a narrow-band cavity based Fourier transform microwave spectrometer, and high-level ab initio calculations. Extensive conformational searches were performed for both the acid and its monohydrate at the MP2/6-311++G(2d,p) level of theory. Two and three conformers were predicted to exist for PFBA and its monohydrate, respectively. One set of rotational transitions was observed and assigned for each, PFBA and its monohydrate. Based on the measured broadband spectra, we confidently conclude that only one dominant conformer exists in each case. The orientation of the hydroxyl group in PFBA was determined by using isotopic analysis. Comparison of the observed transition intensities and the calculated electric dipole moment components allowed us to identify the most stable monohydrate conformation, which takes on an insertion hydrogen-bonding topology. Comparisons to the shorter chain analogues, that is, trifluoroacetic acid, perfluoropropionic acid, and their monohydrates, are made to elucidate the general trend in their conformational preference and binding topologies.

  16. Variation of granule mass fraction with coordination number in wet granulation process

    Institute of Scientific and Technical Information of China (English)

    Papiya Roy; Manish Vashishtha; Rajesh Khanna; Duwuri Subbarao

    2009-01-01

    In granulation, fine particles combine to form a coarse granule in the form of a particle matrix partially or fully saturated with a binder liquid. The final product of granulation possesses a wide variety of granule size distributions with surface mean diameters which differ with operating conditions. The final granule size depends on the operating conditions, e.g. operating gas velocity, inlet air temperature, initial feed particle size, and viscosity of the binder. The objective of this paper is to find out the uniformity in the relation between the granule mass fraction in the final granule size distribution and the number of feed particles present in the granules. The total number of granules obtained depends on the experimental conditions but the granule mass fraction and the number of feed particles forming a single granule are independent of operating variables, feed material and method of granulation. The paper purports further to compare the uniform nature of mass fraction of the granules in final granule size distribution and the primary particles required to form that particular granule size irrespective of experimental conditions of granulation.

  17. Calcium oxalate monohydrate precipitation investigation by thermometric method

    Science.gov (United States)

    Söhnel, O.; Costa-Bauzá, A.; Velich, V.

    1993-01-01

    Calcium oxalate monohydrate (COM) precipitation from diluted solutions of 100 mol m -3 ionic strength at 25°C was studied by an isoperibolic reaction twin calorimeter. The molar reaction enthalpy was determined as - 17.5 kJ mol -1. Results achieved with a pure system were highly reproducible. Citrate, pyrophosphate and phytate retard COM precipitation that is manifested mainly by an induction period appearance and a decrease of the initial precipitation rate. Effect of the studied impurities on individual precipitation experiments carried out under identical conditions was to some extent "random", i.e. the reaction extent reached at arbitrary time considerably differed for individual experiments. Impurity effectiveness in retarding spontaneous precipitation increases in succession citrate phytate.

  18. (S-2-Azaniumyl-2-methyl-3-phenylpropanoate monohydrate

    Directory of Open Access Journals (Sweden)

    Isao Fujii

    2016-10-01

    Full Text Available The title compound, C10H13NO2·H2O, crystallizes in a zwitterionic form as a monohydrate, involving the propylbenzene group with a trans conformation. It is a non-natural amino acid, and has attracted attention as an inhibitor of phenylalanine hydroxylase. In the crystal, molecules are linked by N—H...O hydrogen bonds, forming C(5 chains along the c-axis direction. Two chains are linked by another N—H...O hydrogen bond, forming an R33(11 ring motif. Further O—H...O hydrogen bonds link these motifs via the water molecules, to form a three-dimensional framework.

  19. Bioavailability of cefuroxime axetil formulations.

    Science.gov (United States)

    Donn, K H; James, N C; Powell, J R

    1994-06-01

    Cefuroxime axetil tablets have proved effective for the treatment of a variety of community-acquired infections. A suspension formulation has been developed for use in children. Two studies have been conducted to determine if the cefuroxime axetil formulations are bioequivalent. In the initial randomized, two-period crossover study, 24 healthy men received 250-mg doses of suspension and tablet formulations of cefuroxime axetil every 12 h after eating for seven doses. Each treatment period was separated by 4 days. Comparisons of serum and urine pharmacokinetic parameters indicated that the suspension and tablet formulations of cefuroxime axetil are not bioequivalent. Following the initial bioequivalency study, 0.1 % sodium lauryl sulfate (SLS) was added to the suspension to assure the homogeneity of the granules during the manufacturing process. In the subsequent randomized, three-period crossover study, 24 healthy men received single 250-mg doses of three cefuroxime axetil formulations: suspension without SLS, suspension with SLS, and tablet. Again each treatment period was separated by 4 days. Pharmacokinetic analyses demonstrated that while the suspension with SLS and suspension without SLS are bioequivalent, bioequivalence between the suspension with SLS and the tablet was not observed. Thus, the addition of the SLS surfactant to the suspension did not alter the bioavailability of the formulation.

  20. Application of spray granulation for conversion of a nanosuspension into a dry powder form.

    Science.gov (United States)

    Bose, Sonali; Schenck, Daniel; Ghosh, Indrajit; Hollywood, Al; Maulit, Ester; Ruegger, Colleen

    2012-08-30

    The in vivo effect of particle agglomeration after drying of nanoparticles has not been extensively studied till date based on current literature review. The purpose of this research was to evaluate the feasibility of spray granulation as a processing method to convert a nanosuspension of a poorly water soluble drug into a solid dosage form and to evaluate the effect of the transformation into a solid powder on the in vivo exposure in beagle dogs. Formulation variables like the level of stabilizer in the nanosuspension formulation, granulation substrate and drug loading in the granulation were evaluated. The granules were characterized for moisture content, drug content, particle size, crystallinity and in vitro dissolution rate. Granulations with 10% drug loading showed dissolution profiles comparable to the nanosuspension, slightly slower dissolution profiles were observed at 20% drug loading. This can be attributed to an increase in the surface hydrophobicity at a higher drug loading and the formation of agglomerates that were harder to disintegrate, thereby compromising the dissolution rate. An in vivo PK study in beagle dogs showed an 8-fold increase and a 6-fold increase in the AUC(0-48) from the nanosuspension and dried nanosuspension formulations respectively compared to the coarse suspension. Also, the nanosuspension and dried nanosuspension formulations showed a 12-fold and 8-fold increase in the C(max) respectively compared to the coarse suspension. This shows the feasibility of using spray granulation as a processing method to convert a nanosuspension into a solid dosage form with improved in vivo exposure compared to the coarse suspension formulation.

  1. Development and physical evaluation of Maytenus ilicifolia effervescent granules using factorial design

    Directory of Open Access Journals (Sweden)

    Marcilio Sérgio Soares da Cunha-Filho

    2014-04-01

    Full Text Available The medicinal plant Maytenus ilicifolia is a commonly used phytomedicine for the treatment of gastritis. The high dose required and low density of these extracts make necessary a daily intake of several capsules, hindering adherence to the medication. The purpose of this work was to develop a suitable dosage form for the administration of Maytenus ilicifolia using effervescent granules. A 23 factorial design was used to study the physical characteristics of the granules (particle size distribution, repose angle, Carr index, scanning electron microscopy and disintegration time. Moisture stability was also determined. According to the experimental design, granule size is the most important factor in determining the flow characteristics of effervescent granules. In turn, the disintegration time is controlled by the content of sodium bicarbonate present in the effervescent mixture as well as the granule size. The stability of formulations when exposed to moisture is strongly influenced by the percentage of effervescent mixture present in the vegetal granules. Precautions in handling and storage should be taken to ensure the stability of these preparations. The effervescent granules produced from Maytenus ilicifolia met the pharmacopoeial quality parameters, with appropriate mechanical and physical characteristics and proved to be a promising vehicle for plant extracts.

  2. A Novel Method Isolated Microorganisms in Soil Granule

    Institute of Scientific and Technical Information of China (English)

    Liu Bao-ping; Xiang Wen-sheng; Wang Hong-yan; Fu Shi-cong

    2012-01-01

    A novel method isolated microorganisms in soil granule was built. The key steps included: repeated elutriation of soil by sterilized water, inoculation on the plates with the elutriated sediments, incubation of the plates and isolation of the actinomycetes by using selected culture medium. We formulated that most microflora included the dominant actinomycetes in the soil were carried away with the sterilized water in the elutriation procedure, some rare actinomycetes and few other microflora included bacteria were remained in the elutriated sediments, the other microflora were excluded to grew into colonies on the plates by using selective culture medium for actinomycetes in the elutriated sediments. Results showed the supposition. Non-streptomycete actinomycetes were isolated both from black soil samples from Chinese northeast area and compost samples from Chinese central area. Soil fungi in granule were isolated by using the selective conditions to favor fungi. The results showed that the method was effective

  3. Excipient quantitation and drug distribution during formulation optimization.

    Science.gov (United States)

    Forget, Robert; Spagnoli, Suzanne

    2006-06-07

    An oral granules formulation experienced high drug content and increased variability when the process was scaled up from lab scale to clinical manufacturing scale. It was suspected that mannitol, due to its smaller particle size and lower density, was preferentially lost during the top spray granulation process, thereby causing active enrichment in the remaining granules. In order to troubleshoot the problem, rapidly evaluate solutions, and further optimize the formulation, a simple and rapid analytical technique was required. Since mannitol does not have a UV chromophore, conventional HPLC/UV analysis could not be used. Three alternative analytical techniques were evaluated in terms of ease of use, reproducibility, linear dynamic range and rapidity. The HPLC/RID (refractive index detector) and HPLC/ELSD (evaporative light scattering detector) provided rapid, reproducible alternate techniques to HPLC/UV, whereas LC/MS showed poor reproducibility. Analysis of the sieve samples of the granulations by HPLC/RID and HPLC/ELSD confirmed that poor active drug distribution was due to mannitol losses in the filter bag, as well as increased low size granules low in active drug content. The resultant formulation process was modified and a reduction in the initial air flow at start-up reduced losses of mannitol in the granulator filters.

  4. Regulation of secretory granule size by the precise generation and fusion of unit granules.

    Science.gov (United States)

    Hammel, Ilan; Lagunoff, David; Galli, Stephen J

    2010-07-01

    Morphometric evidence derived from studies of mast cells, pancreatic acinar cells and other cell types supports a model in which the post-Golgi processes that generate mature secretory granules can be resolved into three steps: (1) fusion of small, Golgi-derived progranules to produce immature secretory granules which have a highly constrained volume; (2) transformation of such immature granules into mature secretory granules, a process often associated with a reduction in the maturing granule's volume, as well as changes in the appearance of its content and (3) fusion of secretory granules of the smallest size, termed 'unit granules', forming granules whose volumes are multiples of the unit granule's volume. Mutations which perturb this process can cause significant pathology. For example, Chediak-Higashi syndrome / lysosomal trafficking regulator (CHS)/(Lyst) mutations result in giant secretory granules in a number of cell types in human beings with the Chediak-Higashi syndrome and in 'beige' (Lyst(bg)/Lyst(bg)) mice. Analysis of the secretory granules of mast cells and pancreatic acinar cells in Lyst-deficient beige mice suggests that beige mouse secretory granules retain the ability to fuse randomly with other secretory granules no matter what the size of the fusion partners. By contrast, in normal mice, the pattern of granule-granule fusion occurs exclusively by the addition of unit granules, either to each other or to larger granules. The normal pattern of fusion is termed unit addition and the fusion evident in cells with CHS/Lyst mutations is called random addition. The proposed model of secretory granule formation has several implications. For example, in neurosecretory cells, the secretion of small amounts of cargo in granules constrained to a very narrow size increases the precision of the information conveyed by secretion. By contrast, in pancreatic acinar cells and mast cells, large granules composed of multiple unit granules permit the cells to store

  5. Selective sorting of alpha-granule proteins.

    Science.gov (United States)

    Italiano, J E; Battinelli, E M

    2009-07-01

    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. A majority of this vast array of secreted proteins are stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on the mechanisms of alpha-granule biogenesis and secretion, with a particular emphasis on recent findings that clearly demonstrate that platelets contain distinct subpopulations of alpha-granules that undergo differential release during activation. We consider the implications of this new paradigm of platelet secretion, discuss mechanisms of alpha-granule biogenesis, and review the molecular basis of transport and delivery of alpha-granules to assembling platelets.

  6. Formulation, Characterization and Physicochemical Evaluation of Potassium Citrate Effervescent Tablets

    Directory of Open Access Journals (Sweden)

    Fatemeh Fattahi

    2013-02-01

    Full Text Available Purpose: The aim of this study was to design and formulation of potassium citrate effervescent tablet for reduction of calcium oxalate and urate kidney stones in patients suffering from kidney stones. Methods: In this study, 13 formulations were prepared from potassium citrate and effervescent base in different concentration. The flowability of powders and granules was studied. Then effervescent tablets were prepared by direct compression, fusion and wet granulation methods. The prepared tablets were evaluated for hardness, friability, effervescent time, pH, content uniformity. To amend taste of formulations, different flavoring agents were used and then panel test was done by using Latin Square method by 30 volunteers. Results: Formulations obtained from direct compression and fusion methods had good flow but low hardness. Wet granulation improves flowability and other physicochemical properties such as acceptable hardness, effervescence time ≤3 minutes, pH<6, friability < 1%, water percentage < 0.5% and accurate content uniformity. In panel test, both of combination flavors; (orange - lemon and (strawberry - raspberry had good acceptability. Conclusion: The prepared tablets by wet granulation method using PVP solution had more tablet hardness. It is a reproducible process and suitable to produce granules that are compressed into effervescent tablets due to larger agglomerates.

  7. Continuous twin-screw granulation for enhancing the dissolution of poorly water soluble drug.

    Science.gov (United States)

    Maniruzzaman, Mohammed; Nair, Arun; Renault, Maxcene; Nandi, Uttom; Scoutaris, Nicholaos; Farnish, Richard; Bradley, Michael S A; Snowden, Martin J; Douroumis, Dennis

    2015-12-30

    The article describes the application of a twin-screw granulation process to enhance the dissolution rate of the poorly water soluble drug, ibuprofen (IBU). A quality-by-design (QbD) approach was used to manufacture IBU loaded granules via hot-melt extrusion (HME) processing. For the purpose of the study, a design of experiment (DoE) was implemented to assess the effect of the formulation compositions and the processing parameters. This novel approach allowed the use of, polymer/inorganic excipients such as hydroxypropyl methylcellulose (HPMC) and magnesium aluminometasilicate (Neusilin(®)-MAS) with polyethylene glycol 2000 (PEG) as the binder without requiring a further drying step. IBU loaded batches were processed using a twin screw extruder to investigate the effect of MAS/polymer ratio, PEG amount (binder) and liquid to solid (L/S) ratios on the dissolution rates, mean particle size and the loss on drying (LoD) of the extruded granules. The DoE analysis showed that the defined independent variables of the twin screw granulation process have a complex effect on the measured outcomes. The solid state analysis showed the existence of partially amorphous IBU state which had a significant effect on the dissolution enhancement in acidic media. Furthermore, the analysis obtained from the surface mapping by Raman proved the homogenous distribution of the IBU in the extruded granulation formulations.

  8. Terahertz spectra of l-phenylalanine and its monohydrate.

    Science.gov (United States)

    Pan, Tingting; Li, Shaoping; Zou, Tao; Yu, Zheng; Zhang, Bo; Wang, Chenyang; Zhang, Jianbing; He, Mingxia; Zhao, Hongwei

    2017-05-05

    The low-frequency vibrational property of l-phenylalanine (l-Phe) and l-phenylalanine monohydrate (l-Phe·H2O) has been investigated by terahertz time-domain spectroscopy (THz-TDS) at room and low temperature ranging from 0.5 to 4.5THz. Distinctive THz absorption spectra of the two compounds were observed. Density functional theory (DFT) calculations based on the crystal structures have been performed to simulate the vibrational modes of l-Phe and l-Phe·H2O and the results agree well with the experimental observations. The study indicates that the characterized features of l-Phe mainly originate from the collective vibration of molecules. And the characterized features of l-Phe·H2O mainly come from hydrogen bond interactions between l-Phe and water molecules. l-Phe and l-Phe·H2O were also verified by differential scanning calorimetry and thermogravimetry (DSC-TG) and powder X-ray diffraction (PXRD) examinations. Copyright © 2017. Published by Elsevier B.V.

  9. Thermochemical Properties and Decomposition Kinetics of Ammonium Magnesium Phosphate Monohydrate

    Institute of Scientific and Technical Information of China (English)

    WU,Jian; YUAN,Ai-Qun; HUANG,Zai-Yin; TONG,Zhang-Fa; CHEN,Jie; LIANG,Rong-Lan

    2007-01-01

    Ammonium magnesium phosphate monohydrate NH4MgPO4·H2O was prepared via solid state reaction at room temperature and characterized by XRD, FT-IR and SEM. Thermochemical study was performed by an isoperibol solution calorimeter, non-isothermal measurement was used in a multivariate non-linear regression analysis to determine the kinetic reaction parameters. The results show that the molar enthalpy of reaction above is (28.795±0.182) kJ/mol (298.15 K), and the standard molar enthalpy of formation of the title complex is (-2185.43±13.80)kJ/mol (298.15 K). Kinetics analysis shows that the second decomposition of NH4MgPO4·H2O acts as a double-step reaction: an nth-order reaction (Fn) with n=4.28, E1=147.35 kJ/mol, A1=3.63×1013 s-1 is followed by a second-order reaction (F2) with E2=212.71 kJ/mol, A2= 1.82×1018 s-1.

  10. Synthesis, properties and supramolecular structure of piperazinediium thiosulfate monohydrate

    Indian Academy of Sciences (India)

    Bikshandarkoil R Srinivasan; Ashish R Naik; Sunder N Dhuri; Christian Näther; Wolfgang Bensch

    2011-01-01

    Aqueous reaction of ammonium thiosulfate with piperazine (pip) results in the formation of the title compound (pipH2)[S2O3]$\\cdot$H2O 1 (pipH2 = piperazinediium) in good yield. 1 was characterized by elemental analysis, IR, Raman andNMRspectra, X-ray powder pattern and its structure was determined. On heating at 100°C, 1 transforms to anhydrous piperazinediium thiosulfate 2, which can be rehydrated to the monohydrate on exposure tomoisture. The structure of 1 consists of two crystallographically independent piperazinediium (pipH2)2+ cations located on inversion centers, a thiosulfate anion and a lattice water. The organic cations, thiosulfate anion and lattice water are linked by six varieties of hydrogen bond namely O-H$\\cdots$O, O-H$\\cdots$S, N-H$\\cdots$O, N-H$\\cdots$S, C-H$\\cdots$O and C-H$\\cdots$S, leading to the formation of alternating layers of (pipH2)2+ cations and water linked thiosulfate chains. A comparative study of several compounds charge balanced by the piperazinediium cation is described.

  11. Continuous twin screw melt granulation of glyceryl behenate: Development of controlled release tramadol hydrochloride tablets for improved safety.

    Science.gov (United States)

    Keen, Justin M; Foley, Connor J; Hughey, Justin R; Bennett, Ryan C; Jannin, Vincent; Rosiaux, Yvonne; Marchaud, Delphine; McGinity, James W

    2015-06-20

    Interest in granulation processes using twin screw extrusion machines is rapidly growing. The primary objectives of this study were to develop a continuous granulation process for direct production of granules using this technique with glyceryl behenate as a binder, evaluate the properties of the resulting granules and develop controlled release tablets containing tramadol HCl. In addition, the granulation mechanism was probed and the polymorphic form of the lipid and drug release rate were evaluated on stability. Granules were prepared using a Leistritz NANO16 twin screw extruder operated without a constricting die. The solid state of the granules were characterized by differential scanning calorimetry and X-ray diffraction. Formulated tablets were studied in 0.1N HCl containing 0-40% ethanol to investigate propensity for alcohol induced dose dumping. The extrusion barrel temperature profile and feed rate were determined to be the primary factors influencing the particle size distribution. Granules were formed by a combination immersion/distribution mechanism, did not require subsequent milling, and were observed to contain desirable polymorphic forms of glyceryl behenate. Drug release from tablets was complete and controlled over 16 h and the tablets were determined to be resistant to alcohol induced dose dumping. The drug release rate from the tablets was found to be stable at 40°C and 75% relative humidity for the duration of a 3 month study.

  12. Selective sorting of alpha-granule proteins

    OpenAIRE

    Italiano, J.E.; Battinelli, E. M.

    2009-01-01

    One of the main functions of blood platelets is to secrete a variety of substances that can modify a developing thrombus, regulate the growth of the vasculature, promote wound repair, and contribute to cell-adhesive events. The majority of this vast array of secreted proteins is stored in alpha-granules. Until recently, it was assumed that platelets contained one homogeneous population of alpha-granules that undergo complete de-granulation during platelet activation. This review focuses on th...

  13. The extrusion properties of potato granules

    OpenAIRE

    Kooi, Eng Teong

    1982-01-01

    Potato granules from different sources were found, on extrusion, to produce potato snacks of variable quality. In some instances strip formation was unsatisfactory, in other instances blistering of the snack occurred on frying. In total, about 20-25 batches of potato granules were examined and classified in relation to these two phenomena. The amylose/amylopectin ratios of these samples of potato granules were determined by the semi-micro potentiometric iodine titration technique, but it was ...

  14. The effects of the recommended dose of creatine monohydrate on kidney function.

    Science.gov (United States)

    Taner, Basturk; Aysim, Ozagari; Abdulkadir, Unsal

    2011-02-01

    We report a case of a heretofore healthy 18-year-old man who presented with a 2-day history of nausea, vomiting and stomach ache while taking creatine monohydrate for bodybuilding purposes. The patient had acute renal failure, and a renal biopsy was performed to determine the cause of increased creatinine and proteinuria. The biopsy showed acute tubular necrosis. In the literature, creatine monohydrate supplementation and acute tubular necrosis coexistence had not been reported previously. Twenty-five days after stopping the creatine supplements, the patient recovered fully. Even recommended doses of creatine monohydrate supplementation may cause kidney damage; therefore, anybody using this supplement should be warned about this possible side effect, and their renal functions should be monitored regularly.

  15. Medical image of the week: granulation tissue

    Directory of Open Access Journals (Sweden)

    Ganesh A

    2014-03-01

    Full Text Available A 57 year old woman presented with a tickling sensation in the back of throat and intermittent bleeding from the healing stoma one month after decannulation of her tracheostomy tube. On bronchoscopy a granuloma with surrounding granulation tissue was present in the subglottic space (Figure 1. Argon plasma coagulation (APC was performed to cauterize the granulation tissue (Figure 2. Formation of granulation tissue after tracheostomy is a common complication which can result in tracheal stenosis. APC and electrocautery using flexible bronchoscopy has been shown to safely and effectively remove the granulation tissue.

  16. Mechanism of film formation during granules capsulation in fluidized bed

    OpenAIRE

    Ostroha, Ruslan; Yukhymenko, Mykola

    2013-01-01

    It is proposed to perform granules capsulation process in the device of fluidized bed. Analysis of different approaches to mathematical description of granules growth kinetics was made. Equation of size determination of received granules in the device is proposed including granules growth rate and changes of density of granules distribution according to sizes in film forming process.

  17. Granulation of coal fly ash by using different types of granule agents

    Science.gov (United States)

    Agusta, H.; Nisya, F. N.; Iman, R. N.; Bilad, D. B. C.

    2017-05-01

    The use of coal produces about 5% solid pollutant in the form of ash (fly ash and bottom ash). Of the total ash produced, about 10-20% is bottom ash and 80-90% is fly ash. This study was aimed at obtaining a type of adhesive which could be used as a fly granulation material for soil conditioner. The study was conducted at the pilot plant of Surfactant and Bioenergy Research Center (SBRC) LPPM IPB from April to August 2016. The fly ash used in this study was obtained from Kalimantan. A pan granulator was used in fly ash granule making process. Granule agent materials were diluted in the concentration of 5, 10, and 15%. Different types of granule agents, namely SBRC-M, SBRC-T, and SBRC-SC were used. The formed fly ash granules were then analyzed for their physical properties including particle density, fly ash granule pH, fly ash granule durability, and fly ash granule water holding capacity. Results showed that fly ash granules made from 15% of SBRC-M had the highest particle density (0.75 g/cm3). Fly ash granules made with SBRC-M had higher pH (10) than those made by using SBRC-SC adhesive (9.3) and SBRC-T (9). SBRC-T was found as the granule agent material which produced fly ash granules with the highest durability levels on average. In this study, the use of SBRC-M granule agent resulted in higher water holding capacity (WHC) (40.62%) than did SBRC-SC (38.79%) and SBRC-T (36.85%). As a granule agent, compared to SBRC-SC and SBRC-T, SBRC-M could produce fly ash granules with highest particle density, highest pH, good durability, and best water holding capacity.

  18. Granule exocytosis is required for platelet spreading: differential sorting of α-granules expressing VAMP-7.

    Science.gov (United States)

    Peters, Christian G; Michelson, Alan D; Flaumenhaft, Robert

    2012-07-01

    There has been recent controversy as to whether platelet α-granules represent a single granule population or are composed of different subpopulations that serve discrete functions. To address this question, we evaluated the localization of vesicle-associated membrane proteins (VAMPs) in spread platelets to determine whether platelets actively sort a specific subpopulation of α-granules to the periphery during spreading. Immunofluorescence microscopy demonstrated that granules expressing VAMP-3 and VAMP-8 localized to the central granulomere of spread platelets along with the granule cargos von Willebrand factor and serotonin. In contrast, α-granules expressing VAMP-7 translocated to the periphery of spread platelets along with the granule cargos TIMP2 and VEFG. Time-lapse microscopy demonstrated that α-granules expressing VAMP-7 actively moved from the granulomere to the periphery during spreading. Platelets from a patient with gray platelet syndrome lacked α-granules and demonstrated only minimal spreading. Similarly, spreading was impaired in platelets obtained from Unc13d(Jinx) mice, which are deficient in Munc13-4 and have an exocytosis defect. These studies identify a new α-granule subtype expressing VAMP-7 that moves to the periphery during spreading, supporting the premise that α-granules are heterogeneous and demonstrating that granule exocytosis is required for platelet spreading.

  19. The paradox of high shear granulation : the formation of non-homogeneous granules

    NARCIS (Netherlands)

    Dries, Kaspar van den

    2004-01-01

    Wet granulation is a process used for the particle size enlargement of primary powders. The mixing of a liquid with the powder glues the primary particles together, which results in the formation of the granules. The mixing action can be performed in many ways, like tumbling (drum granulation), flui

  20. Granule fraction inhomogeneity of calcium carbonate/sorbitol in roller compacted granules

    DEFF Research Database (Denmark)

    Bacher, Charlotte; Olsen, P.M.; Bertelsen, P.;

    2008-01-01

    The granule fraction inhomogeneity of roller compacted granules was examined on mixtures of three different morphologic forms of calcium carbonate and three particle sizes of sorbitol. The granule fraction inhomogeneity was determined by the distribution of the calcium carbonate in each of the 10...

  1. Formas de adição de zinco a um formulado NPK e seu efeito sobre a produção de milho Zn rates and sources, added to a NPK granule formulation, and their effect on corn production

    Directory of Open Access Journals (Sweden)

    G.H. Korndörfer

    1995-12-01

    Full Text Available O presente trabalho teve como objetivo avaliar os efeitos de fontes, doses e formas de adição de zinco a um formulado NPK sobre a produção de grãos e matéria seca de milho em um solo de cerrado da região de Uberlândia, MG. Quatro doses de zinco foram aplicadas ao solo (0, 1, 2 e 4 kg de Zn ha-1, através de três formas (ZnO-incorporado, FTE BR-12-incorporado e FTE BR-12-gramilado adicionadas a um formulado NPK (4-30-10. O ZnO e as Fritas em pó foram incorporados ao formulado durante a fabricação, antes da granulação. Um tratamento adicional de FTE previamente granulado e depois misturado ao formulado, também foi testado. Os resultados mostraram que o zinco agregado ao adubo NPK não teve efeito sobre a produção de grãos de milho, nem tampouco sobre a produção de matéria seca, independentemente da dose ou da fonte empregada. Os teores de Zn na folha do milho aumentaram significativamente com as doses de Zn aplicada, sendo o ZnO incorporado ao granulo do formulado NPK, o tratamento que apresentou os mais altos teores. Por sua vez, o FTE em pó incorporado no granulo do formulado e o FTE previamente granulado e posteriormente misturado ao formulado não diferiram entre si quanto aos teores de Zn na folha.Zinc rates and sources added to a NPK granulated fertilizer was observed on corn crop cultivated on a soil originally under "cerrado" vegetation from Uberlândia, MG region. Four zinc rates (0, 1 , 2 e 4 kg ha-1 derived from three types of zinc sources (ZnO-incorporated, FTE BR-12-incorporated and granule FTE BR-12 were used. The ZnO and the "Fritted Trace Elements" (FTE BR-12 were incorporated to the fertilizer before granulation. An additional treatment with granule FTE and later blended to the NPK fertilizer was also tested. The results showed that Zn incorporated to the NPK fertilizer did not increase grain yield and dry matter yield. Zinc in the leaf tissue increased with the applied Zn rates, and the ZnO incorporated into

  2. Regulated protein aggregation: stress granules and neurodegeneration

    Directory of Open Access Journals (Sweden)

    Wolozin Benjamin

    2012-11-01

    Full Text Available Abstract The protein aggregation that occurs in neurodegenerative diseases is classically thought to occur as an undesirable, nonfunctional byproduct of protein misfolding. This model contrasts with the biology of RNA binding proteins, many of which are linked to neurodegenerative diseases. RNA binding proteins use protein aggregation as part of a normal regulated, physiological mechanism controlling protein synthesis. The process of regulated protein aggregation is most evident in formation of stress granules. Stress granules assemble when RNA binding proteins aggregate through their glycine rich domains. Stress granules function to sequester, silence and/or degrade RNA transcripts as part of a mechanism that adapts patterns of local RNA translation to facilitate the stress response. Aggregation of RNA binding proteins is reversible and is tightly regulated through pathways, such as phosphorylation of elongation initiation factor 2α. Microtubule associated protein tau also appears to regulate stress granule formation. Conversely, stress granule formation stimulates pathological changes associated with tau. In this review, I propose that the aggregation of many pathological, intracellular proteins, including TDP-43, FUS or tau, proceeds through the stress granule pathway. Mutations in genes coding for stress granule associated proteins or prolonged physiological stress, lead to enhanced stress granule formation, which accelerates the pathophysiology of protein aggregation in neurodegenerative diseases. Over-active stress granule formation could act to sequester functional RNA binding proteins and/or interfere with mRNA transport and translation, each of which might potentiate neurodegeneration. The reversibility of the stress granule pathway also offers novel opportunities to stimulate endogenous biochemical pathways to disaggregate these pathological stress granules, and perhaps delay the progression of disease.

  3. Preparation and Evaluation of Solid Dispersion Tablets by a Simple and Manufacturable Wet Granulation Method Using Porous Calcium Silicate.

    Science.gov (United States)

    Fujimoto, Yumi; Hirai, Nobuaki; Takatani-Nakase, Tomoka; Takahashi, Koichi

    2016-01-01

    The aim of this study was to prepare and evaluate solid dispersion tablets containing a poorly water-soluble drug using porous calcium silicate (PCS) by a wet granulation method. Nifedipine (NIF) was used as the model poorly water-soluble drug. Solid dispersion tablets were prepared with the wet granulation method using ethanol and water by a high-speed mixer granulator. The binder and disintegrant were selected from 7 and 4 candidates, respectively. The dissolution test was conducted using the JP 16 paddle method. The oral absorption of NIF was studied in fasted rats. Xylitol and crospovidone were selected as the binder and disintegrant, respectively. The dissolution rates of NIF from solid dispersion formulations were markedly enhanced compared with NIF powder and physical mixtures. Powder X-ray diffraction (PXRD) confirmed the reduced crystallinity of NIF in the solid dispersion formulations. Fourier transform infrared (FT-IR) showed the physical interaction between NIF and PCS in the solid dispersion formulations. NIF is present in an amorphous state in granules prepared by the wet granulation method using water. The area under the plasma concentration-time curve (AUC) and peak concentration (C(max)) values of NIF after dosing rats with the solid dispersion granules were significantly greater than those after dosing with NIF powder. The solid dispersion formulations of NIF prepared with PCS using the wet granulation method exhibited accelerated dissolution rates and superior oral bioavailability. This method is very simple, and may be applicable to the development of other poorly water-soluble drugs.

  4. Redetermination and absolute configuration of pruniflorone M monohydrate

    Directory of Open Access Journals (Sweden)

    Hoong-Kun Fun

    2011-08-01

    Full Text Available The title xanthone known as pruniflorone M (systematic name: (2R-5,10-dihydroxy-2-hydroxymethyl-1,1-dimethyl-1H-furo[2,3-c]xanthen-6-one, crystallized in a monohydrate form, C18H16O6·H2O. It was isolated from the green fruits of Cratoxylum formosum ssp. pruniflorum. The structure of the title compound has been reported previously [Boonnak et al. (2010. Aust. J. Chem. 63, 1550–1556], but we report here the absolute configuration determined using Cu Kα radiation. There are two crystallograpically independent molecules in the asymmetric unit, which differ slightly in the bond angles. The hydroxymethyl substituents at position 2 of the furan rings of both pruniflorone M molecules adopt R configurations. In both molecules, the three rings of the xanthone skeleton are approximately coplanar, with an r.m.s. deviation of 0.0124 (2 Å for one molecule and 0.0289 (2 Å for the other, and the furan ring adopts an envelope conformation. In the crystal, molecules of pruniflorone M and water are linked into a two-dimensional network by O—H...O hydrogen bonds and weak C—H...O interactions. The crystal structure is further consolidated by π–π interactions with centroid–centroid distances in the range 3.5987 (13–3.7498 (14 Å. Short C...C [3.378 (3 Å] and O...O [2.918 (3 Å] contacts are also observed.

  5. Origin and types of calcium oxalate monohydrate papillary renal calculi.

    Science.gov (United States)

    Grases, Fèlix; Costa-Bauzá, Antonia; Gomila, Isabel; Conte, Antonio

    2010-12-01

    Subepithelial hydroxyapatite calcification of renal papilla is thought to be involved in the formation of calcium oxalate monohydrate (COM) papillary calculi. To assess the mechanism of formation, we sought to correlate the fine structure of papillary renal calculi with specific pathophysiologic conditions and urinary alterations. The study included 831 COM papillary renal calculi with established fine inner structures. A total of 24 patients with chronic stone formation were randomly selected, and their urine was collected and analyzed. The case history and lifestyle habits of these patients were obtained. The 831 papillary calculi could be classified into 1 of 4 main groups. Type I included small calculi in which COM columnar crystals begin to develop in the concave zone in close contact with papillary tissue. Type II calculi contained a hydroxyapatite core located in or near the concave zone. Type III consisted of calculi that developed on the tip of the papillae and in the concave zone, containing hydroxyapatite, calcified tissue, and calcified tubules. Type IV consisted of papillary calculi in which the core, which is situated near, but not in, the concave zone, is formed by intergrown COM crystals and organic matter. Many factors, including urinary alterations (eg, hyperoxaluria), associated diseases (eg, hypertension, diabetes), and consumption or exposure to cytotoxic substances (eg, analgesic abuse) were associated with these types of calculi. Our findings have indicated that injury is the first cause of papillary COM calculus formation, with the location of the injury determining the morphology of the resulting calculus. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Magnesium and occluded water in calcium carbonate monohydrate

    Science.gov (United States)

    Dejehet, F.; Idrissi, S.; Debuys, R.

    1999-04-01

    Calcium carbonate monohydrate spherulites (˜102 μm diameter) with different magnesium contents were synthesized from artificial seawater. Stable spherulites are only obtained if [Mg]/[Ca] ≥ 1-1.3 in the mother solution. Spherulites are surrounded by a skin of ˜15 μm thickness, about 5 times richer in Mg2+ than the bulk and which play a protective role from the stability viewpoint. Etching and crushing experiments were performed which confirm i.a. that the isotropic CO3- and CO2- radicals are located in the occluded water surrounding the constituent crystallites of the spherulites. Des sphérules de carbonate de calcium monohydraté de ˜102 μm de diamètre avec des teneurs en magnésium différentes ont été synthétisées à partir d'eau de mer artificielle. Des sphérules stables ne sont obtenues que si [Mg]/[Ca] ≥ 1-1.3 dans la solution mère. Les sphérules sont entourées d'une peau de ˜15 μm d'épaisseur, à peu près 5 fois plus riche en Mg2+ que la masse et qui assure sa stabilité. Des expériences de décapage et de broyage ont confirmé e.a. que les radicaux isotropes CO3- et CO2- sont localisés dans l'eau occluse entourant les cristallites à l'intérieur des sphérules.

  7. Twin screw wet granulation: Binder delivery.

    Science.gov (United States)

    Saleh, Mohammed F; Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2015-06-20

    The effects of three ways of binder delivery into the twin screw granulator (TSG) on the residence time, torque, properties of granules (size, shape, strength) and binder distribution were studied. The binder distribution was visualised through the transparent barrel using high speed imaging as well as quantified using offline technique. Furthermore, the effect of binder delivery and the change of screw configuration (conveying elements only and conveying elements with kneading elements) on the surface velocity of granules across the screw channel were investigated using particle image velocimetry (PIV). The binder was delivered in three ways; all solid binder incorporated with powder mixture, 50% of solid binder mixed with powder mixture and 50% mixed with water, all the solid binder dissolved in water. Incorporation of all solid binder with powder mixture resulted in the relatively longer residence time and higher torque, narrower granule size distribution, more spherical granules, weaker big-sized granules, stronger small-sized granules and better binder distribution compared to that in other two ways. The surface velocity of granules showed variation from one screw to another as a result of uneven liquid distribution as well as shown a reduction while introducing the kneading elements into the screw configuration.

  8. Autophagy meets FUS-positive Stress Granules

    Science.gov (United States)

    Matus, Soledad; Bosco, Daryl A.; Hetz, Claudio

    2015-01-01

    Mutations in fused in sarcoma/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 and coworkers 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. PMID:25444610

  9. Development of granules from phyllanthus niruri spray-dried extract

    OpenAIRE

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

    2009-01-01

    The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility i...

  10. Examining drug hydrophobicity in continuous wet granulation within a twin screw extruder.

    Science.gov (United States)

    Li, H; Thompson, M R; O'Donnell, K P

    2015-12-30

    The influence of active pharmaceutical ingredient (API) hydrophobicity on continuous wet granulation was studied in twin screw granulation utilizing foamed binder delivery. The APIs examined were caffeine, acetaminophen, ibuprofen and griseofulvin and the drug load was maintained constant at 15 wt%. In order to understand the impact of these APIs on the granulation process, API and binder distribution, particle size, porosity, and fracture strength were analyzed on samples collected along the screw length. It was found that the API and binder distributions were uniform along the screws regardless of the hydrophobicity of the formulation, in contrast to literature results with liquid injection. The absence of de-mixing of the hydrophobic ingredient was hypothesized to be a result of the high spread-to-soak ratio of a foamed binder that 'cages' those particles within the mass of local hydrophilic solids.

  11. Influence of solvents on the habit modification of alpha lactose monohydrate single crystals

    Science.gov (United States)

    Parimaladevi, P.; Srinivasan, K.

    2013-02-01

    Restricted evaporation of solvent method was adopted for the growth of alpha lactose monohydrate single crystals from different solvents. The crystal habits of grown crystals were analysed. The form of crystallization was confirmed by powder x-ray diffraction analysis. Thermal behaviour of the grown crystals was studied by using differential scanning calorimetry.

  12. THE STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT WAYS OF GRANULATION

    Directory of Open Access Journals (Sweden)

    Rybachuk VD

    2016-12-01

    Full Text Available Introduction. Active substances and excipients used in the manufacture of medicines in tablet form, in most cases, have poor technological properties. This fact determines the need for prior granulation of mass before compression. Granulators of various sizes and designs, running on different modes, made the formation, growth and consolidation of the powder particles that lead to obtain pellets of different shapes and sizes. From the literature it is known that granulation leads to two forms of granules: isodiametric and nonisodiametric. The first group of particles forms has globular shape with a smooth surface and the proportion in which the length, thickness and height are about the same. They are usually made by fluidized bed granulation, spray drying, pelletizing and granulation in dragee pan. Granules of nonisodiametric form in which length is several times the width and height are made mostly by extrusion and compacting. The geometrical parameters of obtained granules are affected by the properties of raw materials, the granulation modes, type and amount of added humidifier and so on. The shape and size of granules, from a technological point of view, are the key factors that contribute, except organoleptic characteristics of the product, its technological properties such as particle size distribution, bulk volume, the ability of the material to shrinkage, porosity, fluidity, mechanical strength and so on. Properly selected for specific conditions granulation method is able to provide the finished product with the specified technological parameters depending on the needs. The aim of this work was to study the effect of granulation method and its conditions on the kinetics of growth of the natural zeolite granules and some quality characteristics of obtained granules. Material & methods. As objects of study served the natural zeolite pellets produced using 3%, 5%, 7% and 10% potato starch paste and solution of polyvinylpyrrolidone (PVP

  13. Correlative microscopy of detergent granules.

    Science.gov (United States)

    van Dalen, G; Nootenboom, P; Heussen, P C M

    2011-03-01

    The microstructure of detergent products for textile cleaning determines to a large extent the physical properties of these products. Correlative microscopy was used to reveal the microstructure by reconciling images obtained by scanning electron microscopy with energy dispersive X-ray analysis, X-ray microtomography and Fourier transform infrared microscopy. These techniques were applied on the same location of a subsample of a spray-dried detergent base powder embedded in polyacrylate. In this way, the three-dimensional internal and external structure of detergent granules could be investigated from milli to nano scale with detailed spatial information about the components present. This will generate knowledge how to design optimal microstructures for laundry products to obtain product properties demanded by the market. This method is also very useful for other powder systems used in a large variety of industries (e.g. for pharmaceutical, food, ceramic and metal industries).

  14. Formulation and Dissolution Study of Valsartan Immediate Release Tablets

    Directory of Open Access Journals (Sweden)

    B. Brahmaiah*, K. Sasikanth, Sreekanth Nama , P.Suresh, Patan Adam Khan

    2013-06-01

    Full Text Available In the present study, design of oral immediate release tablets of Valsartan by direct compression techniquewas carried out. The main aim and objective of the work is to formulate immediate release tablets usingdifferent direct compression vehicles (DCV’S in different ratios. The main motive is to compare thedissolution profile of these formulations and conclude the best formulation which release drug at a fasterrate. To determine the best fit dissolution profile for the dosage forms. Valsartan tablets were formulated byusing microcrystalline cellulose (diluents, potato starch, acacia (binder and magnesium stearate(lubricant. The granules were compressed into tablets and were subjected to dissolution studies. Thedissolution profile of the formulation F2 was found to have better dissolution rate compared to others. TheIn-vitro dissolution studies of all the formulations were conducted and the results were obtained, it wasconcluded that formulation F2 was the best with fast release of drug compared to others.

  15. Asymmetric distribution in twin screw granulation.

    Science.gov (United States)

    Chan Seem, Tim; Rowson, Neil A; Gabbott, Ian; de Matas, Marcel; Reynolds, Gavin K; Ingram, Andy

    2016-09-01

    Positron Emission Particle Tracking (PEPT) was successfully employed to validate measured transverse asymmetry in material distribution in the conveying zones of a Twin Screw Granulator (TSG). Flow asymmetry was established to be a property of the granulator geometry and dependent on fill level. The liquid distribution of granules as a function of fill level was determined. High flow asymmetry at low fill level negatively affects granule nucleation leading to high variance in final uniformity. Wetting of material during nucleation was identified as a critical parameter in determining final granule uniformity and fill level is highlighted as a crucial control factor in achieving this. Flow asymmetry of dry material in conveying zones upstream of binder fluid injection leads to poor non-uniform wetting at nucleation and results in heterogeneous final product. The granule formation mechanism of 60°F kneading blocks is suggested to be primarily breakage of agglomerates formed during nucleation. Optimisation of screw configuration would be required to provide secondary growth. This work shows how fill dependent flow regimes affect granulation mechanisms.

  16. Dry powder aerosols generated by standardized entrainment tubes from drug blends with lactose monohydrate: 1. Albuterol sulfate and disodium cromoglycate.

    Science.gov (United States)

    Xu, Zhen; Mansour, Heidi M; Mulder, Tako; McLean, Richard; Langridge, John; Hickey, Anthony J

    2010-08-01

    The major objective of this study was: discriminatory assessment of dry powder aerosol performance using standardized entrainment tubes (SETs) and lactose-based formulations with two model drugs. Drug/lactose interactive physical mixtures (2%w/w) were prepared. Their properties were measured: solid-state characterization of phase behavior and molecular interactions by differential scanning calorimetry and X-ray powder diffraction; particle morphology and size by scanning electron microscopy and laser diffraction; aerosol generation by SETs and characterization by twin-stage liquid impinger and Andersen cascade impactor operated at 60 L/min. The fine particle fraction (FPF) was correlated with SET shear stress (tau(s)), using a novel powder aerosol deaggregation equation (PADE). Drug particles were <5 microm in volume diameter with narrow unimodal distribution (Span <1). The lowest shear SET (tau(s) = 0.624 N/m(2)) gave a higher emitted dose (ED approximately 84-93%) and lower FPF (FPF(6.4) approximately 7-25%). In contrast, the highest shear SET (tau(s) = 13.143 N/m(2)) gave a lower ED (ED approximately 75-89%) and higher FPF (FPF(6.4) approximately 15-46%). The performance of disodium cromoglycate was superior to albuterol sulfate at given tau(s), as was milled with respect to sieved lactose monohydrate. Excellent correlation was observed (R(2) approximately 0.9804-0.9998) when pulmonary drug particle release from the surface of lactose carriers was interpreted by PADE linear regression for dry powder formulation evaluation and performance prediction.

  17. Improving the granule strength of roller-compacted ibuprofen sodium for hot-melt coating processing.

    Science.gov (United States)

    Lopes, Diogo Gomes; Garsuch, Verena; Becker, Karin; Paudel, Amrit; Stehr, Michael; Zimmer, Andreas; Salar-Behzadi, Sharareh

    2016-08-20

    Solvent-free hot-melt coating processing is a novel and cost-efficient approach to manufacturing taste-masked multiparticulate systems. However, most API powders are fine and cohesive and not processable by hot-melt coating. The aim of this study was to produce dense and abrasion-resistant granules with high drug content (>80%) via roller compaction for hot-melt coating process optimization. The selected API was ibuprofen sodium dihydrate, a salt of ibuprofen with improved bioavailability and poor intrinsic compactibility. The formulation and roller compaction process were developed for the production of granules with 94%w/w of API and low friability (∼30%), using sorbitol and isomalt as excipients. The strong bonding mechanism relied on powder jamming prior to the rollers and was investigated via scanning electron microscopy, differential scanning calorimetry and small and wide angle X-ray scattering. It was shown that sorbitol crystals are solubilized during roller compaction and recrystallize as sorbitol hydrate, acting as strong solid bridges. The robustness of the roller compaction process and the re-compaction of fines were investigated. A statistical design of experiments was conducted to evaluate the hot-melt coating process for taste masking of ibuprofen sodium granules. Taste masking required coating ratios higher than 40%w/w of granule batch, emphasizing the need for high-drug-content and abrasion-resistant granules.

  18. Modeling controlled nutrient release from polymer coated fertilizers: diffusion release from single granules.

    Science.gov (United States)

    Shaviv, Avi; Raban, Smadar; Zaidel, Elina

    2003-05-15

    A comprehensive model describing the complex and "non-Fickian" (mathematically nonlinear) nature of the release from single granules of membrane coated, controlled release fertilizers (CRFs) is proposed consisting of three stages: i. a lag period during which water penetrates the coating of the granule dissolving part of the solid fertilizer in it ii. a period of linear release during which water penetration into and release out occur concomitantly while the total volume of the granules remains practically constant; and iii. a period of "decaying release", starting as the concentration inside the granule starts to decrease. A mathematical model was developed based on vapor and nutrient diffusion equations. The model predicts the release stages in terms of measurable geometrical and chemophysical parameters such as the following: the product of granule radius and coating thickness, water and solute permeability, saturation concentration of the fertilizer, and its density. The model successfully predicts the complex and "sigmoidal" pattern of release that is essential for matching plant temporal demand to ensure high agronomic and environmental effectiveness. It also lends itself to more complex statistical formulations which account for the large variability within large populations of coated CRFs and can serve for further improving CRF production and performance.

  19. Compressibility and compactibility of granules produced by wet and dry granulation.

    Science.gov (United States)

    Bacher, C; Olsen, P M; Bertelsen, P; Sonnergaard, J M

    2008-06-24

    The bulk properties, compactibility and compressibility of granules produced by wet and dry granulation were compared applying a rotary tablet press, three different morphological forms of calcium carbonate and two particle sizes of sorbitol. Granules from both granulation methods possessed acceptable flow properties; however, the ground (Mikhart) and cubic (Scoralite) calcium carbonate demonstrated better die-filling abilities in the tablet press than the scalenhedral calcium carbonate (Sturcal). The wet processed granules showed in general larger compression properties. This was explained as these granules were mechanical stronger and had a higher initial porosity. In some cases, a large particle surface area of calcium carbonate and sorbitol resulted in a small, insignificant improvement of the consolidation characteristics. A correlation between the compression and compaction characteristics was demonstrated.

  20. A TECHNICAL NOTE ON GRANULATION TECHNOLOGY: A WAY TO OPTIMISE GRANULES

    Directory of Open Access Journals (Sweden)

    Mahammed Athar A. Saikh

    2013-01-01

    Full Text Available To provide an updated technical note on granulation technology (GT, mostly on novel GT, that will help researcher working/engaged in designing an efficient GT for getting granules with desired features. Granules were most widely used in the production of pharmaceutical oral dosage forms. Advancement in GT had revolutionized the sphere and resulted in development of several processes. Each and every process had advantages and disadvantages, and limitations. Depth knowledge in GT was a prerequisite to process product for obtaining targeted granulation with desired product parameters. In this regards updated literatures were collected from data bases, studied and was presented for easy reference of scientists engaged in granule production, so that they can adopt appropriate and suitable GT. Presented handy note will help researchers in designing a robust GT for getting optimised granule.

  1. THE STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT WAYS OF GRANULATION

    OpenAIRE

    Rybachuk VD

    2016-01-01

    Introduction. Active substances and excipients used in the manufacture of medicines in tablet form, in most cases, have poor technological properties. This fact determines the need for prior granulation of mass before compression. Granulators of various sizes and designs, running on different modes, made the formation, growth and consolidation of the powder particles that lead to obtain pellets of different shapes and sizes. From the literature it is known that granulation leads to two forms ...

  2. Ambiguous Phorate Granules for Sesame Seeds Linked to Accidental Organophosphate Fatal Poisoning

    Directory of Open Access Journals (Sweden)

    S Khatiwada

    2012-03-01

    Full Text Available Ingestion of organophosphate compound for suicidal attempt is a major health problem in developing countries. However, unintentional ingestion by an adult is rare. An 80-year-old lady and her 30-year-old granddaughter consumed phorate (organophosphate granules thinking it to be the seeds of sesame. After grinding the granules and mixing with pickle, they consumed the preparation with rice. The granddaughter was brought dead at emergency department and the older lady after resuscitation shifted to intensive care unit. She was extubated on 17th day and discharged on 23rd day. Pesticide formulation resembling any edible items must be withdrawn from the market at the earliest. Stringent regulation on vendors, apparent formulation or packaging and education about the hazards of these compounds can prevent this type of unintentional poisoning. Keywords: Ambiguous, organophosphate, phorate, sesame seeds, unintentional poisoning.

  3. Formulation Development and Optimization of Matrix Tablet of Tramadol Hydrochloride.

    Science.gov (United States)

    Deb, Pulak; Singha, Jubaraj; Chanda, Indranil; Chakraborty, Prithviraj

    2017-01-01

    The aim of the present investigation is to formulate and optimize oral sustained release matrix tablet of highly water soluble drug Tramadol HCl and to evaluate the effect of varying concentration of hydrophilic and hydrophobic polymer on drug release, based on a survey done on the recent patents of Tramadol HCl (US7374781, CA 2479252) and sustained release matrix tablets. The tablets were prepared by double granulation process, by melt granulation and wet granulation technique using Carnauba wax (CW) and HPMC K100 as release retardant. Pre and post compression factors were evaluated and all the parameters were found within the limit. The drug release data were subjected to different models in order to evaluate release kinetics and mechanism of drug release. The prepared formulations showed drug release in the range 100±2% in 6hrs, 7hrs, 8hrs and 9hrs and upto 12 hrs respectively. The optimized tablet having 25% CW and 20% HPMC showed sustained drug release pattern. Hydrophilic matrix of HPMC alone could not control the Tramadol release effectively for 12 h whereas when combined with CW could slow down the release of drug and can be successfully employed for formulating sustained-release matrix tablets. Similarity factor, f2 shows the test and reference profile are identical. Double granulation technique with CW and HPMC K100 proved as a better technique for sustaining the drug release from the matrix tablet. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  4. Cohesive strength of iron ore granules

    Directory of Open Access Journals (Sweden)

    Contreras Rafael Jaimes

    2017-01-01

    Full Text Available We present an experimental and numerical investigation of the mechanical strength of crude iron ore (Hematite granules in which capillary bonds between primary particles are the source of internal cohesion. The strength is measured by subjecting the granules to vertical compression between two plates. We show that the behavior of the granules is ductile with a well-defined plastic threshold which increases with the amount of water. It is found that the compressive strength scales with capillary cohesion with a pre-factor that is nearly independent of size polydispersity for the investigated range of parameters but increases with friction coefficient between primary particles. This weak dependence may be attributed to the class of fine particles which, due to their large number, behaves as a cohesive matrix that controls the strength of the granule.

  5. Cohesive strength of iron ore granules

    Science.gov (United States)

    Contreras, Rafael Jaimes; Berger, Nicolas; Izard, Edouard; Douce, Jean-François; Koltsov, Alexey; Delenne, Jean-Yves; Azema, Emilien; Nezamabadi, Saeid; van Loo, Frédéric; Pellenq, Roland; Radjai, Farhang

    2017-06-01

    We present an experimental and numerical investigation of the mechanical strength of crude iron ore (Hematite) granules in which capillary bonds between primary particles are the source of internal cohesion. The strength is measured by subjecting the granules to vertical compression between two plates. We show that the behavior of the granules is ductile with a well-defined plastic threshold which increases with the amount of water. It is found that the compressive strength scales with capillary cohesion with a pre-factor that is nearly independent of size polydispersity for the investigated range of parameters but increases with friction coefficient between primary particles. This weak dependence may be attributed to the class of fine particles which, due to their large number, behaves as a cohesive matrix that controls the strength of the granule.

  6. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    African Journals Online (AJOL)

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... physiological conditions: temperature, dehydration and nutritional condition. The main ... Granule content is released into the extra-cellular space (extrusion). The ANP causes .... Studies carried out in humans (Tanaka et al.,.

  7. Measuring stellar granulation during planet transits

    CERN Document Server

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

    2016-01-01

    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. We used realistic three-dimensional radiative hydrodynamical 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. We computed intensity maps from RHD simulations of the Sun and a K-dwarf star at different wavelength bands from optical to far-infrared. We modeled the transit using synthetic stellar-disk images and emulated the temporal variation of the granulation intensity. We identified two types of granulation noise that act simultaneously during the planet transit: (i) the intrinsic change in the granulation pattern with timescales smaller than the usual planet transit, and (ii) the fact that the transiting planet occults isolated regions of...

  8. Comparative study of erythritol and lactose monohydrate as carriers for inhalation: atomic force microscopy and in vitro correlation.

    Science.gov (United States)

    Traini, Daniela; Young, Paul M; Jones, Matthew; Edge, Stephen; Price, Robert

    2006-02-01

    The adhesion of micronised salbutamol sulphate to two carrier excipients, lactose monohydrate and erythritol, was investigated using the atomic force microscope (AFM) colloid probe technique and correlated with their respective physico-mechanical properties and aerosolisation performance. The particle size, morphology and moisture sorption properties of the carriers were similar thereby allowing direct comparison of functionality. AFM force measurements (n = 1024 force curves) were obtained between salbutamol sulphate drug probes (n = 4) and the excipients, as 63-90 microm sieve fractions and atomically smooth crystals. In general, significant differences in drug adhesion to lactose monohydrate and erythritol were observed (ANOVA, plactose monohydrate and drug probe adhesion to erythritol was established with salbutamol sulphate-lactose monohydrate adhesion being 60-70% of that of the erythritol system. In vitro analysis suggested good correlation with the adhesion measurements. The aerosolisation of salbutamol sulphate from erythritol carrier particles was significantly less (ANOVA, plactose monohydrate, with a fine particle dose (lactose monohydrate and erythritol carriers, respectively (n = 3).

  9. Acid resistance of starch granules

    Energy Technology Data Exchange (ETDEWEB)

    Nara, S.; Sakakura, M.; Komiya, T.

    1983-08-01

    When potato starch was hydrolyzed to form Naegeli amylodextrin by 16% sulfuric acid at 30/sup 0/C, only the amorphous portion of the starch granules was deteriorated. The crystallinity of Naegeli amylodextrin showing the hydrolysis ratio of 0.22 was 1.28 times as large as that of original starch. The hydrolysis process at above 45/sup 0/C was given by two exponential equations. The value of acid resistance portion (C/sub 0/) at 30 and 38/sup 0/C was 100%, while the values at 45, 50 and 55/sup 0/C were 67, 38 and 18%, respectively. The high value of C/sub 0/ generally showed the high acid resistance in the various starches. Sweet potato and waxy rice starches were more easily hydrolysed than other starches, although they gave the relatively high value of C/sub 0/. Thus, it was slightly more difficult for low acid resistance portion of potato starch to be hydrolyzed than for that of other starches. Moreover, that of waxy rice was easily hydrolyzed.

  10. Hippocampal granule cells opt for early retirement.

    Science.gov (United States)

    Alme, C B; Buzzetti, R A; Marrone, D F; Leutgeb, J K; Chawla, M K; Schaner, M J; Bohanick, J D; Khoboko, T; Leutgeb, S; Moser, E I; Moser, M-B; McNaughton, B L; Barnes, C A

    2010-10-01

    Increased excitability and plasticity of adult-generated hippocampal granule cells during a critical period suggests that they may "orthogonalize" memories according to time. One version of this "temporal tag" hypothesis suggests that young granule cells are particularly responsive during a specific time period after their genesis, allowing them to play a significant role in sculpting CA3 representations, after which they become much less responsive to any input. An alternative possibility is that the granule cells active during their window of increased plasticity, and excitability become selectively tuned to events that occurred during that time and participate in later reinstatement of those experiences, to the exclusion of other cells. To discriminate between these possibilities, rats were exposed to different environments at different times over many weeks, and cell activation was subsequently assessed during a single session in which all environments were revisited. Dispersing the initial experiences in time did not lead to the increase in total recruitment at reinstatement time predicted by the selective tuning hypothesis. The data indicate that, during a given time frame, only a very small number of granule cells participate in many experiences, with most not participating significantly in any. Based on these and previous data, the small excitable population of granule cells probably correspond to the most recently generated cells. It appears that, rather than contributing to the recollection of long past events, most granule cells, possibly 90-95%, are effectively "retired." If granule cells indeed sculpt CA3 representations (which remains to be shown), then a possible consequence of having a new set of granule cells participate when old memories are reinstated is that new representations of these experiences might be generated in CA3. Whatever the case, the present data may be interpreted to undermine the standard "orthogonalizer" theory of the role of

  11. Quantitative assessment of factors contributing to mottling of colored tablets II: formulation variables.

    Science.gov (United States)

    Armstrong, N A; March, G A

    1976-02-01

    The effects of several formulation variables were quantified with respect to factors affecting tablet mottling. Tablet mottling occurred with several commonly used binders and could not be prevented by using highly viscous binding solutions. However, mottling was reduced initially by increasing granule strength. Tablet diluents and dye-adsorbent materials had a profound effect on mottling, not by preventing dye migration but by affecting granule fragmentation on compression and the extent to which the dye-deficient material at the center of the granule was revealed. The lake form of FD&C Blue No. 1 was found to bleed in the presence of diluents that raised the pH of the granulating fluid above 6.4. Anionic impurities in the diluents also caused leaching of free dye and, consequently, increased tablet mottling. The conclusions from this study and previous papers were drawn together to give general principles for the production of uniformly colored tablets by aqueous granulation techniques.

  12. Intracranial localization of arachnoid granulations in rats

    Institute of Scientific and Technical Information of China (English)

    Yanan Dong; Min Yu; Lei Meng; Yong Jiang; Jun Gao; Honghai Peng; Jianguo Shi

    2008-01-01

    BACKGROUND: This paper describes histomorphologic studies on arachnoid granulations in rats, which have not been investigated in China to our knowledge.OBJECTIVE: To observe the distribution of intracranial arachnoid granulations in rats. DESIGN, TIME AND SETTING: The observational experiment was performed in the Academy of Life Sciences of Shandong Taishan Medical College from May to August 2004.MATERIALS: Thirty healthy adult Wistar rats (3-4 months old) of SPF grade, equal numbers of each sex, were selected for this study. Methylene blue parenteral solution was provided by Jiangsu Jichuan Pharmaceutical Company (China), and an optical microscope (Type: CH20; Olympus Co. Ltd., Japan) was used for observation of the histomorphology of the arachnoid granulations.METHOD: Injection of methylene blue parenteral solution into the cerebellomedullary cistern of rats.MAIN OUTCOME MEASURE: The blue stained parts of the lateral sinus were sectioned, stained by hematoxylin and eosin, and then observed under the microscope.RESULTS: The cavitas subarachnoidealis had extensive blue staining after methylene blue injection, while the arachnoid and dura were without dye accumulation. The blue dye indicated the location of the arachnoid granulations. The location of these granulations was fixed, mainly in the lateral sinus at both sides of confluence within 4 mm of the internal jugular vein.CONCLUSION: The arachnoid granulations of the rat were located mainly in the lateral sinuses of the dura mater.

  13. A preliminary pharmacognostical and pharmaceutical assay of Yastimadhu granules

    Directory of Open Access Journals (Sweden)

    Srihari Sheshagiri

    2012-01-01

    Full Text Available Aim: Yastimadhu (Glycyrrhizha glabra Linn. of Fabaceae family is one of the most commonly used herb in various Ayurvedic preparations with its vivid actions on various systems. It is also used as a flavouring agent and taste corrigent in pharmaceutical as well as confectionery industries. In a study conducted to evaluate the role of Yastimadhu in enhancing intellect and memory of school going children, the drug was used in the form of granules so ask to mask the issue of palatability. Pharmacognostical and physico-chemical properties were explored to assess the genuine nature of the raw drug in this new formulation after it underwent the pharmaceutical procedure. Materials and Methods: The present study provides the details of preparation of granules and methods employed in pharmacognostical and physic-chemical qualities. Results: The results obtained revealed that the genuine properties of raw drug did not change even after it underwent the pharmaceutical procedure into a new form which was easily palatable. Conclusion: As the drug possesses multiple actions and qualities, the new form would be of potential benefit to all age group of patients with issue of palatability. This study can also be used as a reference for further quality-control researches.

  14. Formulation and evaluation of naproxen sodium orodispersible tablets - A sublimation technique

    Directory of Open Access Journals (Sweden)

    Jeevanandham S

    2010-01-01

    Full Text Available The rationale of this investigation was to develop fast dissolving tablets of naproxen sodium using camphor as a subliming agent. Orodispersible tablets of naproxen sodium were prepared by the wet granulation technique using camphor as a subliming agent and sodium starch glycolate together with crosscarmellose sodium as superdisintegrants. Camphor was sublimed from the granules by exposing the granules to vacuum. The porous granules were then compressed into tablets. Alternatively, tablets were first prepared and later exposed to vacuum. The formulations were evaluated for weight variation, hardness, friability, drug content, wetting time, and in vitro dissolution. All the formulations showed low weight variation with dispersion time less than 55 s and rapid in vitro dissolution. Sublimation of camphor from tablets resulted in superior tablets as compared with the tablets prepared from granules that were exposed to vacuum. The results revealed that the tablets containing the subliming agent had a good dissolution profile. The drug content of all the formulations was within the acceptable limits of the United States Pharmacopoeia XXVII. The optimized formulation showed good release profile with maximum drug being released at all time intervals. It was concluded that fast dissolving tablets with improved naproxen sodium dissolution could be prepared by sublimation of tablets containing a suitable subliming agent. This work helped in understanding the effect of formulation processing variables especially the subliming agent on the drug release profile.

  15. Formulation and evaluation of antihelminthic polyherbal tablets

    Directory of Open Access Journals (Sweden)

    Dinesh Puri

    2011-01-01

    Full Text Available From time immemorial, man has been depending on plants as medicine. Helminthes infections are among the most common infections in man, affecting a large proportion of the world′s population. These helminthic diseases can be treated by various herbal drugs. The purpose of the present work was to formulate antihelminthic tablets. In this work, a spray dried-powder was used, which was obtained from the extract of different part of seven plants that were used in helminthic disease. The different tablets were prepared by using different types of disintegrating agents and various excipients. All parameters related to physicochemical property, trace metal and microbial examination of the spray-dried powder showed that these were within limits and could be used for the tablet formulation. The granules of the spray-dried powder were prepared by a wet granulation technique using isopropyl alcohol. The blends were evaluated for flow properties and for compressibility, which were found to be good. The tablets were prepared using a single rotatory punching machine, in which the punch size was 11 mm×8 mm, and formulated caplet-type tablets. These tablets were evaluated for the colour, odor, thickness and diameter, with visual inspection for any defects, weight variation, hardness, friability and in vitro disintegration time.

  16. Crystallisation of α-lactose monohydrate from dimethyl sulfoxide (DMSO) solutions: influence of β-lactose

    Science.gov (United States)

    Dincer, T. D.; Parkinson, G. M.; Rohl, A. L.; Ogden, M. I.

    1999-09-01

    In this study, the dimethyl sulfoxide (DMSO)-lactose system has been used to study the effect of β-lactose on the morphology of α-lactose monohydrate crystals. DMSO was used as the solvent as it greatly reduces the rate of mutarotation of α-lactose to β-lactose. It is shown that as the β-content of the solution increases, the crystal shape starts increasing in the a and b directions, whereas the major growth occurs in the c direction at low levels of β-lactose. The morphology of the α-lactose monohydrate crystal calculated by molecular modelling is in good agreement with that of the crystals grown in the presence of low β-lactose concentrations. Atomic force microscopy has revealed growth spirals and unit cell high steps on the (0 2 0) face of crystals grown in the presence of low β-anomer concentration.

  17. Crystal growth mechanisms of the (0 1 0) face of α-lactose monohydrate crystals

    Science.gov (United States)

    Dincer, T. D.; Ogden, M. I.; Parkinson, G. M.

    2009-04-01

    The growth rates of the (0 1 0) face of α-lactose monohydrate crystals were measured at 30, 40 and 50 °C in the relative supersaturation range 0.55-2.33 in aqueous solutions. The mechanisms of growth were investigated. Spiral growth was found to be the mechanism of growth up to a critical relative supersaturation ( s-1) crit=1.9 at 30 °C. Above the critical relative supersaturation, the crystal growth mechanisms were predicted to change. All growth models fit equally well to the growth rates. No two-dimensional nucleation was observed above critical supersaturation by AFM. On the other hand increased step height and roughness on the edges of steps were observed. It was concluded that the growth mechanism of the (0 1 0) face of α-lactose monohydrate crystal is spiral growth. A parabolic relationship was obtained below critical supersaturation followed by a linear relationship with relative supersaturation.

  18. Study of light scattering by a granulated coated sphere - a model of granulated blood cells

    NARCIS (Netherlands)

    M.A. Yurkin; D. de Kanter; A.G. Hoekstra

    2008-01-01

    We performed extensive simulations of light scattering by granulated coated sphere model using the discrete dipole approximation and varying model parameters in the ranges of sizes and refractive indices of granulated blood cells. We compared these results with predictions of Maxwell-Garnett effecti

  19. Granule size control and targeting in pulsed spray fluid bed granulation.

    Science.gov (United States)

    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.

  20. Eosinophil secretion of granule-derived cytokines

    Directory of Open Access Journals (Sweden)

    Lisa A Spencer

    2014-10-01

    Full Text Available Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include: classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines.

  1. Pharmacokinetic Comparison of Omeprazole Granule and Suspension Forms in Children: A Randomized, Parallel Pilot Trial.

    Science.gov (United States)

    Karami, S; Dehghanzadeh, G; Haghighat, M; Mirzaei, R; Rahimi, H R

    2016-03-01

    Although, omeprazole is widely used for treatment of gastric acid-mediated disorders. However, its pharmacokinetic and chemical instability does not allow simple aqueous dosage form formulation synthesis for therapy of, especially child, these patients. The aim of this study was at first preparation of suspension dosage form omeprazole and second to compare the blood levels of 2 oral formulations/dosage forms of suspension & granule by high performance liquid chromatography (HPLC). The omeprazole suspension was prepared; in this regard omeprazole powder was added to 8.4% sodium bicarbonate to make final concentration 2 mg/ml omeprazole. After that a randomized, parallel pilot trial study was performed in 34 pediatric patients with acid peptic disorder who considered usage omeprazole. Selected patients were received suspension and granule, respectively. After oral administration, blood samples were collected and analyzed for omeprazole levels using validated HPLC method. The mean omeprazole blood concentration before usage the next dose, (trough level) were 0.12±0.08 µg/ml and 0.18±0.15 µg/ml for granule and suspension groups, respectively and mean blood level after dosing (C2 peak level) were 0.68±0.61 µg/ml and 0.86±0.76 µg/ml for granule and suspension groups, respectively. No significant changes were observed in comparison 2 dosage forms 2 h before (P=0.52) and after (P=0.56) the last dose. These results demonstrate that omeprazole suspension is a suitable substitute for granule in pediatrics.

  2. Structure and vibrational spectra of L-alanine L-alaninium picrate monohydrate

    Science.gov (United States)

    Ghazaryan, V. V.; Fleck, M.; Petrosyan, A. M.

    2012-05-01

    Preparation, crystal and molecular structure as well as vibrational spectra of the crystal L-alanine L-alaninium picrate monohydrate are described. The title crystal is monoclinic, space group P21. The asymmetric unit contains one dimeric (L-Ala⋯L-Ala+) cation, one picrate anion and a water molecule. The O⋯O distance in the dimeric cation is equal to 2.553(2) Å. The IR and Raman spectra are interpreted based on the structure.

  3. Aerobic granulation of protein-rich granules from nitrogen-lean wastewaters.

    Science.gov (United States)

    Chen, Yu-You; Ju, Sheau-Pyng; Lee, Duu-Jong

    2016-10-01

    Proteins (PN)-rich granules are stable in structure in long-term reactor operations. This study proposed to cultivate PN-rich granules with PN/polysaccharides (PS) >20 from nitrogen lean wastewater, with ammonia-nitrogen as sole nitrogen source at chemical oxygen demand (COD)/N of 153.8. The yielded granules can sustain their structural stability in sequencing batch reactor mode for sufficient treatment of wastewaters up to 7000mg/L COD and with COD/Nnitrogen fed in the nitrogen-lean wastewater is converted to the PN in the granules. The replacement of ammonia by nitrate as sole nitrogen source led to granules enriched with γ-proteobacteria which are easily deteriorated at low OLR.

  4. Creatine monohydrate increases bone mineral density in young Sprague-Dawley rats.

    Science.gov (United States)

    Antolic, Anamaria; Roy, Brian D; Tarnopolsky, Mark A; Zernicke, Ronald F; Wohl, Gregory R; Shaughnessy, Stephen G; Bourgeois, Jacqueline M

    2007-05-01

    Creatine kinase, found in osteoblasts, is an enzyme that is upregulated in response to interventions that enhance bone mass accretion. Creatine monohydrate supplementation can increase fat-free mass in young healthy men and women and can reduce markers of bone breakdown in boys with Duchenne muscular dystrophy. The objective of this study was to determine the influence of supplementation with creatine monohydrate on bone structure and function in growing rats, to establish a therapeutic model. Creatine monohydrate (2% w.w.) (CR; N = 16) or standard rat chow (CON; N = 16) was fed to Sprague-Dawley rats beginning at 5 wk of age, for 8 wk. Bone mineral density (BMD) and content (BMC) were assessed using dual-energy x-ray absorptiometry at the beginning and end of the protocol. The rats were sacrificed, and one femur was removed for the determination of mechanical properties. The CR-treated rats showed greater lumbar BMD and femoral bending load at failure compared with the CON rats (P properties and its effects in disorders associated with bone loss.

  5. A combined modelling and experimental study of the surface energetics of alpha-lactose monohydrate.

    Science.gov (United States)

    Saxena, A; Kendrick, J; Grimsey, I M; Roberts, R; York, P

    2010-02-01

    The surface energy of alpha-lactose monohydrate measured by inverse gas chromatography (IGC) is reported along with a dynamic molecular modelling study of the interaction of the various molecular probes with different surfaces of alpha-lactose monohydrate. The IGC results show that alpha-lactose monohydrate is acidic in nature. Using quantitative calculations of the energy of adsorption, the acidic nature of the surface is confirmed and the calculated values agree closely with the experimentally measured values. Along with the acidic nature, dynamic molecular modelling also reveals that the presence of a channel and water molecules on a surface affects the surface energetics of that face. The presence of water on the surface can decrease or increase the surface energy by either blocking or attracting a probe molecule, respectively. This property of water depends on its position and association with other functional groups present on the surface. The effect of a channel or cavity on the surface energy is shown to depend on its size, which determines whether the functional groups in the channel are assessable by probe molecules or not. Overall molecular modelling explains, at the molecular level, the effect of different factors affecting the surface energy of individual faces of the crystal. (c) 2009 Wiley-Liss, Inc. and the American Pharmacists Association.

  6. Simultaneous Determination of Sitagliptin Phosphate Monohydrate and Metformin Hydrochloride in Tablets by a Validated UPLC Method.

    Science.gov (United States)

    Malleswararao, Chellu S N; Suryanarayana, Mulukutla V; Mukkanti, Khagga

    2012-01-01

    A novel approach was used to develop and validate a rapid, specific, accurate and precise reverse phase ultra performance liquid chromatographic (UPLC) method for the simultaneous determination of Sitagliptin phosphate monohydrate and Metformin hydrochloride in pharmaceutical dosage forms. The chromatographic separation was achieved on Aquity UPLC BEH C8 100 × 2.1 mm, 1.7 μm, column using a buffer consisting of 10 mM potassium dihydrogen phosphate and 2 mM hexane-1-sulfonic acid sodium salt (pH adjusted to 5.50 with diluted phosphoric acid) and acetonitrile as organic solvent in a gradient program. The flow rate was 0.2 mL min(-1) and the detection wavelength was 210 nm. The limit of detection (LOD) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.2 and 0.06 μg mL(-1), respectively. The limit of quantification (LOQ) for Sitagliptin phosphate monohydrate and Metformin hydrochloride was 0.7 and 0.2 μg mL(-1), respectively. This method was validated with respect to linearity, accuracy, precision, specificity and robustness. The method was also found to be stability-indicating.

  7. Slow- Release Fertilizer Formulation Using Acrylic and Chitosan Coating

    Directory of Open Access Journals (Sweden)

    Lili Handayani

    2015-01-01

    Full Text Available The low-efficiency problem in fertilizer application can be overcome by controlling fertilizer solubility, i.e. by rendering the fertilizer to be released gradually; such material is also known as slow-release fertilizer (SRF. This research was aimed to formulate SRF by coating technique using acrylic and chitosan as the coating material, and to evaluate fertilizer resistance to too fast disintegration, and rate of nutrient release method. The results demonstrated that fertilizer formulation containing N, P, K, Fe, Cu, and Zn with granulation technique yielded 74% of granules with 2-5 mm in diameter. The SRFs (formulated fertilizer with acrylic or chitosan coating were more resistant to water pounding than non-SRF. Furthermore, shaking test with distilled water or 2% citric acid, or by percolation test with distilled water showed that the SRFs had lower nutrient solubility than the non-SRFs. The results of shaking test also specifically indicated that coating with acrylic made the fertilizer more resistant to the citric acid,suggesting that this coating material would be more suitable in acidic soils. The SRFs formulated with the addition of chitosan during blending of micronutrients prior to mixing with macronutrients, granulation, and final coating exhibited lower nutrient solubility than the SRFs without the pre-coating chitosan addition.

  8. Formation of volutin granules in Corynebacterium glutamicum.

    Science.gov (United States)

    Pallerla, Srinivas Reddy; Knebel, Sandra; Polen, Tino; Klauth, Peter; Hollender, Juliane; Wendisch, Volker F; Schoberth, Siegfried M

    2005-02-01

    Volutin granules are intracellular storages of complexed inorganic polyphosphate (poly P). Histochemical staining procedures differentiate between pathogenic corynebacteria such as Corynebacterum diphtheriae (containing volutin) and non-pathogenic species, such as C. glutamicum. Here we report that strains ATCC13032 and MH20-22B of the non-pathogenic C. glutamicum also formed subcellular entities (18-37% of the total cell volume) that had the typical characteristics of volutin granules: (i) volutin staining, (ii) green UV fluorescence when stained with 4',6-diamidino-2-phenylindole, (iii) electron-dense and rich in phosphorus when determined with transmission electron microscopy and X-ray microanalysis, and (iv) 31P NMR poly P resonances of isolated granules dissolved in EDTA. MgCl2 addition to the growth medium stimulated granule formation but did not effect expression of genes involved in poly P metabolism. Granular volutin fractions from lysed cells contained polyphosphate glucokinase as detected by SDS-PAGE/MALDI-TOF, indicating that this poly P metabolizing enzyme is present also in intact poly P granules. The results suggest that formation of volutin is a more widespread phenomenon than generally accepted.

  9. Amylase activity in substrate deficiency aerobic granules.

    Science.gov (United States)

    Lee, Chuen-Chi; Lee, Duu-Jong; Lai, Juin-Yih

    2009-01-01

    Immunohistochemical staining was applied together with the multicolor fluorescent scheme to demonstrate the amylase activity for polysaccharide hydrolysis in stored or starved aerobic granules that are in substrate deficiency. If sufficient nutrients were present, alpha-amylase and beta-amylase were found close to the surface layer of the original granules. Following storage or starvation during which most external nutrients were depleted, the alpha-amylase and beta-amylase were distributed over the entire granule interior, suggesting endogenous respiration at the core of the granule. In particular, the fluorescent intensities of alpha-amylase and beta-amylase were enriched 5-20 microm from the edge of the internal cavity, suggesting the strong correlation between polysaccharide hydrolysis and the formation of interior cavities. The secreted amylase was located near the living cells, suggesting that the polysaccharide hydrolysis is restricted to local environment that occurs near the functional strains. Internal hydrolysis within the core, for the case of both proteins and polysaccharides should correspond in principle to the loss of granule stability.

  10. Formulation and evaluation of CFC free inhalers for beclomethasone dipropionate

    Directory of Open Access Journals (Sweden)

    Gopala Krishna Murthy Talasila

    2013-06-01

    Full Text Available Beclomethasone dipropionate CFC free inhalation formulations were developed with a view to treat asthma prophylactically. Dry powder inhalers (DPI for beclomethasone dipropionate were prepared with different grades of lactose monohydrate. The influence of carrier and overages on performance of DPI was studied. Metered dose inhalers (MDI with HFA based propellants were formulated with various doses, overages and different concentrations of alcohol. Formulated DPI and MDI were evaluated for various official and unofficial quality control tests. The influence of over doses on valve delivery, effect of overages on emitted dose and influence of alcohol on spray pattern from MDI were studied. The better fine particle fraction and emitted dose were obtained from the DPI formulated with 10:90 ratio of fine lactose: coarse lactose and with 20% w/w overages. The studies on MDI revealed that the 15% of overdoses are required for effective valve delivery and 20% overages are required for 100% drug delivery. 5-10%v/v alcohol was found to be preferable to get optimum emitted dose and fine particle fraction.

  11. Profile of sodium phenylbutyrate granules for the treatment of urea-cycle disorders: patient perspectives.

    Science.gov (United States)

    Peña-Quintana, Luis; Llarena, Marta; Reyes-Suárez, Desiderio; Aldámiz-Echevarria, Luis

    2017-01-01

    Urea-cycle disorders are a group of rare hereditary metabolic diseases characterized by deficiencies of one of the enzymes and transporters involved in the urea cycle, which is necessary for the removal of nitrogen produced from protein breakdown. These hereditary metabolic diseases are characterized by hyperammonemia and life-threatening hyperammonemic crises. Pharmacological treatment of urea-cycle disorders involves alternative nitrogen-scavenging pathways. Sodium benzoate combines with glycine and phenylacetate/phenylbutyrate with glutamine, forming, respectively, hippuric acid and phenylacetylglutamine, which are eliminated in the urine. Among the ammonia-scavenging drugs, sodium phenylbutyrate is a well-known long-term treatment of urea-cycle disorders. It has been used since 1987 as an investigational new drug, and was approved for marketing in the US in 1996 and the EU in 1999. However, sodium phenylbutyrate has an aversive odor and taste, which may compromise patients' compliance, and many patients have reported difficulty in taking this drug. Sodium phenylbutyrate granules are a new tasteless and odor-free formulation of sodium phenylbutyrate, which is indicated in the treatment of urea-cycle disorders. This recently developed taste-masked formulation of sodium phenylbutyrate granules was designed to overcome the considerable issues that taste has on adherence to therapy. Several studies have reported the clinical experience of patients with urea-cycle disorders treated with this new tasteless formulation of sodium phenylbutyrate. Analysis of the data indicated that this taste-masked formulation of sodium phenylbutyrate granules improved quality of life for urea-cycle disorder patients. Furthermore, a postmarketing report on the use of the product has confirmed the previous observations of improved compliance, efficacy, and safety with this taste-masked formulation of sodium phenylbutyrate.

  12. Crystallization Formulation Lab

    Data.gov (United States)

    Federal Laboratory Consortium — The Crystallization Formulation Lab fills a critical need in the process development and optimization of current and new explosives and energetic formulations. The...

  13. Measuring stellar granulation during planet transits

    Science.gov (United States)

    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

  14. Antimicrobial-Coated Granules for Disinfecting Water

    Science.gov (United States)

    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.

  15. MEMBRANE-COATING GRANULES OF KERATINIZING EPITHELIA.

    Science.gov (United States)

    MATOLTSY, A G; PARAKKAL, P F

    1965-02-01

    The purpose of this study has been to obtain information on the development of the envelop of horny cells that resists the action of keratinolytic agents. Toward this end the epidermis, oral mucosa, and tongue epithelium of various vertebrates, as well as the isolated envelopes of horny cells, were examined by electron microscopy. It was found that small cytoplasmic granules (1,000 to 5,000 A) that develop within differentiating epithelial cells move toward the cell periphery, and after fusion with the plasma membrane, empty their contents into the intercellular spaces. The content of the granules spreads over the cell surfaces, and subsequently a thickened and coated cell envelope is formed that resists the action of keratinolytic agent. The membrane-coating granule is regarded as a specific differentiation product of the keratinizing epithelium. It contains numerous inner membranes and is assumed to engage in synthetic activities such as, perhaps, the formation of polysaccharides.

  16. Formulation and optimization of carbamazepine floating tablets

    Directory of Open Access Journals (Sweden)

    Patel D

    2007-01-01

    Full Text Available Floating tablets of carbamazepine were developed using melt granulation technique. Bees wax was used as a hydrophobic meltable material. Hydroxypropylmethylcellulose, sodium bicarbonate and ethyl cellulose were used as matrixing agent, gas-generating agent and floating enhancer, respectively. The tablets were evaluated for in vitro buoyancy and dissolution studies. A simplex lattice design was applied to investigate the combined effect of 3 formulation variables i.e. amount of hydroxypropyl methylcellulose ( X 1 , ethyl cellulose ( X 2 and sodium bicarbonate ( X 3 . The floating lag time (F lag , time required for 50% (t 50 and 80% drug dissolution (t 80 were taken as responses. Results of multiple regression analysis indicated that, low level of X 1 and X 2 , and high level of X 3 should be used to manufacture the tablet formulation with desired in vitro floating time and dissolution. Formulations developed using simplex lattice design were fitted to various kinetic models for drug release. Formulation S3 was selected as a promising formulation and was found stable at 40 o and 75% relative humidity for 3 months. Present study demonstrates the use of simplex lattice design in the development of floating tablets with minimum experimentation.

  17. Arachnoid granulation affected by subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    R.P. Chopard

    1993-11-01

    Full Text Available The purpose of this study was to investigate using light microscopy the fibro-cellular components of arachnoid granulations affected by mild and severe subarachnoid hemorrage. The erythrocytes were in the channels delimitated by collagenous and elastic bundles and arachnoid cells, showing their tortuous and intercommunicating row from the pedicle to the fibrous capsule. The core portion of the pedicle and the center represented a principal route to the bulk outflow of cerebrospinal fluid and erythrocytes. In the severe hemorrhage, the fibrocellular components are desorganized, increasing the extracellular channels. We could see arachnoid granulations without erythrocytes, which cells showed big round nucleous suggesting their transformation into phagocytic cells.

  18. Molecular composition of IMP1 ribonucleoprotein granules

    DEFF Research Database (Denmark)

    Jønson, Lars; Vikesaa, Jonas; Krogh, Anders

    2007-01-01

    Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization, and in mo......Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization...

  19. Neutrophil granules in health and disease

    DEFF Research Database (Denmark)

    Häger, M; Cowland, J B; Borregaard, N

    2010-01-01

    Neutrophil granules store proteins that are critically important for the neutrophil to move from the vascular bed to tissues and to kill microorganisms. This is illustrated in nature when individual proteins are deleted due to inherited mutations of their cognate genes, and such deficiencies result...... in the conditions leucocyte adhesion deficiency and chronic granulomatous disease. The granules of the neutrophil have traditionally been divided into two or three major types but are instead a continuum where several subtypes can be identified with differences in protein content and propensity for mobilization...

  20. Carcinogenicity and chronic toxicity of hydrazine monohydrate in rats and mice by two-year drinking water treatment.

    Science.gov (United States)

    Matsumoto, Michiharu; Kano, Hirokazu; Suzuki, Masaaki; Katagiri, Taku; Umeda, Yumi; Fukushima, Shoji

    2016-04-01

    The carcinogenicity and chronic toxicity of hydrazine monohydrate was examined by administrating hydrazine monohydrate in drinking water to groups of 50 F344/DuCrj rats and 50 Crj:BDF1 mice of both sexes for two years. The drinking water concentration of hydrazine monohydrate was 0, 20, 40 or 80 ppm (wt/wt) for male and female rats and male mice; and 0, 40, 80 or 160 ppm for female mice. Survival rates of each group of males and females rats and mice were similar to the respective controls, except female rats administered 80 ppm. Two-year administration of hydrazine monohydrate produced an increase in the incidences of hepatocellular adenomas and carcinomas in rats of both sexes along with hepatic foci. In mice, the incidences of hepatocellular adenomas and carcinomas were increased in females, and significantly increased incidences of hepatocellular adenomas in females administered 160 ppm were observed. Thus, hydrazine monohydrate is carcinogenic in two species, rats and mice. Additionally, non-neoplastic renal lesions in rats and mice and non-neoplastic nasal lesions in mice were observed.

  1. Rock mechanics modeling based on soft granulation theory

    CERN Document Server

    Owladeghaffari, H

    2008-01-01

    This paper describes application of information granulation theory, on the design of rock engineering flowcharts. Firstly, an overall flowchart, based on information granulation theory has been highlighted. Information granulation theory, in crisp (non-fuzzy) or fuzzy format, can take into account engineering experiences (especially in fuzzy shape-incomplete information or superfluous), or engineering judgments, in each step of designing procedure, while the suitable instruments modeling are employed. In this manner and to extension of soft modeling instruments, using three combinations of Self Organizing Map (SOM), Neuro-Fuzzy Inference System (NFIS), and Rough Set Theory (RST) crisp and fuzzy granules, from monitored data sets are obtained. The main underlined core of our algorithms are balancing of crisp(rough or non-fuzzy) granules and sub fuzzy granules, within non fuzzy information (initial granulation) upon the open-close iterations. Using different criteria on balancing best granules (information pock...

  2. Granulate of stainless steel as compensator material

    NARCIS (Netherlands)

    J.P.C. van Santvoort (J. P C)

    1995-01-01

    textabstractCompensators produced with computer controlled milling devices usually consist of a styrofoam mould, filled with an appropriate material. We investigated granulate of stainless steel as filling material. This cheap, easy to use, clean and re-usable material can be obtained with an averag

  3. Structural studies on methylated starch granules

    NARCIS (Netherlands)

    Vliegenthart, J.F.G.; Burgt, Y.E.M. van der; Bergsma, J.; Bleeker, I.P.; Mijland, P.J.H.C.; Kamerling, J.P.

    2000-01-01

    Granules of potato starch and amylopectin potato starch were methylated in aqueous alkaline suspension. Here, an overview is given of all structural aspects that have been studied with respect to the determination of the location of the substituents. Methods, which are generally applicable, were

  4. Starch Granule Variability in Wild Solanum Species

    Science.gov (United States)

    Because most of the dry matter of potato tubers is starch, an understanding of starch properties is important in potato improvement programs. Starch granule size is considered to influence tuber processing quality parameters such as gelatinization temperature, viscosity, and water holding capacity. ...

  5. Neutrophil granules in health and disease

    DEFF Research Database (Denmark)

    Häger, M; Cowland, J B; Borregaard, N

    2010-01-01

    Neutrophil granules store proteins that are critically important for the neutrophil to move from the vascular bed to tissues and to kill microorganisms. This is illustrated in nature when individual proteins are deleted due to inherited mutations of their cognate genes, and such deficiencies resu...

  6. Creep of granulated loose-fill insulation

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn

    with SP-Building Physics in Sweden and VTT Building Technology in Finland. For the round robin test a cellulosic fibre insulation material was used. The proposed standardised method for creep tests and theories are limited to cases when the granulated loose-fill material is exposed to a constant...

  7. Apatite accumulation enhances the mechanical property of anammox granules

    NARCIS (Netherlands)

    Lin, Y. M.; Lotti, T.; Sharma, P. K.; van Loosdrecht, M. C. M.

    2013-01-01

    The strength of granular sludge is essential for the mechanical stability of the granules. Inorganic precipitants form a major factor influencing the strength of the granules. To check the possibility of apatite accumulation in anammox granules, and study its contribution to the mechanical strength

  8. Mechanistic modelling of fluidized bed drying processes of wet porous granules

    DEFF Research Database (Denmark)

    Mortier, Séverine Thérèse F.C.; De Beer, Thomas; Gernaey, Krist;

    2011-01-01

    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...... 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...... 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....

  9. A PRELIMINARY PHARMACOGNOSTICAL AND PHYSICO CHEMICAL ASSAY OF HARIDRA KHANDA GRANULES: A PILOT STUDY

    Directory of Open Access Journals (Sweden)

    Chaudhari Varsha M.

    2011-06-01

    Full Text Available Haridra Khanda is mentioned in the management of skin diseases like Urticaria (Udarda Shitpitta Kotha. Most of the ingredients are having properties to control allergic condition and improve Vyadhikshamatva (Immuno-modulatory. Pratishyaya (Rhinitis is one of the common problem since ancient days; among all type of Rhinitis, Vataja type simulates the Allergic Rhinitis in modern medical literature of ENT. To overcome the problem of fungus formation in Khanda and AvalehaKalpana, Haridra Khanda has been prepared in granules form. In this study, effort has been done to overcome from the controversy regarding ingredients in the finished product and tried to make it standardized as per guidelines of API. Pharmacognostically authenticated raw drugs were used for the preparation of granules and it was analyzed through qualitative and quantitative analysis of Physico – chemical parameters. It is inferred that the formulation meets the minimum qualitative standards as reported in the API and AFI at a preliminary level.

  10. A numerical approach to drying process of hygroscopic polymeric granulates with different drying configurations and parameter comparison

    Science.gov (United States)

    Mahbub, A. M. Ishtiaque; Mawa, Zannatul

    2017-06-01

    Some polymers tend to possess affinity with water and eventually, absorb significant moisture content from the surrounding air, causing difficulties during their industrial processing. Drying of these hygroscopic polymers, therefore, plays a vital role in their usability in industrial applications. In this work, the drying kinetics of the polymeric granulates is numerically formulated and the influence of different parameters pertaining to the drying procedure has been investigated. Backward Euler or implicit algorithm has been considered for solving the second order partial differential heat and mass transfer equations for simulating the drying kinetics of Polyamide 6 (PA-6). At first, the conduction of heat from the granulate surface towards the core was formulated using one dimensional transient heat conduction law and corresponding diffusion coefficients were determined using Arrhenius diffusion model. Afterwards, the migration of moisture from the granulate core towards the surface has been calculated using Fick's second law of diffusion. The data obtained from the single polymer granulate was then used to calculate the amount of moisture removed and the drying rate. The numerical results showed similitude with the experimental data obtained from the literature, although deviated quantitatively. To investigate the influence of different parameters on the drying process, different cases with varying drying air temperature, granulate radius and initial moisture content were compared. The numerical analysis qualitatively predicted all the dependencies to be expected. With higher drying air temperature, drying rate was observed to be faster and with higher granulate radius, drying rate was slower. With better approximations of the applied parameters and algorithms, the accuracy of the developed numerical model could be improved and used as a prediction tool for the drying process of polymer samples with reasonable tolerance.

  11. Polyamines are present in mast cell secretory granules and are important for granule homeostasis.

    Directory of Open Access Journals (Sweden)

    Gianni García-Faroldi

    Full Text Available BACKGROUND: Mast cell secretory granules accommodate a large number of components, many of which interact with highly sulfated serglycin proteoglycan (PG present within the granules. Polyamines (putrescine, spermidine and spermine are absolutely required for the survival of the vast majority of living cells. Given the reported ability of polyamines to interact with PGs, we investigated the possibility that polyamines may be components of mast cell secretory granules. METHODOLOGY/PRINCIPAL FINDINGS: Spermidine was released by mouse bone marrow derived mast cells (BMMCs after degranulation induced by IgE/anti-IgE or calcium ionophore A23187. Additionally, both spermidine and spermine were detected in isolated mouse mast cell granules. Further, depletion of polyamines by culturing BMMCs with α-difluoromethylornithine (DFMO caused aberrant secretory granule ultrastructure, impaired histamine storage, reduced serotonin levels and increased β-hexosaminidase content. A proteomic approach revealed that DFMO-induced polyamine depletion caused an alteration in the levels of a number of proteins, many of which are connected either with the regulated exocytosis or with the endocytic system. CONCLUSIONS/SIGNIFICANCE: Taken together, our results show evidence that polyamines are present in mast cell secretory granules and, furthermore, indicate an essential role of these polycations during the biogenesis and homeostasis of these organelles.

  12. Experimental investigation of granule size and shape dynamics in twin-screw granulation.

    Science.gov (United States)

    Kumar, Ashish; Vercruysse, Jurgen; Bellandi, Giacomo; Gernaey, Krist V; Vervaet, Chris; Remon, Jean Paul; De Beer, Thomas; Nopens, Ingmar

    2014-11-20

    A twin-screw granulator (TSG), a promising equipment for continuous high shear wet granulation (HSWG), achieves the desired level of mixing by a combination of the appropriate screw configuration and a suitable set of process settings (e.g. feed rate, screw speed, etc.), thus producing a certain granule size and shape distribution (GSSD). However, the primary sizing and shaping mechanism behind the resulting distribution is not well understood due to the opacity of the multiphase system in the granulator. This study experimentally characterised the GSSD dynamics along the TSG barrel length in order to understand the function of individual screw modules and process settings, as well as their interaction. Particle size analysis of granules collected at the outlet of the TSG suggested significant interaction between the process and screw configuration parameters influencing the heterogeneity in the GSSD. By characterising the samples collected along the screw length, a variable influence of the screw modules at different process conditions was observed. At low liquid-to-solid ratio (L/S), the first kneading module seemed to play a significant role in mixing, whereas the second kneading module was found to be more involved in reshaping the granules. At high L/S and high throughput, aggregation mainly took place in the second kneading module changing the GSSD. The results obtained from this study will be further used for the calibration and validation of a mechanistic model and, hence, support future development of a more detailed understanding of the HSWG process in a TSG.

  13. Novel montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats.

    Science.gov (United States)

    Kim, Dong Wuk; Kim, Young Hun; Yousaf, Abid Mehmood; Kim, Dong Shik; Kwon, Taek Kwan; Park, Jung Hee; Kim, Yong Il; Park, Jae-Hyun; Jin, Sung Giu; Kim, Kyung Soo; Cho, Kwan Hyung; Li, Dong Xun; Kim, Jong Oh; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2016-04-01

    To develop a montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats, several montelukast sodium-loaded suspensions were prepared with a suspending agent, stabilizers and anti-aggregation agents, and their stabilities were investigated by visually observing the sedimentation phenomenon and determining the concentration of the degradation product. Moreover, dissolution and pharmacokinetic studies of the optimized formulation were examined in rats compared to commercial montelukast sodium-loaded granules. Avicel RC-591 (Avicel), a suspending agent, prevented the sedimentation of these suspensions at >2.496 (w/v) per cent composition. Amongst the stabilizers tested, fumaric acid provided the lowest concentration of montelukast sulphoxide (a degradation product) in these suspensions at 40 °C, demonstrating its excellent stabilizing activity. Furthermore, as an anti-aggregation agent, glycerin gave lower amounts of degradation product than those with poloxamer 407 and Tween 80. In particular, montelukast-loaded oral suspension, an aqueous suspension containing montelukast sodium/Avicel/fumaric acid/glycerin at a concentration of 312/2496/15.6/62.4 (mg/100 ml), and the commercial granules exhibited similar dissolution profiles in 0.5% (w/v) aqueous solution of sodium lauryl sulphate. Moreover, the pharmacokinetics in rats provided by this suspension was comparable to that of the commercial granules, suggesting that they were bioequivalent. In addition, it was physically and chemically stable at 40 °C for at least 6 months. Thus, this montelukast sodium-loaded oral suspension, with bioequivalence to the commercial granules and excellent stability, could be a prospective dosage form for the treatment of asthma.

  14. Microbial starch binding domains are superior to granule bound starch synthase 1 for anchoring luciferase to potato starch granules

    NARCIS (Netherlands)

    Ji, Q.; Vincken, J.P.; Suurs, L.C.J.M.; Visser, R.G.F.

    2006-01-01

    Microbial starch-binding domains (SBD) and granule-bound starch synthase I (GBSSI) are proteins which are accumulated in potato starch granules. The efficiency of SBD and GBSSI for targeting active luciferase reporter proteins to granules during starch biosynthesis was compared. GBSSI or SBD sequenc

  15. Radiolysis of Sulfuric Acid, Sulfuric Acid Monohydrate, and Sulfuric Acid Tetrahydrate and Its Relevance to Europa

    Science.gov (United States)

    Loeffler, M. J.; Hudson, R. L.; Moore, M. H.; Carlson, R. W.

    2011-01-01

    We report laboratory studies on the 0.8 MeV proton irradiation of ices composed of sulfuric acid (H2SO4), sulfuric acid monohydrate (H2SO4 H2O), and sulfuric acid tetrahydrate (H2SO4 4H2O) between 10 and 180 K. Using infrared spectroscopy, we identify the main radiation products as H2O, SO2, (S2O3)x, H3O+, HSO4(exp -), and SO4(exp 2-). At high radiation doses, we find that H2SO4 molecules are destroyed completely and that H2SO4 H2O is formed on subsequent warming. This hydrate is significantly more stable to radiolytic destruction than pure H2SO4, falling to an equilibrium relative abundance of 50% of its original value on prolonged irradiation. Unlike either pure H2SO4 or H2SO4 H2O, the loss of H2SO4 4H2O exhibits a strong temperature dependence, as the tetrahydrate is essentially unchanged at the highest irradiation temperatures and completely destroyed at the lowest ones, which we speculate is due to a combination of radiolytic destruction and amorphization. Furthermore, at the lower temperatures it is clear that irradiation causes the tetrahydrate spectrum to transition to one that closely resembles the monohydrate spectrum. Extrapolating our results to Europa s surface, we speculate that the variations in SO2 concentrations observed in the chaotic terrains are a result of radiation processing of lower hydration states of sulfuric acid and that the monohydrate will remain stable on the surface over geological times, while the tetrahydrate will remain stable in the warmer regions but be destroyed in the colder regions, unless it can be reformed by other processes, such as thermal reactions induced by diurnal cycling.

  16. Crystal studies, vibrational spectra and non-linear optical properties of L-histidine chloride monohydrate.

    Science.gov (United States)

    Ben Ahmed, A; Feki, H; Abid, Y; Boughzala, H; Minot, C

    2010-01-01

    This paper presents the results of our calculations on the geometric parameters, vibrational spectra and hyperpolarizability of a non-linear optical material L-histidine chloride monohydrate. Due to the lack of sufficiently precise information on geometric parameters available in literature, theoretical calculations were preceded by re-determination of the crystal X-ray structure. Single crystal of L-histidine chloride monohydrate has been growing by slow evaporation of an aqueous solution at room temperature. The compound crystallizes in the non-Centro-symmetric space group P2(1)2(1)2(1) of orthorhombic system. IR spectrum has been recorded in the range [400-4000 cm(-1)]. All the experimental vibrational bands have been discussed and assigned to normal mode or to combinations on the basis of our calculations. The optimized geometric bond lengths and bond angles obtained by using DFT//B3LYP/6-31G (d) method show a good agreement with the experimental data. The calculated vibrational spectra are in well agreement with the experimental one. To investigate microscopic second-order non-linear optical NLO behavior of the examined complex, the electric dipole mu, the polarizability alpha and the hyperpolarizability beta were computed using DFT//B3LYP/6-31G (d) method. The time-dependent density functional theory (TD-DFT) was employed to descript the molecular electron structure of the title compound using the B3LYP/6-31G (d) method. According to our calculations, L-histidine chloride monohydrate exhibits non-zero beta value revealing microscopic second-order NLO behavior. Copyright 2009 Elsevier B.V. All rights reserved.

  17. Crystal studies, vibrational spectra and non-linear optical properties of L-histidine chloride monohydrate

    Science.gov (United States)

    Ahmed, A. Ben; Feki, H.; Abid, Y.; Boughzala, H.; Minot, C.

    2010-01-01

    This paper presents the results of our calculations on the geometric parameters, vibrational spectra and hyperpolarizability of a non-linear optical material L-histidine chloride monohydrate. Due to the lack of sufficiently precise information on geometric parameters available in literature, theoretical calculations were preceded by re-determination of the crystal X-ray structure. Single crystal of L-histidine chloride monohydrate has been growing by slow evaporation of an aqueous solution at room temperature. The compound crystallizes in the non-Centro-symmetric space group P2 12 12 1 of orthorhombic system. IR spectrum has been recorded in the range [400-4000 cm -1]. All the experimental vibrational bands have been discussed and assigned to normal mode or to combinations on the basis of our calculations. The optimized geometric bond lengths and bond angles obtained by using DFT//B3LYP/6-31G (d) method show a good agreement with the experimental data. The calculated vibrational spectra are in well agreement with the experimental one. To investigate microscopic second-order non-linear optical NLO behavior of the examined complex, the electric dipole μ, the polarizability α and the hyperpolarizability β were computed using DFT//B3LYP/6-31G (d) method. The time-dependent density functional theory (TD-DFT) was employed to descript the molecular electron structure of the title compound using the B3LYP/6-31G (d) method. According to our calculations, L-histidine chloride monohydrate exhibits non-zero β value revealing microscopic second-order NLO behavior.

  18. The effects of creatine monohydrate supplementation with and without D-pinitol on resistance training adaptations.

    Science.gov (United States)

    Kerksick, Chad M; Wilborn, Colin D; Campbell, William I; Harvey, Travis M; Marcello, Brandon M; Roberts, Mike D; Parker, Adam G; Byars, Allyn G; Greenwood, Lori D; Almada, Anthony L; Kreider, Richard B; Greenwood, Mike

    2009-12-01

    Coingestion of D-pinitol with creatine (CR) has been reported to enhance creatine uptake. The purpose of this study was to evaluate whether adding D-pinitol to CR affects training adaptations, body composition, whole-body creatine retention, and/or blood safety markers when compared to CR ingestion alone after 4 weeks of resistance training. Twenty-four resistance trained males were randomly assigned in a double-blind manner to creatine + pinitol (CRP) or creatine monohydrate (CR) prior to beginning a supervised 4-week resistance training program. Subjects ingested a typical loading phase (i.e., 20 g/d-1 for 5 days) before ingesting 5 g/d-1 the remaining 23 days. Performance measures were assessed at baseline (T0), week 1 (T1), and week 4 (T2) and included 1 repetition maximum (1RM) bench press (BP), 1RM leg press (LP), isokinetic knee extension, and a 30-second Wingate anaerobic capacity test. Fasting blood and body composition using dual-energy x-ray absorptiometry (DEXA) were determined at T1 and T3. Data were analyzed by repeated measures analysis of variance (ANOVA). Creatine retention increased (p 0.05). Significant improvements in upper- and lower-body strength and body composition occurred in both groups. However, significantly greater increases in lean mass and fat-free mass occurred in the CR group when compared to CRP (p pinitol to creatine monohydrate does not appear to facilitate further physiological adaptations while resistance training. Creatine monohydrate supplementation helps to improve strength and body composition while resistance training. Data from this study assist in determining the potential role the addition of D-pinitol to creatine may aid in facilitating training adaptations to exercise.

  19. Evaluation of in-line spatial filter velocimetry as PAT monitoring tool for particle growth during fluid bed granulation.

    Science.gov (United States)

    Burggraeve, A; Van Den Kerkhof, T; Hellings, M; Remon, J P; Vervaet, C; De Beer, T

    2010-09-01

    In this study, the feasibility of spatial filter velocimetry (SFV) as process analytical technology tool for the in-line monitoring of the particle size distribution during top spray fluidized bed granulation was examined. The influence of several process (inlet air temperature during spraying and drying) and formulation variables (HPMC and Tween 20 concentration) upon the particle size distribution during processing, and the end product particle size distribution, tapped density and Hausner ratio was examined using a design of experiments (DOE) (2-level full factorial design, 19 experiments). The trend in end granule particle size distributions of all DOE batches measured with in-line SFV was similar to the off-line laser diffraction (LD) data. Analysis of the DOE results showed that mainly the HPMC concentration and slightly the inlet air temperature during drying had a positive effect on the average end granule size. The in-line SFV particle size data, obtained every 10s during processing, further allowed to explain and better understand the (in)significance of the studied DOE variables, which was not possible based on the LD data as this technique only supplied end granule size information. The variation in tapped density and Hausner ratio among the end granules of the different DOE batches could be explained by their difference in average end granule size. Univariate, multivariate PLS and multiway N-PLS models were built to relate these end granule properties to the in-line-measured particle size distribution. The multivariate PLS tapped density model and the multiway N-PLS Hausner ratio model showed the highest R(2) values in combination with the lowest RMSEE values (R(2) of 82% with an RMSEE of 0.0279 for tapped density and an R(2) of 52% with an RMSEE of 0.0268 for Hausner ratio, respectively). 2010 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

    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.

  1. Thermal Decomposition Kinetics of Lead 2,4,6-Trinitroresorcinate Monohydrate

    Institute of Scientific and Technical Information of China (English)

    HU Rong-zu; YAO Pu; LI Jing; CHEN San-ping; GAO Sheng-li; ZHAO Feng-qi; SONG Ji-rong; SHI Qi-zhen; CHEN Pei; LUO Yang; ZHAO Hong-an

    2004-01-01

    The non-isothermal decomposition of lead 2,4,6-trinitroresorcinate monohydrate, Pb (TNR) · H2O. was investigated by means of TG-DTA, DSC and IR. The thermal decomposition mechanism and the dissociated kinetics were also investigated. The kinetic parameters were obtained from the analysis of the DSC curves by integral and differential methods. The most probable kinetic model function of the dehydration reaction of Pb(TNR) · H2O was suggested by the comparison of the kinetic parameters.

  2. Growth kinetics of calcium oxalate monohydrate. III. Variation of solution composition

    Science.gov (United States)

    Bijvoet, Olav L. M.; Blomen, Leo J. M. J.; Will, Eric J.; van der Linden, Hanneke

    1983-11-01

    The influence of the variations of initial supersaturation, ionic strength and calcium-to-oxalate ratio on the growth kinetics of calcium oxalate monohydrate from suspension at 37°C have been investigated in an isotopic system. All experiments can be described with a single growth formula, containing three constants: kA (growth rate constant), La (thermodynamic solubility product) and [ tm] (a parameter describing the agglomeration of any seed suspension). This formula is able to predict any growth curve when the initial concentrations of seed, oxalate and indifferent electrolyte are known. Comparisons with datak from the literature are discussed.

  3. Inhibition of Monosodium Urate Monohydrate-mediated Hemolysis by Vitamin E

    Institute of Scientific and Technical Information of China (English)

    Qiong XIE; Shude LI; Weiyang FENG; Yongzhi LI; Yuanliang WU; Wei HU; Youguang HUANG

    2007-01-01

    Microcrystals of monosodium urate monohydrate (MSUM) induce cytolysis and hemolysis in erythrocytes. In this report, we studied the effect of vitamin E on MSUM-mediated hemolysis in human erythrocytes. Vitamin E significantly inhibited hemolysis induced by MSUM. The hydroxyl group in the chromanol ring of vitamin E is dispensable for protecting erythrocytes against hemolysis induced by MSUM,indicating that the inhibitory effect of vitamin E is not due to its antioxidant properties. However, both the chromanol ring and the isoprenoid side chain are important for vitamin E to suppress MSUM-induced hemolysis.Our current study suggests that vitamin E inhibits hemolysis induced by MSUM as a membrane stabilizer.

  4. In vivo comet assay of acrylonitrile, 9-aminoacridine hydrochloride monohydrate and ethanol in rats.

    Science.gov (United States)

    Nakagawa, Yuzuki; Toyoizumi, Tomoyasu; Sui, Hajime; Ohta, Ryo; Kumagai, Fumiaki; Usumi, Kenji; Saito, Yoshiaki; Yamakage, Kohji

    2015-07-01

    As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM)-initiative international validation study of the in vivo rat alkaline comet assay, we examined the ability of acrylonitrile, 9-aminoacridine hydrochloride monohydrate (9-AA), and ethanol to induce DNA damage in the liver and glandular stomach of male rats. Acrylonitrile is a genotoxic carcinogen, 9-AA is a genotoxic non-carcinogen, and ethanol is a non-genotoxic carcinogen. Positive results were obtained in the liver cells of male rats treated with known genotoxic compounds, acrylonitrile and 9-AA.

  5. First Principles Calculation of Terahertz Vibrational Modes of a Disaccharide Monohydrate Crystal of Lactose

    Science.gov (United States)

    Saito, Shigeki; Inerbaev, Talgat M.; Mizuseki, Hiroshi; Igarashi, Nobuaki; Note, Ryunosuke; Kawazoe, Yoshiyuki

    2006-11-01

    First-principles calculations of the crystalline vibrations of a lactose monohydrate crystal in the terahertz (THz) region were performed using periodic density functional theory calculations. The calculated vibrational modes in the THz region were derived from group motions with different sizes: molecules of lactose and crystal water, pyranose rings, and intramolecular frames. The intermolecular modes with large vibrational amplitude of lactose of 17.5-100.6 cm-1 and of crystal-water of 136.1-237.7 cm-1 were clearly separated. This article especially refers to the intermolecular vibrational modes of crystal water with the THz absorption, which provide detectable spectral features of hydrated crystals.

  6. The influence of crystal morphology on the kinetics of growth of calcium oxalate monohydrate

    Science.gov (United States)

    Millan, A.; Sohnel, O.; Grases, F.

    1997-08-01

    The growth of several calcium oxalate monohydrate seeds in the presence and absence of additives (phytate, EDTA and citrate) has been followed by potentiometry measurements. Growth rates have been calculated from precipitate curves by a cubic spline method and represented in logarithmic plots versus supersaturation. Crystal growth kinetics were found to be dependent on crystal morphology, crystal perfection and degree of aggregation. Some seeds were dissolving in supersaturated solutions. Other seeds showed an initial growth phase of high-order kinetics. The effect of the additives was also different on each seed. Three alternative mechanisms for calcium oxalate crystal growth are proposed.

  7. Theoretical calculation of zero field splitting parameters of Cr{sup 3+} doped ammonium oxalate monohydrate

    Energy Technology Data Exchange (ETDEWEB)

    Kripal, Ram, E-mail: ram_kripal2001@rediffmail.com; Yadav, Awadhesh Kumar, E-mail: aky.physics@gmail.com

    2015-06-15

    Zero field splitting parameters (ZFSPs) D and E of Cr{sup 3+} ion doped ammonium oxalate monohydrate (AOM) are calculated with formula using the superposition model. The theoretically calculated ZFSPs for Cr{sup 3+} in AOM crystal are compared with the experimental value obtained by electron paramagnetic resonance (EPR). Theoretical ZFSPs are in good agreement with the experimental ones. The energy band positions of optical absorption spectra of Cr{sup 3+} in AOM crystal calculated with CFA package are in good match with the experimental values.

  8. Form, formation, and deformation : the influence of material properties and process conditions on the shape of granules produced by high shear granulation

    NARCIS (Netherlands)

    Bouwman, Anneke Margriet

    2005-01-01

    High shear granulation The introduction of this thesis describes the high shear granulation process. High shear granulation is a commonly used unit operation to produce larger granules of primary particles. The granulation process has been described to consist of different stages. The initial growth

  9. Vibrational spectroscopy to support the link between rheology and continuous twin-screw melt granulation on molecular level: A case study.

    Science.gov (United States)

    Monteyne, Tinne; Heeze, Liza; Oldörp, Klaus; Vervaet, Chris; Remon, Jean-Paul; De Beer, Thomas

    2016-06-01

    Twin screw hot melt granulation (TSHMG) is an innovative and continuous drug formulation process allowing granulation of moisture sensitive drugs. However, due to the lack of experience and in-depth process understanding, this technique is not yet widely used. During the TSHMG process, the microstructure of the granules is generated and modified and strongly depends on the flow behavior of the material. Hence, rheology might be a suitable tool to simulate and examine this process. However, chemical interactions of the material are influencing the physical properties leading to the microstructure. In this research project it is spectroscopically investigated whether the heat applied in a rheometer induces the same molecular effects as these occurring during TSHMG of the model formulation caffeine anhydrous/Soluplus®. Hence, it is evaluated whether rheology can be used as a simulation tool to improve the understanding of the material behavior at molecular level during continuous melt granulation. Therefore, in-line Raman spectroscopy is executed during TSHMG and in situ Fourier Transform Infra-red (FTIR) during oscillatory rheological experiments. The results from the in-line Raman monitoring revealed polymorph transition of caffeine anhydrous during twin screw melt granulation with Soluplus® which is stimulated depending on the binder concentration and/or granulation temperature. A correlation was seen between the FTIR spectra obtained during the rheological temperature ramp and the in-line collected Raman spectra during the melt granulation runs. The polymorphic conversion of caffeine anhydrous could be detected in the same temperature range with both techniques, proving the comparability of plate-plate rheometry and hot melt granulation (HMG) for this case with the used parameter settings. Process simulation using rheology combined with in situ FTIR seems a promising approach to increase process understanding and to facilitate binder and parameter selection for

  10. Implementation of an artificial neural network as a PAT tool for the prediction of temperature distribution within a pharmaceutical fluidized bed granulator.

    Science.gov (United States)

    Korteby, Yasmine; Mahdi, Yassine; Azizou, Amel; Daoud, Kamel; Regdon, Géza

    2016-06-10

    In this study, a novel in-line measurement technique of the air temperature distribution during a granulation process using a conical fluidized bed was designed and built for the purpose of measuring the temperature under the Process Analytical Technology (PAT) and introduced to predict the establishment of temperature profiles. Three sets of thermocouples were used, placed at different positions covering the whole operating range, connected to data acquisition measurement hardware, allowing an in-line acquisition and recording of temperatures every second. The measurements throughout the fluidized bed were performed in a steady state by spraying a solution of PVP onto a lactose monohydrate powder bed in order to make predictions of the temperature distribution and the hydrodynamics of the bed during the granulation process using Artificial Neural Networks (ANNs) and to establish the different temperature profiles for different process conditions through the precise predicted information by the constructed, trained, validated and tested neural network. The model's testing results showed a strong prediction capacity of the effects of process variables. Indeed, the predicted temperature values obtained with the ANN model were in good agreement with the values measured with in-line reference method and hence the method can have an application as a predictive control tool.

  11. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this arch

  12. IT Supporting Strategy Formulation

    NARCIS (Netherlands)

    Achterbergh, J.M.I.M.

    2005-01-01

    This overview approaches information and communication technology (ICT) for competitive intelligence from the perspective of strategy formulation. It provides an ICT architecture for supporting the knowledge processes producing relevant knowledge for strategy formulation. To determine what this arch

  13. Protein Methylation and Stress Granules: Posttranslational Remodeler or Innocent Bystander?

    Directory of Open Access Journals (Sweden)

    Wen Xie

    2011-01-01

    Full Text Available Stress granules contain a large number of post-translationally modified proteins, and studies have shown that these modifications serve as recruitment tags for specific proteins and even control the assembly and disassembly of the granules themselves. Work originating from our laboratory has focused on the role protein methylation plays in stress granule composition and function. We have demonstrated that both asymmetrically and symmetrically dimethylated proteins are core constituents of stress granules, and we have endeavored to understand when and how this occurs. Here we seek to integrate this data into a framework consisting of the currently known post-translational modifications affecting stress granules to produce a model of stress granule dynamics that, in turn, may serve as a benchmark for understanding and predicting how post-translational modifications regulate other granule types.

  14. Enhanced aerobic nitrifying granulation by static magnetic field.

    Science.gov (United States)

    Wang, Xin-Hua; Diao, Mu-He; Yang, Ying; Shi, Yi-Jing; Gao, Ming-Ming; Wang, Shu-Guang

    2012-04-01

    One of the main challenging issues for aerobic nitrifying granules in treating high strength ammonia wastewater is the long granulation time required for activated sludge to transform into aerobic granules. The present study provides a novel strategy for enhancing aerobic nitrifying granulation by applying an intensity of 48.0mT static magnetic field. The element analysis showed that the applied magnetic field could promote the accumulation of iron compounds in the sludge. And then the aggregation of iron decreased the full granulation time from 41 to 25days by enhancing the setting properties of granules and stimulating the secretion of extracellular polymeric substances (EPS). Long-term, cycle experiments and fluorescence in-situ hybridization (FISH) analysis proved that an intensity of 48.0mT magnetic field could enhance the activities and growth of nitrite-oxidizing bacteria (NOB). These findings suggest that magnetic field is helpful and reliable for accelerating the aerobic nitrifying granulation.

  15. Torsion formulation of gravity

    Energy Technology Data Exchange (ETDEWEB)

    Lledo, M A; Sommovigo, L, E-mail: Maria.Lledo@ific.uv.e, E-mail: Luca.Sommovigo@mfn.unipmn.i [Departament de Fisica Teorica, Universitat de Valencia, and IFIC (Centro mixto CSIC-UVEG) C/Dr Moliner, 50, E-46100 Burjassot (Valencia) (Spain)

    2010-03-21

    We explain precisely what it means to have a connection with torsion as a solution of the Einstein equations. While locally the theory remains the same, the new formulation allows for topologies that would have been excluded in the standard formulation of gravity. In this formulation it is possible to couple arbitrary torsion to gauge fields without breaking the gauge invariance.

  16. Hemoglobin expression in rat experimental granulation tissue

    Institute of Scientific and Technical Information of China (English)

    Miretta Tommila; Christoffer Stark; Anne Jokilammi; Ville Peltonen; Risto Penttinen; Erika Ekholm

    2011-01-01

    The general opinion that hemoglobin is only a carrier protein for oxygen and carbon dioxide has been challenged by several recent studies showing hemoglobin expression in other cells than those of the erythroid series, for example, in macrophages. We discovered β-globin expression in rat experimental granulation tissue induced by subcutaneously implanted cellulose sponges. Closer investigation revealed also α-globin expression. The first peak of the biphasic globin expression noticed during granulation tissue formation correlated with the invasion of monocytes/macrophages, whereas the second one seemed to be connected to the appearance of hematopoietic progenitors. Data presented in this study indicate globin expression both in macrophages and in immature erythroid cells as validated by erythroid-specific markers.

  17. The morphological details of globular keratohyalin granules.

    Science.gov (United States)

    Westerhof, W; Dingemans, K P

    1986-10-01

    In quickly dividing epithelia such as that of the tongue, keratohyalin formation takes place in globular keratohyalin granules (KHG). This is in contrast with the irregular KHG as seen in normal, slowly dividing epidermis. The morphogenesis of the globular KHG is explained in this study. In small KHG, dense aggregates of ribosomes can be seen at the site of blebs. It is suggested that these blebs framed with ribosomes are internalized giving rise to "dense homogeneous deposits" or "single granules". Lipid droplets occur in the upper spinous and horny layer. Globular KHG also contain variable amounts of lipids, and the lipid content seems to be inversely related to the protein content, dependent on the degree of cell differentiation or on the rate of cell turnover. It is suggested that in epithelia with a high cell turnover few rigid keratohyalin components are dispersed in lipids, which maintain a globular shape due to the surface tension.

  18. Zymophagy: Selective Autophagy of Secretory Granules

    Directory of Open Access Journals (Sweden)

    Maria I. Vaccaro

    2012-01-01

    Full Text Available Timing is everything. That's especially true when it comes to the activation of enzymes created by the pancreas to break down food. Pancreatic enzymes are packed in secretory granules as precursor molecules called zymogens. In physiological conditions, those zymogens are activated only when they reach the gut, where they get to work releasing and distributing nutrients that we need to survive. If this process fails and the enzymes are prematurely activated within the pancreatic cell, before they are released from the gland, they break down the pancreas itself causing acute pancreatitis. This is a painful disease that ranges from a mild and autolimited process to a severe and lethal condition. Recently, we demonstrated that the pancreatic acinar cell is able to switch on a refined mechanism that could explain the autolimited form of the disease. This is a novel selective form of autophagy named zymophagy, a cellular process to specifically detect and degrade secretory granules containing activated enzymes before they can digest the organ. In this work, we revise the molecules and mechanisms that mediate zymophagy, a selective autophagy of secretory granules.

  19. CARBOCYSTEINE LYSINE SALT MONOHYDRATE IN TREATMENT OF DISEASES OF LOWER RESPIRATORY TRACT IN CHILDREN

    Directory of Open Access Journals (Sweden)

    T. A. Kruchkova

    2013-01-01

    Full Text Available Inflammatory diseases of the respiratory tract are characterized by changes in rheological properties of the phlegm and lower of the mucociliary clearance. Adjustment of mucoregulatory agents is of a special significance in treatment of diseases of the lower respiratory tract in children. Aim: to assess efficacy of carbocysteine lysine salt monohydrate as a mucokinetic agent in children with respiratory tract diseases. Patients and methods: 65 children (31 girls and 34 boys aged from 5 to 16 years old with acute respiratory tract diseases received treatment in Belgorod pediatric out-patient clinic № 4 were included into the study. The results of the clinical follow-up of these children are shown in the article. Results: carbocysteine lysine salt monohydrate was found to be effective and safe in treatment of acute and chronic inflammatory diseases of the respiratory tract in children. The authors observed quicker convalescence of the patients and possibility of combination of this drug with other medicines used in pediatric practice. Conclusions: the above-mentioned drug when used in combination with antibacterial agents intensifies penetration of the latter into the bronchial secretion and bronchial mucous membrane thereby increasing their efficacy. The drug does not have toxicity, is well-tolerated even when prolonged using and can be recommended for treatment of cough in children both under out- and in-patients conditions.Keywords: children, respiratory tract diseases, carbocysteine.

  20. Influence of binder droplet dimension on granulation rate during fluidized bed granulation.

    Science.gov (United States)

    Fujiwara, Maya; Dohi, Masafumi; Otsuka, Tomoko; Yamashita, Kazunari; Sako, Kazuhiro

    2013-01-01

    Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.

  1. Identification of Polymorphic Forms of Active Pharmaceutical Ingredient in Low-Concentration Dry Powder Formulations by Synchrotron X-Ray Powder Diffraction.

    Science.gov (United States)

    Egusa, Kenji; Okazaki, Fumiaki; Schiewe, Joerg; Werthmann, Ulrike; Wolkenhauer, Markus

    2017-09-13

    The identification of different (pseudo) polymorphs of an active pharmaceutical ingredient in dry powder formulations is of importance during development and entire product lifecycle, e.g., quality control. Whereas determination of polymorphic differences of pure substances is rather easy, in dry powder formulations, it is generally difficult and the difficulties increase particularly, if the substance of interest is present only in low concentrations in the formulation. Such a formulation is Spiriva(®) inhalation powder (Boehringer Ingelheim), which contains only 0.4 w/w% of the active pharmaceutical ingredient tiotropium bromide monohydrate in a matrix of α-lactose monohydrate as excipient. In this study, identification of 0.4 w/w% tiotropium bromide in the dry powder formulation was examined by X-ray powder diffraction (XRPD) using a synchrotron radiation source and the results were compared with the conventional laboratory XRPD measurements. The detection limit of tiotropium bromide by the laboratory XRPD was around 2-5 w/w%, and hence, detection of 0.4 w/w% tiotropium bromide was impossible. The synchrotron XRPD was capable to detect significantly lower level of tiotropium bromide by at least an order of magnitude. Four different polymorphic forms of tiotropium bromide present at 0.4 w/w% concentration in lactose powder blends were unambiguously identified by the synchrotron XRPD method.

  2. Managing and Monitoring of Aspergillus flavus in Corn Using Bioplastic-based Formulation

    Science.gov (United States)

    In this study, we evaluated the feasibility of bioplastic-based formulations for delivering a non-aflatoxigenic strain of Aspergillus flavus and for monitoring Aspergilli with the final objective of controlling aflatoxin contamination in corn. Field application of inoculated bioplastic granules show...

  3. Efficacy of water dispersible formulations of biocontrol strains of Aspergillus flavus for aflatoxin management in corn

    Science.gov (United States)

    Field experiments were conducted in 2011 and 2012 to evaluate the efficacy of water dispersible granule (WDG) formulations of biocontrol strains of Aspergillus flavus in controlling aflatoxin contamination of corn. In 2011, when aflatoxin was present at very high levels, no WDG treatment provided s...

  4. Compatibility of cholecalciferol, haloperidol, imipramine hydrochloride, levodopa/carbidopa, lorazepam, minocycline hydrochloride, tacrolimus monohydrate, terbinafine, tramadol hydrochloride and valsartan in SyrSpend SF PH4 oral suspensions.

    Science.gov (United States)

    Polonini, H C; Silva, S L; Cunha, C N; Brandão, M A F; Ferreira, A O

    2016-04-01

    A challenge with compounding oral liquid formulations is the limited availability of data to support the physical, chemical and microbiological stability of the formulation. This poses a patient safety concern and a risk for medication errors. The objective of this study was to evaluate the compatibility of the following active pharmaceutical ingredients (APIs) in 10 oral suspensions, using SyrSpend SF PH4 (liquid) as the suspending vehicle: cholecalciferol 50,000 IU/mL, haloperidol 0.5 mg/mL, imipramine hydrochloride 5.0 mg/mL, levodopa/carbidopa 5.0/1.25 mg/mL, lorazepam 1.0 mg/mL, minocycline hydrochloride 10.0 mg/mL, tacrolimus monohydrate 1.0 mg/mL, terbinafine 25.0 mg/mL, tramadol hydrochloride 10.0 mg/mL and valsartan 4.0 mg/mL. The suspensions were stored both refrigerated (2 - 8 degrees C) and at controlled room temperature (20 - 25 degrees C). This is the first stability study for these APIs in SyrSpend SF PH4 (liquid). Further, the stability of haloperidol,ilmipramine hydrochloride, minocycline, and valsartan in oral suspension has not been previously reported in the literature. Compatibility was assessed by measuring percent recovery at varying time points throughout a 90 days period. Quantification of the APIs was performed by high performance liquid chromatography (HPLC-UV). Given the percentage of recovery of the APIs within the suspensions, the beyond-use date of the final preparations was found to be at least 90 days for most suspensions both refrigerated and at room temperature. Exceptions were: Minocycline hydrochloride at both storage temperatures (60 days), levodopa/carbidopa at room temperature (30 days), and lorazepam at room temperature (60 days). This suggests that compounded suspensions of APIs from different pharmacological classes in SyrSpend SF PH4 (liquid) are stable.

  5. WET-GRANULATION RESEARCH WITH APPLICATION TO SCALE-UP

    Institute of Scientific and Technical Information of China (English)

    Gabriel I.Tardos

    2005-01-01

    Granulation is a unit operation by which larger granules are produced from fine, powdery particles to improve appearance, flow properties and mixedness, reduce dustiness and, in general, produce engineered particles with superior attributes. Agglomeration in wet granulation is achieved by introducing a "binder" fluid onto a shearing mass of fine powders. This paper gives a general overview of the process with emphasis on a simplified granulation model based on a dimensionless parameter containing inertia and viscous dissipation energies between colliding particles: the so-called Stokes number. The model incorporates most common features of all granulation devices (mixers) used in the pharmaceutical industry.Also described in the paper is a computer simulation that captures the movement of flowing powder in an ideal mixer-granulator with constant shear rate. A fraction of the total number of particles is wet (covered by binder and therefore "sticky") while the rest of the particles are dry. The numerical simulation depicts two distinct regimes of agglomeration found in a typical granulator: granule growth and subsequent breakup. During granule growth-simulations, final granule size and shape distributions are obtained by analyzing the size and shape of formed granules using a pattern-recognition technique. A second kind of simulation, also using rapid granular flow modeling, follows the rotation and deformation of an "agglomerate" held together by a liquid binder. Results from these simulations yield critical values of the Stokes number. Below the critical value, the agglomerates are stable and only rotate in response to shear while above the critical value they break into two or more pieces. At the critical value, they attain a steady elongated shape. Using values of the critical Stokes number, the model predicts the size of formed granules.The existence of the critical state in which granules attain a characteristic elongated shape is used to measure shear forces

  6. Formation of artificial granules for proving gelation as the main mechanism of aerobic granulation in biological wastewater treatment.

    Science.gov (United States)

    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.

  7. KEKUATAN GEL GELATIN TIPE B DALAM FORMULASI GRANUL TERHADAP KEMAMPUAN MUKOADHESIF

    Directory of Open Access Journals (Sweden)

    Astri Fajriani

    2009-06-01

    Full Text Available Type B Gelatin Gel Strength in Granule Formulation and its Mucoadhesive Characteristics. Mucoadhesive test of polymer excipient is important for development of oral sustained release dosage form in mucoadhesive system to increase bioavailability of a drug. The study focused on mucoadhesive strength of gelatinus granules in stomach and intestine of rat using bioadhesive and wash off tests. Gelatin is a substance obtained from partially hydrolyzed collagen of skin, white cattle bones and animal bones. Gelatin derived from acid process is called type A gelatin and those from alkali process is called type B gelatin. This research studied the influence of various gel strength of type B gelatins, particularly their mucoadhesive characteristics. Mucoadhesive tests were performed at the concentration of 7.14%, 3.66%, and 2.45% and with gel strength of 328 g Bloom, 230 g Bloom and 119 g Bloom respectively. The results showed that granules formula with 230 g Bloom gel strength showed the best mucoadhesive strength, with adhesion percentage of 100%.

  8. Formulation andin-vitro preliminary screening of polyphyto antilithiatic combination

    Institute of Scientific and Technical Information of China (English)

    Abhishek Bharadwaj; Kumud Upadhayaya; N V Satheesh Madhav

    2013-01-01

    Objective:To study people suffered from urinary stone problem by calcium oxalate monohydrate (COM) and calcium oxalate dihydrate(COD) containing stones.Method:In the present study,CO crystals were grown by mixing and stirring two equal volumes of solutionsA andB.Two solutions of following composition were mixed:A:Na2C2O4(2 mmol) andB:CaCl2.2H2O(10 mmol).The crystals after incubation in tris buffer were then subjected to the aqueous extract of the polyherbal formulation and cystone was taken as standard.Result:After the treatment with the extract the crystals were microscopically examined and elemental analysis for calcium was carried out.The formulation proved out to be very effective against theCO crystals.Conclusions:The results have come out to be very motivating and further pharmacological study could be carried out on the samples to reveal an effective drug for the urolithiasis.Data reveals that phytotherapeutic agents could be useful as either an alternative or a complementary therapy in the management of urolithiasis.

  9. Bone regeneration in rabbit calvaria with novel monetite granules.

    Science.gov (United States)

    Tamimi, Faleh; Torres, Jesús; Kathan, Carlos; Baca, Rafael; Clemente, Celia; Blanco, Luis; Lopez Cabarcos, Enrique

    2008-12-15

    The aim of this study was to evaluate whether local application of monetite granules would induce bone regeneration in critical size defects on rabbits calvaria. Novel monetite granules were synthesized by thermal conversion of preset brushite cement. Twelve female New Zealand rabbits were used for this study. Two identical 10-mm-diameter bicortical cranial defects were created in each animal. One of the defects was grafted with monetite granules while the contralateral was left unfilled as negative control. Animals were sacrificed at 4 and 8 weeks after surgery, and biopsies were taken for histological and histomorphometrical evaluation under light microscopy. Wilcoxon test was used for statistical analysis. The histological observations showed signs of graft resorption as newly formed bone tissue grew surrounding and penetrating the monetite granules. Histomorphometric evaluation showed that the augmented bone volume as well as the augmented mineral tissue was higher in the defects treated with monetite granules (p monetite granules in bone defects enhances bone healing significantly.

  10. Information granules and entropy theory in information systems

    Institute of Scientific and Technical Information of China (English)

    LIANG JiYe; QIAN YuHua

    2008-01-01

    Information granulation and entropy theory are two main approaches to research uncertainty of an information system,which have been widely applied in many practical issues.In this paper,the characterizations and representations of information granules under various binary relations are investigated in information systems,an axiom definition of information granulation is presented,and some existing definitions of information granulation become its special forms.Entropy theory in information systems is further developed and the granulation monotonicity of each of them is proved.Moreover,the complement relationship between information granulation and entropy is established.This investigation unifies the results of measures for uncertainties in complete information systems and incomplete information systems.

  11. Giant arachnoid granulation in a patient with benign intracranial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat [Pamukkale University, Department of Radiology, School of Medicine, Denizli (Turkey)

    2008-10-15

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  12. Three-dimensional arrangement of β-tricalcium phosphate granules evaluated by microcomputed tomography and fractal analysis.

    Science.gov (United States)

    Ndiaye, Mambaye; Terranova, Lisa; Mallet, Romain; Mabilleau, Guillaume; Chappard, Daniel

    2015-01-01

    The macrophysical properties of granular biomaterials used to fill bone defects have rarely been considered. Granules of a given biomaterial occupy three-dimensional (3-D) space when packed together and create a macroporosity suitable for the invasion of vascular and bone cells. Granules of β-tricalcium phosphate were prepared using polyurethane foam technology and increasing the amount of material powder in the slurry (10, 11, 15, 18, 21 and 25 g). After sintering, granules of 1000-2000 μm were prepared by sieving. They were analyzed morphologically by scanning electron microscopy and placed in polyethylene test tubes to produce 3-D scaffolds. Microcomputed tomography (microCT) was used to image the scaffolds and to determine porosity and fractal dimension in three dimensions. Two-dimensional sections of the microCT models were binarized and used to compute classical morphometric parameters describing porosity (interconnectivity index, strut analysis and star volumes) and fractal dimensions. In addition, two newly important fractal parameters (lacunarity and succolarity) were measured. Compression analysis of the stacks of granules was done. Porosity decreased as the amount of material in the slurry increased but non-linear relationships were observed between microarchitectural parameters describing the pores and porosity. Lacunarity increased in the series of granules but succolarity (reflecting the penetration of a fluid) was maximal in the 15-18 g groups and decreased noticeably in the 25 g group. The 3-D arrangement of biomaterial granules studied by these new fractal techniques allows the optimal formulation to be derived based on the lowest amount of material, suitable mechanical resistance during crushing and the creation of large interconnected pores. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  13. Explosive Formulation Pilot Plant

    Data.gov (United States)

    Federal Laboratory Consortium — The Pilot Plant for Explosive Formulation supports the development of new explosives that are comprised of several components. This system is particularly beneficial...

  14. Effects of monohydric alcohols and polyols on the thermal stability of a protein

    Science.gov (United States)

    Murakami, Shota; Kinoshita, Masahiro

    2016-03-01

    The thermal stability of a protein is lowered by the addition of a monohydric alcohol, and this effect becomes larger as the size of hydrophobic group in an alcohol molecule increases. By contrast, it is enhanced by the addition of a polyol possessing two or more hydroxyl groups per molecule, and this effect becomes larger as the number of hydroxyl groups increases. Here, we show that all of these experimental observations can be reproduced even in a quantitative sense by rigid-body models focused on the entropic effect originating from the translational displacement of solvent molecules. The solvent is either pure water or water-cosolvent solution. Three monohydric alcohols and five polyols are considered as cosolvents. In the rigid-body models, a protein is a fused hard spheres accounting for the polyatomic structure in the atomic detail, and the solvent is formed by hard spheres or a binary mixture of hard spheres with different diameters. The effective diameter of cosolvent molecules and the packing fractions of water and cosolvent, which are crucially important parameters, are carefully estimated using the experimental data of properties such as the density of solid crystal of cosolvent, parameters in the pertinent cosolvent-cosolvent interaction potential, and density of water-cosolvent solution. We employ the morphometric approach combined with the integral equation theory, which is best suited to the physical interpretation of the calculation result. It is argued that the degree of solvent crowding in the bulk is the key factor. When it is made more serious by the cosolvent addition, the solvent-entropy gain upon protein folding is magnified, leading to the enhanced thermal stability. When it is made less serious, the opposite is true. The mechanism of the effects of monohydric alcohols and polyols is physically the same as that of sugars. However, when the rigid-body models are employed for the effect of urea, its addition is predicted to enhance the

  15. Freeze granulation for the processing of silicon nitride ceramics

    Energy Technology Data Exchange (ETDEWEB)

    Lyckfeldt, O. [Swedish Ceramic Inst., Goeteborg (Sweden); Rundgren, K. [Permascand AB, Ljungaverk (Sweden); Sjoestedt, M. [PowderPro HB, Hisings Backa (Sweden)

    2004-07-01

    Freeze granulation (LS-2, PowderPro HB, Sweden) has been demonstrated as a favourable alternative to conventional granulation methods (spray drying, sieve granulation etc) in the production of granules for the pressing of high-performance ceramic powders. Freeze granulation/freeze drying prevents the migration of pressing aids or particle fines to the granule surface, as is the case in spray drying. This ensures granule homogeneity and an easy breakdown of granules during pressing. This, in turn, results in defect minimisation and optimal conditions for the sintering and the development of the desired material properties. In this study silicon nitride materials have been produced using freeze granulation, pressing and sintering to validate the performance. Materials with competitive properties were manufactured based on medium-cost, direct-nitrided powders (SicoNide P95, Permascand AB, Sweden), various pressing and sintering aid compositions as well as various pressing and sintering schedules. MgO vs Fe{sub 2}O{sub 3} as sintering aid, PEG vs PVA as binder and higher pressure at the initial uniaxial pressing were found to promote the sintering performance. (orig.)

  16. Application of the Molecular Combing Technique to Starch Granules

    Directory of Open Access Journals (Sweden)

    Zhong-Dong Liu

    2009-10-01

    Full Text Available The molecular combing technique was used to dissociate the nanostructural units of starch granules from the starch fragments after a gelatinization process. With the help of atomic force microscopy (AFM, we observed that some nanostructural chains were just flowing out of the granules. It proves that there are substantive nanostructural units in the starch granules, a phenomenon not previously observed, so these nanostructural units were defined as suspected intermediates. Furthermore, we conclude that blocklets of starch granules are formed through twisting or distortion of nanochains.

  17. CHARACTERIZATION AND ADSORPTION PROPERTIES OF POROUS CARBON NANOFIBER GRANULES

    Institute of Scientific and Technical Information of China (English)

    Jiuling Chen; Qinghai Chen; Yongdan Li

    2006-01-01

    The properties of the porous granules produced by agglomeration of catalytically grown carbon nanofibers were investigated in this work. The single pellet crushing strength of the granules is high, e.g., 1.6-2.5 MPa. They have adsorption at 298 K of benzene or phenol on the granules is much lower than that on activated carbon and depends not only on the specific surface area of the carbon material but also on the sewing structure of the granules and the morphology of the carbon nanofibers. Treatment in dilute nitric acid appreciably reduces such adsorption.

  18. Aerobic granulation of pure bacterial strain Bacillus thuringiensis

    Institute of Scientific and Technical Information of China (English)

    Sunil S ADAV; Duu-Jong LEE

    2008-01-01

    The objective of this study is to cultivate aer-obic granules by pure bacterial strain, Bacillus thuringien-sis, in a sequencing batch reactor. Stable granules sized 2.0-2.2 mm were formed in the reactor after a five-week cultivation. These granules exhibited excellent settling attributes, and degraded phenol at rates of 1.49 and concentration, respectively. Confocal laser scanning microscopic test results show that Bacillus thuringiensis was distributed over the initial small aggregates, and the outer edge of the granule was away from the core regime in the following stage.

  19. Osseointegration of alumina bioceramic granules: A comparative experimental study

    Science.gov (United States)

    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.

  20. Microbial granulation for lactic acid production.

    Science.gov (United States)

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon; Im, Wan-Taek; Yun, Yeo-Myeong; Park, Chul; Kim, Mi-Sun

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which was fed with 2% glucose and operated at a hydraulic retention time (HRT) of 12 h and pH 5.0 ± 0.1 under a thermophilic condition (50°C). The mixed liquor in the CSTR was then transferred to an up-flow anaerobic sludge blanket reactor (UASB). The fermentation performance and granulation process were monitored with a gradual decrease of HRT from 8.0 to 0.17 h, corresponding to an increase in the substrate loading from 60 to 2,880 g glucose L(-1) d(-1) . As the operation continued, the accumulation of biomass in the UASB was clearly observed, which changed from flocculent to granular form with decrease in HRT. Up to the HRT decrease to 0.5 h, the LA concentration was maintained at 19-20 g L(-1) with over 90% of substrate removal efficiency. However, further decrease of HRT resulted in a decrease of LA concentration with increase in residual glucose. Nevertheless, the volumetric LA productivity continuously increased, reaching 67 g L-fermenter (-1) h(-1) at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s(-1) and 0.39-0.92, respectively. © 2015 Wiley Periodicals, Inc.

  1. FORMULATION AND DISSOLUTION STUDY OF DILTIAZEM HYDROCHLORIDE IMMEDIATE RELEASE TABLETS

    Directory of Open Access Journals (Sweden)

    BRAHMAIAH BONTHAGARALA

    2014-08-01

    Full Text Available Objective: The main aim and objective of the work is to formulate immediate release tablets using different direct compression vehicles (DCV’S in different ratios. Methods: In the present study, design of oral immediate release tablets of Diltiazem hydrochloride by direct compression technique was carried out. Results: The main motive is to compare the dissolution profile of these formulations and conclude the best formulation which release drug at a faster rate . To determine the best fit dissolution profile for the dosage forms. Diltiazem hydrochloride tablets were formulated by using microcrystalline cellulose (diluent, potato starch, acacia (binder and magnesium stearate (lubricant. The granules were compressed into tablets and were subjected to dissolution studies. The dissolution profile of the formulation F2 was found to have better dissolution rate compared to others. Conclusion: The Invitro dissolution studies of all the formulations were conducted and the results were obtained, it was concluded that formulation F2 was the best with fast release of drug compared to others.

  2. Characterisation of Organomineral Fertilisers Derived from Nutrient-Enriched Biosolids Granules

    Directory of Open Access Journals (Sweden)

    Diogenes L. Antille

    2013-01-01

    Full Text Available Organomineral fertilisers (OMFs were produced by coating biosolids granules with urea and potash. Two OMF formulations with N : P2O5 : K2O compositions: 10 : 4 : 4 (OMF10 and 15 : 4 : 4 (OMF15 were developed for application in grassland and arable crops. Routine fertiliser analyses were conducted on four batches of OMF and biosolids granules and compared with a sample of urea to determine key physical and chemical properties of the materials which affect handling and spreading, soil behaviour, and fertiliser value. Bulk and particle densities were in the range of 608 to 618 kg m−3, and 1297 to 1357 kg m−3, respectively. Compression tests showed that OMF particles undergo deformation followed by multiple failures without disintegration of the granules when vertical load was applied. Static particle strength was between 1.18 and 4.33 N mm−2 depending on the particle diameter. The use of a model for fertiliser particle distribution studies showed that OMF granules should be between 1.10 and 5.50 mm in diameter with about 80% of the particles in the range of 2.25 to 4.40 mm to enable application at 18 m tramline spacing. This research utilises novel technology to improve the fertiliser value of biosolids, reduce disposal costs, and deliver a range of environmental benefits associated with recycling.

  3. Observation of polyphosphate granules in cable bacteria

    Science.gov (United States)

    Yang, T.; Nielsen, L. P.; Risgaard-Petersen, N.

    2015-12-01

    Cable bacteria are long filamentous bacteria that capable for long distance electron transport: transporting electrons derived from oxidizing sulfide in anoxic layers, to oxygen at the sediment surface, over a distance of centimeters. Cable bacteria are found in many types of freshwater and marine sediment all over the world, with density of approximately thousands of kilometers per square meter. These long filaments are composed by individual cells closely related to Desulfobulbaceae, connected with a shared outer membrane inside which the strings structure are presumed to be highly conductive. The observed doubling time of cells within the filament is about 20 min, which is among the shortest compare to other bacteria. In these cable cells, we constantly observed polyphosphate granules (poly-P), regardless of cell dimension and shape. This is very interesting since it has long been recognized that the microbial polyP content is low during rapid growth and increases under unfavorable conditions, for example, increasing sulfide concentration and anoxia resulted in a decomposition of poly-P in Beggiatoa. Here, we investigated marine cable bacteria from Netherland and Aarhus Bay, focusing on the poly-P dynamics under various redox conditions. In poly-P stained cells, typically there are two big poly-P granules locate at each polar. In dividing cells, however, the morphology of poly-P changed to six small granules precisely arranged to two row. Moreover, the cells seem be able to continuously divide more than one time without elongation step. These varied poly-P morphologies demonstrate that poly-P is closely related to the cell growth and cell division, by an unknown mechanism. Individual cable filaments were picked up and were exposed to different redox conditions; our primary data indicated the cable cells could suffer anoxic condition better than oxic condition. We also detected decomposition of poly-P under anoxia. These results call for an in-depth examination

  4. In planta modification of potato starch granule biogenesis by different granule-bound fusion proteins

    NARCIS (Netherlands)

    Nazarian, F.

    2007-01-01

    Starch is composed of amylose and amylopectin and it is deposited in amyloplasts/choloroplasts as semi-crystalline granules. Many biosynthetic enzymes are involved in starch degradation and biosynthesis. Some microbial starch degrading enzymes have a Starch Binding Domain (SBD) which has affinity fo

  5. A comparative study between melt granulation/compression and hot melt extrusion/injection molding for the manufacturing of oral sustained release thermoplastic polyurethane matrices.

    Science.gov (United States)

    Verstraete, G; Mertens, P; Grymonpré, W; Van Bockstal, P J; De Beer, T; Boone, M N; Van Hoorebeke, L; Remon, J P; Vervaet, C

    2016-11-20

    During this project 3 techniques (twin screw melt granulation/compression (TSMG), hot melt extrusion (HME) and injection molding (IM)) were evaluated for the manufacturing of thermoplastic polyurethane (TPU)-based oral sustained release matrices, containing a high dose of the highly soluble metformin hydrochloride. Whereas formulations with a drug load between 0 and 70% (w/w) could be processed via HME/(IM), the drug content of granules prepared via melt granulation could only be varied between 85 and 90% (w/w) as these formulations contained the proper concentration of binder (i.e. TPU) to obtain a good size distribution of the granules. While release from HME matrices and IM tablets could be sustained over 24h, release from the TPU-based TSMG tablets was too fast (complete release within about 6h) linked to their higher drug load and porosity. By mixing hydrophilic and hydrophobic TPUs the in vitro release kinetics of both formulations could be adjusted: a higher content of hydrophobic TPU was correlated with a slower release rate. Although mini-matrices showed faster release kinetics than IM tablets, this observation was successfully countered by changing the hydrophobic/hydrophilic TPU ratio. In vivo experiments via oral administration to dogs confirmed the versatile potential of the TPU platform as intermediate-strong and low-intermediate sustained characteristics were obtained for the IM tablets and HME mini-matrices, respectively.

  6. Pharmacokinetics and bioequivalence testing of five commercial formulations of omeprazole in the horse.

    Science.gov (United States)

    Sykes, B W; Underwood, C; Greer, R; McGowan, C M; Mills, P C

    2016-02-01

    Omeprazole is widely used in the treatment of equine gastric ulcer syndrome. To date, little is known about the relative pharmacokinetics of the different formulations making comparisons between products difficult. The objectives of the study were to investigate the relative pharmacokinetics of five commercially available formulations of omeprazole in the horse and to test for bioequivalence of four of the formulations using one of the formulations as a reference standard. Twelve mature Thoroughbred horses were fasted for 16 h then administered 2 g of each formulation in a cross-over design. Serial blood samples were collected and plasma omeprazole concentration was determined by ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS). No significant differences were present between three of the formulations and the reference formulation, while the fourth formulation had a lower Cmax and longer Tmax than the reference formulation. Bioequivalence against the reference formulation could not be demonstrated for any of the formulations tested. The findings of the study suggested that the method of protection utilised by different formulations of omeprazole (enteric-coated granules vs. buffering) does not significantly alter the pharmacokinetics of the drug. Further work to establish bioequivalence is needed before direct comparisons can be drawn between different formulations.

  7. EPR and optical absorption studies of Cr3+ ions in d-gluconic acid monohydrate.

    Science.gov (United States)

    Kripal, Ram; Singh, Pragya; Govind, Har

    2009-10-01

    EPR studies are carried out on Cr(3+) ions doped in d-gluconic acid monohydrate (C(6)H(12)O(7)*H(2)O) single crystals at 77 K. From the observed EPR spectra, the spin Hamiltonian parameters g, |D| and |E| are measured to be 1.9919, 349 (x 10(-4)) cm(-1) and 113 (x 10(-4)) cm(-1), respectively. The optical absorption of the crystal is also studied at room temperature. From the observed band positions, the cubic crystal field splitting parameter Dq (2052 cm(-1)) and the Racah interelectronic repulsion parameter B (653 cm(-1)) are evaluated. From the correlation of EPR and optical data the nature of bonding of Cr(3+) ion with its ligands is discussed.

  8. 1,3-Dicyclohexyl-3-[(pyridin-2-ylcarbonyl]urea monohydrate from synchrotron radiation

    Directory of Open Access Journals (Sweden)

    Solange M. S. V. Wardell

    2011-10-01

    Full Text Available The title urea derivative crystallizes as a monohydrate, C19H27N3O2·H2O. The central C3N grouping is almost planar (r.m.s. deviation = 0.0092 Å, and the amide and pyridine groups are substantially twisted out this plane [dihedral angles = 62.80 (12 and 34.98 (10°, respectively]. Supramolecular double chains propagating along the b-axis direction feature in the crystal packing whereby linear chains sustained by N—H...O hydrogen bonds formed between the amide groups are linked by helical chains of water molecules (linked by O—H...O hydrogen bonds. The H atom that participates in these water chains is disordered over two positions of equal occupancy. The double chains are connected into a two-dimensional array by C—H...O contacts and the layers stack along the a axis.

  9. Crystal structure of potassium (1S-d-lyxit-1-ylsulfonate monohydrate

    Directory of Open Access Journals (Sweden)

    Alan H. Haines

    2015-08-01

    Full Text Available The title compound, K+·C5H11O8S−·H2O [systematic name: potassium (1S,2S,3S,4R-1,2,3,4,5-pentahydroxypentane-1-sulfonate monohydrate], formed by reaction of d-lyxose with potassium hydrogen sulfite in water, crystallizes as colourless square prisms. The anion has an open-chain structure in which the S atom, the C atoms of the sugar chain and the oxygen atom of the hydroxymethyl group form an essentially all-trans chain with the corresponding torsion angles lying between 178.61 (12 and 157.75 (10°. A three-dimensional bonding network exists in the crystal structure involving coordination of two crystallographically independent potassium ions by O atoms (one cation being hexa- and the other octa-coordinate, with each lying on a twofold rotation axis, and extensive intermolecular O—H...O hydrogen bonding.

  10. A second monoclinic polymorph of ethylenediammonium bis(hydrogen squarate monohydrate

    Directory of Open Access Journals (Sweden)

    Louiza Zenkhri

    2011-05-01

    Full Text Available The title compound, C2H10N22+·2HC4O4−·H2O, a new polymorph of ethylenediammonium bis(hydrogen squarate monohydrate, was synthesized by slow evaporation of an acid solution. The asymetric unit contains two hydrogen squarate anions, two half-molecules of protonated ethylenediamine arranged around a twofold axis and one water molecule. In the crystal, N—H...O and O—H...O hydrogen bonds between the hydrogen squarate anions, protonated N atoms from the amine group and water molecules lead to a three-dimensional framework. In particular, the cohesion between the squarate groups is ensured by very short intermolecular hydrogen bonds bonds. The title compound crystallized together with the previously reported polymorph [Mathew et al. (2002. J. Mol. Struct. 641, 263–279].

  11. Nucleation of Alpha lactose monohydrate induced using flow through a venturi orifice

    Science.gov (United States)

    McLeod, J. S.; Paterson, A. H. J.; Bronlund, J. E.; Jones, J. R.

    2010-03-01

    Nucleation is a determinant of the final crystal size distribution produced during a crystallization process. Other studies in the literature have shown that mixing influences alpha lactose monohydrate nucleation. To investigate this in more detail, three different sized Venturi orifices were used to provide a point of passive mixing for supersaturated lactose solutions. This system allowed the study of different factors associated with characterising the mixing process, including cavitation, power input, Reynolds number and vortex formation. A strong relationship was found between the number of vortices created in the system and the nucleation rate. It is speculated that the vortices decrease the distance required for diffusion of molecules in the system, increasing the rate at which they can come together to form a stable nuclei.

  12. N′-[(E-2-Hydroxy-5-iodobenzylidene]furan-2-carbohydrazide monohydrate

    Directory of Open Access Journals (Sweden)

    Rahman Bikas

    2012-02-01

    Full Text Available The organic molecule of the title monohydrate, C12H9IN2O3·H2O, features a disordered furyl ring with the major component [site occupancy = 0.575 (18] having the carbonyl O and furyl O atoms syn, and the other conformation having these atoms anti. The molecule is slightly twisted with the dihedral angle between the benzene and furyl rings being 10.3 (6° (major component. An intramolecular O—H...N(imine hydrogen bond is formed. In the crystal, the water molecule accepts a hydrogen bond from an amine H atom, and forms two O—H...O(carbonyl hydrogen bonds, thereby linking three different carbohydrazide molecules. The result is a supramolecular layer parallel to (001. The closest contacts between layers are of the type I...I, at a distance of 3.6986 (6 Å.

  13. Crystallization and Structure Determination of Fac-Triammin-Aquo-Oxalato-Cobalt (III-Nitrate Monohydrate

    Directory of Open Access Journals (Sweden)

    Cristian G. Hrib

    2014-11-01

    Full Text Available The title compound, fac-triammin-aquo-oxalato-cobalt(III-nitrate monohydrate, fac-[Co(NH33(C2O4(H2O]NO3·H2O (2, was prepared according to an original synthetic protocol published exactly 100 years ago by Alfred Werner by dissolving the indigo-blue non-electrolyte complex mer-triammin-chloro-oxalato-cobalt(III, mer-[Co(NH33(C2O4Cl] (1, in boiling half-concentrated nitric acid. Contrary to the literature, it did not crystallize directly from the reaction mixture, but crystallization could be induced by saturating the solution with NaClO4. The structure of 2 has monoclinic (P21/n symmetry. The crystal structure displays an extensive array of N–H···O and O–H···O hydrogen bonding.

  14. Papillary and Nonpapillary Calcium Oxalate Monohydrate Renal Calculi: Comparative Study of Etiologic Factors

    Directory of Open Access Journals (Sweden)

    Enrique Pieras

    2006-01-01

    Full Text Available Calcium oxalate monohydrate (COM renal calculi can be classified into two groups: papillary and nonpapillary. In this paper, a comparative study between etiologic factors of COM papillary and nonpapillary calculi is performed. The study included 40 patients with COM renal calculi. The urine of these individuals was analyzed. Case history, lifestyle, and dietetic habits were obtained.No significant differences between urinary biochemical data of both groups were observed; 50% of COM papillary stone formers and 40% of COM nonpapillary stone formers had urolithiasis family history. A low consumption of phytate-rich products was observed for both groups. A relationship between profession with occupational exposure to cytotoxic products and COM papillary renal lithiasis was detected.The results suggest that COM papillary calculi would be associated to papillary epithelium alterations together with a crystallization inhibitors deficit, whereas COM nonpapillary calculi would be associated to the presence of heterogeneous nucleants and a crystallization inhibitors deficit.

  15. Characterization studies on the additives mixed L-arginine phosphate monohydrate (LAP) crystals

    Energy Technology Data Exchange (ETDEWEB)

    Haja Hameed, A.S., E-mail: hajahameed2001@gmail.co [PG and Research Department of Physics, Jamal Mohamed College, Tiruchirappalli 620 020, Tamil Nadu (India); Karthikeyan, C. [PG and Research Department of Physics, Jamal Mohamed College, Tiruchirappalli 620 020, Tamil Nadu (India); Ravi, G. [Department of Physics, Alagappa University, Karaikudi 630 003 (India); Rohani, S. [Department of Chemical and Biochemical Engineering, The University of Western Ontario, London, Ontario, N6A 5B9 (Canada)

    2011-04-01

    L-arginine phosphate monohydrate (LAP), potassium thiocyanate (KSCN) mixed LAP (LAP:KSCN) and sodium sulfite (Na{sub 2}SO{sub 3}) mixed LAP (LAP:Na{sub 2}SO{sub 3}) single crystals were grown by slow cooling technique. The effect of microbial contamination and coloration on the growth solutions was studied. The crystalline powders of the grown crystals were examined by X-ray diffraction and the lattice parameters of the crystals were estimated. From the FTIR spectroscopic analysis, various functional group frequencies associated with the crystals were assigned. Vickers microhardness studies were done on {l_brace}1 0 0{r_brace} faces for pure and additives mixed LAP crystals. From the preliminary surface second harmonic generation (SHG) results, it was found that the SHG intensity at (1 0 0) face of LAP:KSCN crystal was much stronger than that of pure LAP.

  16. (E-4-Methoxy-N′-(2,4,5-trifluorobenzylidenebenzohydrazide monohydrate

    Directory of Open Access Journals (Sweden)

    R. Maheswari

    2016-05-01

    Full Text Available The title Schiff base compound, C15H11F3N2O2·H2O, crystallized as a monohydrate. The conformation about the C=N bond is E. The molecule is almost planar, with the dihedral angle between the planes of the methoxybenzene and trifluorobenzylidene rings being 7.46 (6°. In the crystal, molecules are linked by bifurcated Owater—H...(O,N hydrogen bonds and N—H...Owater and Owater—H...O and C—H...O hydrogen bonds, forming chains along [100]. The chains are linked by C—H...Owater hydrogen bonds, forming slabs parallel to the bc plane. Within the slabs there are offset π–π interactions present [intercentroid distance = 3.7883 (7 Å].

  17. Influence of process variable and physicochemical properties on the granulation mechanism of mannitol in a fluid bed top spray granulator.

    Science.gov (United States)

    Bouffard, Jonathan; Kaster, Meagan; Dumont, Hubert

    2005-10-01

    This study investigated the influence of specific process variables, including the hydroxypropyl cellulose (HPC) binder solution atomization, on the fluidized bed top spray granulation of mannitol. Special attention was given to the relationship between wetting and the granule growth profile. The atomization of the HPC binder solution using a binary nozzle arrangement produced droplets of decreasing size as the atomization pressure was increased, while changes in the spray rate had little effect on the mean droplet size. Increasing the HPC binder concentration from 2 to 8% w/w increased the binder droplet size and was most likely attributed to higher solution viscosity. The top spray granulation of mannitol showed induction type growth behavior. Process conditions like high spray rate, low fluidizing air velocity and binder solution concentration that promote the availability of HPC binder solution at the surface of the particles appeared to be key in enhancing nucleation and growth of the granules. Increasing the bed moisture level, up to a certain value, reduced the contribution of attrition to the overall growth profile of the granule and, more significantly, produced less granule breakage on drying. It was observed that the mean granule size could be reduced as much as 40% between the end of granulation and the end of drying for lower initial bed moisture level despite a shorter drying phase. High atomization pressure, especially when maintained during the drying phase, contributed substantially to granule breakage.

  18. Conditional knockout of tumor overexpressed gene in mouse neurons affects RNA granule assembly, granule translation, LTP and short term habituation.

    Directory of Open Access Journals (Sweden)

    Elisa Barbarese

    Full Text Available In neurons, specific RNAs are assembled into granules, which are translated in dendrites, however the functional consequences of granule assembly are not known. Tumor overexpressed gene (TOG is a granule-associated protein containing multiple binding sites for heterogeneous nuclear ribonucleoprotein (hnRNP A2, another granule component that recognizes cis-acting sequences called hnRNP A2 response elements (A2REs present in several granule RNAs. Translation in granules is sporadic, which is believed to reflect monosomal translation, with occasional bursts, which are believed to reflect polysomal translation. In this study, TOG expression was conditionally knocked out (TOG cKO in mouse hippocampal neurons using cre/lox technology. In TOG cKO cultured neurons granule assembly and bursty translation of activity-regulated cytoskeletal associated (ARC mRNA, an A2RE RNA, are disrupted. In TOG cKO brain slices synaptic sensitivity and long term potentiation (LTP are reduced. TOG cKO mice exhibit hyperactivity, perseveration and impaired short term habituation. These results suggest that in hippocampal neurons TOG is required for granule assembly, granule translation and synaptic plasticity, and affects behavior.

  19. Formulations in first encounters

    NARCIS (Netherlands)

    A. Hak (Tony); F. de Boer (Fijgje)

    1994-01-01

    markdownabstractThe paper describes and compares the use and function of the formulation--decision pair in three types of diagnostic interviewing. The investigatory type of interviewing, which typically occurs in the medical interview, is characterized by the absence of formulations. In the explora

  20. Rotational spectroscopy of the atmospheric photo-oxidation product o-toluic acid and its monohydrate.

    Science.gov (United States)

    Schnitzler, Elijah G; Zenchyzen, Brandi L M; Jäger, Wolfgang

    2016-01-07

    o-Toluic acid, a photo-oxidation product in the atmosphere, and its monohydrate were characterized in the gas phase by pure rotational spectroscopy. High-resolution spectra were measured in the range of 5-14 Hz using a cavity-based molecular beam Fourier-transform microwave spectrometer. Possible conformers were identified computationally, at the MP2/6-311++G(2df,2pd) level of theory. For both species, one conformer was identified experimentally, and no methyl internal rotation splittings were observed, indicative of relatively high barriers to rotation. In the monomer, rocking of the carboxylic acid group is a large amplitude motion, characterized by a symmetrical double-well potential. This and other low-lying out-of-plane vibrations contribute to a significant (methyl top-corrected) inertial defect (-1.09 amu Å(2)). In the monohydrate, wagging of the free hydrogen atom of water is a second large amplitude motion, so the average structure is planar. As a result, no c-type transitions were observed. Water tunneling splittings were not observed, because the water rotation coordinate is characterized by an asymmetrical double-well potential. Since the minima are not degenerate, tunneling is precluded. Furthermore, a concerted tunneling path involving simultaneous rotation of the water moiety and rocking of the carboxylic acid group is precluded, because the hilltop along this coordinate is a virtual, rather than a real, saddle-point. Inter- and intramolecular non-covalent bonding is discussed in terms of the quantum theory of atoms in molecules. The percentage of o-toluic acid hydrated in the atmosphere is estimated to be about 0.1% using statistical thermodynamics.

  1. Sustained-release microsphere formulation containing an agrochemical by polyurethane polymerization during an agitation granulation process.

    Science.gov (United States)

    Terada, Takatoshi; Tagami, Manabu; Ohtsubo, Toshiro; Iwao, Yasunori; Noguchi, Shuji; Itai, Shigeru

    2016-07-25

    In this report, a new solventless microencapsulation method by synthesizing polyurethane (PU) from polyol and isocyanate during an agglomeration process in a high-speed mixing apparatus was developed. Clothianidin (CTD), which is a neonicotinoid insecticide and highly effective against a wide variety of insect pests, was used as the model compound. The microencapsulated samples covered with PU (CTD microspheres) had a median diameter of dispersed in PU. Although voids appeared in the CTD microspheres after CTD release, the spherical shape of the microspheres remained stable and no change in its framework was observed. The experimental release data were highly consistent with the Baker-Lonsdale model derived from drug release of spherical monolithic dispersions and consistent with the computed tomography measurements.

  2. Preparation of high performance ceramic tiles using waste tile granules and ceramic polishing powder

    Institute of Scientific and Technical Information of China (English)

    WANG Gong-xun; SU Da-gen

    2008-01-01

    This paper presents an innovative approach to reusing waste tile granules (TG) and ceramic polishing powder (PP) to produce high performance ceramic tiles. We studied formulations each with a TG mass fraction of 25.0% and a different PP mass fraction between 1.0% and 7.0%. The formulations included a small amount of borax additive of a mass fracton between 0.2%and 1.2%. The effects of these industrial by-products on compressive strength, water absorption and microstructure of the new ceramic tiles were investigated. The results indicate that the compressive strength decreases and water absorption increases when TG with a mass fraction of 25.0% are added. Improvement of the compressive strength may be achieved when TG (up to 25.0%)and PP (up to 2.0%) are both used at the same time. In particular, the compressive strength improvement can be maximized and water absorption reduced when a borax additive of up to 0.5% is used as a flux. Scanning electron microscopy reveals that a certain amount of fine PP granules and a high content of fluxing oxides from borax avail the formation of glassy phase that fills up the pores in the new ceramic tiles, resulting in a dense product with high compressive strength and low water absorption.

  3. Rheological and fractal hydrodynamics of aerobic granules.

    Science.gov (United States)

    Tijani, H I; Abdullah, N; Yuzir, A; Ujang, Zaini

    2015-06-01

    The structural and hydrodynamic features for granules were characterized using settling experiments, predefined mathematical simulations and ImageJ-particle analyses. This study describes the rheological characterization of these biologically immobilized aggregates under non-Newtonian flows. The second order dimensional analysis defined as D2=1.795 for native clusters and D2=1.099 for dewatered clusters and a characteristic three-dimensional fractal dimension of 2.46 depicts that these relatively porous and differentially permeable fractals had a structural configuration in close proximity with that described for a compact sphere formed via cluster-cluster aggregation. The three-dimensional fractal dimension calculated via settling-fractal correlation, U∝l(D) to characterize immobilized granules validates the quantitative measurements used for describing its structural integrity and aggregate complexity. These results suggest that scaling relationships based on fractal geometry are vital for quantifying the effects of different laminar conditions on the aggregates' morphology and characteristics such as density, porosity, and projected surface area.

  4. Microbial granulation for lactic acid production

    DEFF Research Database (Denmark)

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon

    2016-01-01

    was fed with 2% glucose and operated at a hydraulic retention time (HRT) of 12 h and pH 5.0 ± 0.1 under a thermophilic condition (50°C). The mixed liquor in the CSTR was then transferred to an up-flow anaerobic sludge blanket reactor (UASB). The fermentation performance and granulation process were......This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which...... monitored with a gradual decrease of HRT from 8.0 to 0.17 h, corresponding to an increase in the substrate loading from 60 to 2,880 g glucose L−1d−1. As the operation continued, the accumulation of biomass in the UASB was clearly observed, which changed from flocculent to granular form with decrease in HRT...

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

    Science.gov (United States)

    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.

  6. Influence of pore water velocity on the release of carbofuran and fenamiphos from commercial granulates embedded in a porous matrix

    Science.gov (United States)

    Paradelo, Marcos; Pérez-Rodríguez, Paula; Arias-Estévez, Manuel; López-Periago, J. Eugenio

    2012-11-01

    Pore water flow velocity can influence the processes involved in the contaminant transport between relative stagnant zones of porous media and their adjacent mobile zones. A particular case of special interest is the occurrence of high flow rates around the controlled release granules containing pesticides buried in soil. The release of the pesticides carbofuran and fenamiphos from commercial controlled release formulations (CRFs) was studied, comparing release tests in a finite volume of water with water flow release tests in saturated packed sand at different seepage velocities. For water release kinetics, the time taken for 50% of the pesticide to be released (T50) was 0.64 hours for carbofuran and 1.97 hours for fenamiphos. In general, the release rate was lower in the porous matrix than in the free water tests. The faster release rate for carbofuran was attributed to its higher water diffusivity. The seepage velocity has a strong influence on the pesticide release rate. The dominant release mechanism varies with the progress of release. The evolution of the mechanism is discussed on the basis of the successive steps that involve the moving boundary of the dissolution front of the pesticide inside the granule, the concentration gradient inside the granule and the flow boundary layer resistance to solute diffusion around the granule. The pore water velocity influences the overall release dynamics. Therefore, seepage velocity should be considered in pesticide release to evaluate the risk of pesticide leaching, especially in scenarios with fast infiltration.

  7. How Deformation Behavior Controls Product Performance After Twin Screw Granulation With High Drug Loads and Crospovidone as Disintegrant.

    Science.gov (United States)

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

    2017-01-01

    This study addresses the quantitative influence of 12 different materials (active pharmaceutical ingredients and excipients as surrogate active pharmaceutical ingredients) on the critical quality attributes of twin screw granulated products and subsequently produced tablets. Prestudies demonstrated the significant influence of the chosen model materials (in combination with crospovidone) on the disintegration behavior of the resulting tablets, despite comparable tablet porosities. This study elucidates possible reasons for the varying disintegration behavior by investigating raw material, granule, and tablet properties. An answer could be found in the mechanical properties of the raw materials and the produced granules. Through compressibility studies, the materials could be classified into materials with high compressibility, which deform rather plastically under compression stress, and low compressibility, which display breakages under compression stress. In general, and apart from (pseudo)-polymorphic transformations, brittle materials featured excellent disintegration performance, even at low resulting tablet porosities <8%, whereas plastically deformable materials mostly did not reveal any disintegration. These findings must be considered in the development of simplified formulations with high drug loads, in which the active pharmaceutical ingredient predominantly defines the deformation behavior of the granule.

  8. Improved aerosolization performance of salbutamol sulfate formulated with lactose crystallized from binary mixtures of ethanol-acetone.

    Science.gov (United States)

    Kaialy, Waseem; Ticehurst, Martyn D; Murphy, John; Nokhodchi, Ali

    2011-07-01

    It has been shown that dry powder inhaler (DPI) formulations typically achieve low fine particle fractions (poor performance). A commonly held theory is that this is due, at least in part, to low levels of detachment of drug from lactose during aerosolization as a result of strong adhesion of drug particles to the carrier surfaces. Therefore, the purpose of the present study is to overcome poor aerosolization performance of DPI formulation by modification of lactose particles. Lactose particles were crystallized by adding solution in water to different ratios of binary mixtures of ethanol-acetone. The results showed that modified lactose particles had exceptional aerosolization performance that makes them superior to commercial lactose particles. Morphology assessment showed that crystallized lactose particles were less elongated, more irregular in shape, and composed of smaller primary lactose particles compared with commercial lactose. Solid-state characterization showed that commercial lactose particles were α-lactose monohydrate, whereas crystallized lactose particles were a mixture of α-lactose monohydrate and β-lactose according to the ratio of ethanol-acetone used during crystallization process. The enhanced performance could be mainly due to rougher surface and/or higher amounts of fines compared with the lactose crystallized from pure ethanol or commercial lactose. Copyright © 2011 Wiley-Liss, Inc. and the American Pharmacists Association

  9. 21 CFR 520.970a - Flunixin meglumine granules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Flunixin meglumine granules. 520.970a Section 520...) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.970a Flunixin meglumine granules. (a) Specifications. Each 10-gram packet contains flunixin meglumine equivalent to 250...

  10. Application of granulating of tires; Aplicaciones de granulado de NFUs

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Justicia, A.

    2001-07-01

    At present, used tires are mainly used as fuel, retreading and granulating of tires. In this article. I will focus on the last option, talking about some of the multiple applications and going into detail of the making process of the granulation of used tires in a recycling plant. (Author)

  11. Cerebellar Granule Cells: Dense, Rich and Evolving Representations

    NARCIS (Netherlands)

    Badura, Aleksandra; De Zeeuw, Chris I

    2017-01-01

    For half a century it was assumed that granule cells use ultra-sparse encoding, but now in vivo calcium-imaging studies have shown that large ensembles of granule cells provide dense signals, which themselves evolve and adapt during training.

  12. Osseous drill holes to promote granulation tissue: Radiologic appearance

    Energy Technology Data Exchange (ETDEWEB)

    Resnik, C.S.; Reiner, B.I.; Diaconis, J.N. (Maryland Univ. Medical System/Hospital, Baltimore, MD (USA). Dept. of Radiology); Goldberg, N.H. (Maryland Univ. Medical System/Hospital, Baltimore, MD (USA). Div. of Plastic Surgery)

    1991-04-01

    Skin grafting following extensive soft-tissue loss is often delayed until adequate granulation tissue can be generated. Surgical drill holes into the marrow cavity promote development of granulation tissue. This article illustrates the radiology appearance of these drill holes in four patients. (orig.).

  13. Investigation of Compost Fertilizer Granulation Parameters Using Response Surface Methodology

    Directory of Open Access Journals (Sweden)

    Y Ghasemi

    2015-03-01

    Full Text Available Nowadays compost fertilizers are suitable alternative to chemical fertilizers, due to the threats for human health and agriculture products. The most important problems for applying the compost fertilizer in the farm are: transportation (high volume, high moisture content, spreading problem, impurity such as dust and storage. To solve the problems mentioned, pressing process such as converting the compost to pellets and granules are suggested. In this research the effects of some granulation parameters on the percent of useful granules in a laboratory scale rotating drum was evaluated. The percentage of useful granules decreased by increasing the granulation time and increased by increasing the percentage of drum filling. The optimal conditions for granules production was achieved at drum rotational speed of 40.38 rpm, granulation time of 15 min, drum filling of 10% and molasse percentage of 40.97. According to these conditions, the response for useful granule was estimated as 81.6% with R2 of 0.924.

  14. Proteoglycans support proper granule formation in pancreatic acinar cells.

    Science.gov (United States)

    Aroso, Miguel; Agricola, Brigitte; Hacker, Christian; Schrader, Michael

    2015-10-01

    Zymogen granules (ZG) are specialized organelles in the exocrine pancreas which allow digestive enzyme storage and regulated secretion. The molecular mechanisms of their biogenesis and the sorting of zymogens are still incompletely understood. Here, we investigated the role of proteoglycans in granule formation and secretion of zymogens in pancreatic AR42J cells, an acinar model system. Cupromeronic Blue cytochemistry and biochemical studies revealed an association of proteoglycans primarily with the granule membrane. Removal of proteoglycans by carbonate treatment led to a loss of membrane curvature indicating a supportive role in the maintenance of membrane shape and stability. Chemical inhibition of proteoglycan synthesis impaired the formation of normal electron-dense granules in AR42J cells and resulted in the formation of unusually small granule structures. These structures still contained the zymogen carboxypeptidase, a cargo molecule of secretory granules, but migrated to lighter fractions after density gradient centrifugation. Furthermore, the basal secretion of amylase was increased in AR42J cells after inhibitor treatment. In addition, irregular-shaped granules appeared in pancreatic lobules. We conclude that the assembly of a proteoglycan scaffold at the ZG membrane is supporting efficient packaging of zymogens and the proper formation of stimulus-competent storage granules in acinar cells of the pancreas.

  15. Monetite granules versus particulate autologous bone in bone regeneration.

    Science.gov (United States)

    Torres, Jesús; Tamimi, Iskandar; Cabrejos-Azama, Jatsue; Tresguerres, Isabel; Alkhraisat, Mohammad; López-Cabarcos, Enrique; Hernández, Gonzalo; Tamimi, Faleh

    2015-07-01

    The aim of this study was to test bone tissue response to monetite granules in comparison with intramembranous autologous bone graft in a rabbit calvaria critical size defect model. Novel monetite granules were synthesized by thermal conversion of set brushite cement. Eight female New Zealand rabbits were used for this study. Two identical 10mm diameter bicortical cranial defects were created in each animal. One of the defects was grafted with monetite granules while the contralateral was grafted with granules of intramembranous autologous bone as control. Animals were sacrificed 8 weeks after surgery and biopsies were taken for histological and histomorphometrical evaluation under light microscopy. Wilcoxon test was used for statistical analysis. The bone defects treated with either autologous bone or monetite granules were able to heal within the study period. Upon histological observation the defects treated with autologous bone granules resembled the adjacent intact calvaria, whereas the defects treated with monetite showed a high infiltration of new bone and only 13.4±8.4% of remaining granules. The percentage of bone volume in the defects of the control group (71±9%) was 16% higher than in the study group (55±10%) (p0.05). The amount of augmented mineralized tissue in the bone defects obtained with monetite granules was not significantly different from that obtained with autologous bone. This study confirms the potential of monetite based biomaterials as an alternative to autologous bone graft. Copyright © 2015 Elsevier GmbH. All rights reserved.

  16. The Color of Lactotroph Secretory Granules Stained with FM1-43 Depends on Dye Concentration

    OpenAIRE

    Johnson, Joseph M.; Betz, William J.

    2007-01-01

    When pituitary lactotroph granules undergo exocytosis in the presence of FM1-43, their cores absorb dye and fluoresce brightly. We report that different granules fluoresce with different colors, despite being stained with a single fluorescent dye; emission spectra from individual granules show up to a 25 nm difference between the greenest and reddest granules. We found a correlation between granule color and average fluorescence intensity, suggesting that granule color depends upon dye concen...

  17. Understanding and predicting bed humidity in fluidized bed granulation.

    Science.gov (United States)

    Hu, Xinhui; Cunningham, John; Winstead, Denita

    2008-04-01

    Bed humidity is a critical parameter that needs to be controlled in a fluidized bed granulation to ensure reliability. To predict and control the bed humidity during the fluidized bed granulation process, a simple model based on the mass conservation of moisture was developed. The moisture mass balance model quantitatively simulates the effects of spray rate, binder solution concentration, airflow rate, inlet air temperature, and dew point on the bed humidity. The model was validated by a series of granulations performed in different scale granulators including Glatt GPCG-1, GPCG-15, and GPCG-60. Good agreement was observed between the theoretical prediction and the measured loss on drying (LOD). The model developed in the current work enables us to choose the appropriate parameters for the fluidized bed granulation and can be used as a valuable tool in process scaling-up.

  18. A Calculus on Granules from Rough Inclusions in Information Systems

    Institute of Scientific and Technical Information of China (English)

    Lech Polkowski

    2006-01-01

    Indiscernibility relations induced in information systems in the sense of Pawlak,define granules of knowledge as unions of their equivalence classes,leading to regular structures like Boolean algebras. Apart from Boolean operations on granules, under afixed set of attributes,that induce the partition topology on their collection, one may search for more flexible schemes that would induce in collections of granules some non-trivial topologies and in particular quasi-metrics on granules, allowing for richer structures. A way of realization of this program has been proposed as the paradigm of rough mereology; although abstract, stemming from an alternative set theory, yet it offers a calculus based on kind of quasi-metrics that allows for discussing granules from the point of view of their closeness. In thiswork, we would liketopresent theideas of this approach and basic results with short discussion of applications.

  19. Formulation techniques for nanofluids.

    Science.gov (United States)

    Rivera-Solorio, Carlos I; Payán-Rodríguez, Luis A; García-Cuéllar, Alejandro J; Ramón-Raygoza, E D; L Cadena-de-la-Peña, Natalia; Medina-Carreón, David

    2013-11-01

    Fluids with suspended nanoparticles, commonly known as nanofluids, may be formulated to improve the thermal performance of industrial heat transfer systems and applications. Nanofluids may show enhanced thermal and electrical properties such as thermal conductivity, viscosity, heat transfer coefficient, dielectric strength, etc. However, stability problems may arise as nanoparticles usually have the tendency to agglomerate and sediment producing deterioration in the increment of these properties. In this review, we discuss patents that report advances in the formulation of nanofluids including: production methods, selection of components (nanoparticles, base fluid and surfactants), their chemical compositions and morphologies, and characterization techniques. Finally, current and future directions in the development of nanofluid formulation are discussed.

  20. FORMULATION DEVELOPMENT AND EVALUATION OF NAPROXEN SODIUM TABLETS USP

    Directory of Open Access Journals (Sweden)

    *RANGASAMY MANIVANNAN, KUGALUR GANESAN PARTHIBAN, SANAULLAH SHAIK, BALASUBRAMANIAM SENTHILKUMAR AND NATESAN SENTHILKUMAR

    2010-03-01

    Full Text Available The objective of the present study is to develop a pharmaceutically stable and robust formulation ofNaproxen sodium tablets USP 220mg comparable with innovator. In the present study we are reducing theexcipients there by we can reduce the cost of the dosage form. The tablets of Naproxen sodium USP 220mg weresuccessfully prepared by using wet granulation technique. Several trial formulations i.e., from F1-F10 havebeen taken to optimize and develop a robust formulation. The prepared tablets were evaluated for weightvariation, hardness, thickness, friability, % drug content, disintegration time and in vitro drug release.Formulation F10 showed a drug release of 103.5% in 60mins which is faster than the innovator product. Thestability studies, shown that the formulation F10, F11 and F12 were stable enough at 400C / 75% RH for aperiod of 3 months. Therefore it can be concluded that the formulation F10 (Naproxen sodium tablets USP220mg is robust and stable.

  1. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Directory of Open Access Journals (Sweden)

    Seiichiro eJinde

    2013-02-01

    Full Text Available Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability – the dormant basket cell and the irritable mossy cell hypotheses. The dormant basket cell hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The irritable mossy cell hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

  2. Electron attachment to the guanine-cytosine nucleic acid base pair and the effects of monohydration and proton transfer.

    Science.gov (United States)

    Gupta, Ashutosh; Jaeger, Heather M; Compaan, Katherine R; Schaefer, Henry F

    2012-05-17

    The guanine-cytosine (GC) radical anion and its interaction with a single water molecule is studied using ab initio and density functional methods. Z-averaged second-order perturbation theory (ZAPT2) was applied to GC radical anion for the first time. Predicted spin densities show that the radical character is localized on cytosine. The Watson-Crick monohydrated GC anion is compared to neutral GC·H2O, as well as to the proton-transferred analogue on the basis of structural and energetic properties. In all three systems, local minima are identified that correspond to water positioned in the major and minor grooves of macromolecular DNA. On the anionic surface, two novel structures have water positioned above or below the GC plane. On the neutral and anionic surfaces, the global minimum can be described as water interacting with the minor groove. These structures are predicted to have hydration energies of 9.7 and 11.8 kcal mol(-1), respectively. Upon interbase proton-transfer (PT), the anionic global minimum has water positioned in the major groove, and the hydration energy increases to 13.4 kcal mol(-1). PT GC·H2O(•-) has distonic character; the radical character resides on cytosine, while the negative charge is localized on guanine. The effects of proton transfer are further investigated through the computed adiabatic electron affinities (AEA) of GC and monohydrated GC, and the vertical detachment energies (VDE) of the corresponding anions. Monohydration increases the AEAs and VDEs by only 0.1 eV, while proton-transfer increases the VDEs substantially (0.8 eV). The molecular charge distribution of monohydrated guanine-cytosine radical anion depends heavily on interbase proton transfer.

  3. A highly sustainable and versatile granulation method of nanodrugs via their electrostatic adsorption onto chitosan microparticles as the granulation substrates.

    Science.gov (United States)

    Yang, Yue; Hadinoto, Kunn

    2013-08-16

    Nanodrugs play important roles in enhancing the sustainability of pharmaceutical manufacturing via their ability to enhance the bioavailability of poorly soluble drugs, resulting in less drug wastage and less mass/energy consumed in their manufacturing. Despite their sustainability enhancement capability, solid dosage form manufacturing of nanodrugs remains lacking from the sustainability perspective. One example is the granulation of nanodrugs prior to tablet preparation, where existing methods (e.g. wet granulation, spray granulation, spray drying) require high energy and time expenses, or are highly intricate often leading to product inconsistencies. Herein we present an alternative nanodrug granulation method via electrostatic adsorption of the nanodrugs onto chitosan microparticles acting as granulation substrates. The method is sustainable involving only mixing of aqueous suspensions of the nanodrugs and substrates under ambient conditions, followed by washing and drying. We investigate the effects of substrate's physical characteristics and nanodrug to substrate ratio on the nanodrug loading in the granules, content uniformity, nanodrug recovery, and granule flowability. Ciprofloxacin and curcumin nanoplexes prepared by drug-polyelectrolyte complexation are used as the model nanodrugs with neutrally, positively, and negatively charged chitosan microparticles as the substrates. Granules having 25% (w/w) nanodrug loading at 50% (w/w) recovery with good flowability have been successfully prepared. Copyright © 2013 Elsevier B.V. All rights reserved.

  4. Development of flexible and dispersible oral formulations containing praziquantel for potential schistosomiasis treatment of pre-school age children.

    Science.gov (United States)

    Trastullo, Ramona; Dolci, Luisa Stella; Passerini, Nadia; Albertini, Beatrice

    2015-11-10

    Praziquantel (PZQ), an anthelmintic drug used in developing countries for the treatment of schistosome infections, was processed using the fluid bed wet granulation technology to prepare fast dispersible granules, as an appropriate and flexible dosage form for pre-school-aged children. Granulation experiments were performed incorporating PZQ either in the powder mixture, according to the traditional way, or in the liquid phase containing wetting agents. In the powder mixture several excipients were tested: Flowlac 100 as filler, Galeniq 721 (isomalt) and Neosorb P 100 T (D-sorbitol) as sweeteners and PVP K30 as binder; while in the liquid phase Lutrol F68, Cremophor RH 40 or Tween 80 as surfactants were investigated. Different formulations loaded with 10% w/w (batches 1-8) and 20% w/w of PZQ (batches 9-13) were produced The majority of granules displayed good flow properties and uniform drug content. X-ray powder diffraction showed that PZQ remained in its original crystalline state, while differential scanning calorimetry and Fourier transform-infrared analysis evidenced the formation of chemical interactions among the ingredients. The solubilisation test performed in non-sink condition to reproduce the actual condition in which a child of 4 years takes the medicine revealed that granules quickly formed a very fine suspension in water (dV90=39.9 μm). Although after the granulation process the solubility of raw PZQ was not increased, adding the aqueous suspension to 500 ml of buffer solution of pH 1.5, simulating the fasted state of a child, 50% of the drug was dissolved after 30 min. After granule manipulation with milk and fruit juices, no PZQ degradation was observed during time. Finally, the selected granule formulation provided evidence to be stable even at hot and very humid climate (30°C/75% RH), at least for the examined time.

  5. Assessment of strategy formulation

    DEFF Research Database (Denmark)

    Acur, Nuran; Englyst, Linda

    2006-01-01

    . Practical implications – The integration of three different strategy assessment approaches has been made to obtain a holistic, multi-perspective reflection on strategy formulation. Such reflection is assumed to enable managers to proactively evaluate the potential outcome and performance of their chosen......Purpose – Today, industrial firms need to cope with competitive challenges related to innovation, dynamic responses, knowledge sharing, etc. by means of effective and dynamic strategy formulation. In light of these challenges, the purpose of the paper is to present and evaluate an assessment tool...... for strategy formulation processes that ensures high quality in process and outcome. Design/methodology/approach – A literature review was conducted to identify success criteria for strategy formulation processes. Then, a simple questionnaire and assessment tool was developed and used to test the validity...

  6. Fluidization of Wet Granulates under Hydrodynamic Shear

    CERN Document Server

    Battiato, I

    2012-01-01

    We investigate the fluidization threshold of three-dimensional cohesive granulates under hydrodynamic shear forces exerted by a creeping ow. A continuum model of flow through porous media provides an analytical expression for the average drag force on a single grain. The balance equation for the forces and a force propagation model are then used to investigate the effects of porosity and packing structure on the stability of the pile. We obtain a closed-form expression for the fluidization threshold of a regular packing of mono-disperse frictionless cohesive spherical grains in a planar fracture. The compound effect of structural (packing orientation and porosity) and dynamical properties of the system on its stability is quantified.

  7. TASTE MASKING METHODS AND AGENTS IN PHARMACEUTICAL FORMULATIONS

    Directory of Open Access Journals (Sweden)

    Mirajkar Reshma Nilesh

    2012-08-01

    Full Text Available Taste is a critical factor during development of any dosage form and it is important parameter in administering drugs orally. Undesirable and particularly bitter taste is one of the important formulation problems that are encountered with many drugs. Proven methods for bitterness reduction and inhibition have resulted in improved palatability of oral pharmaceuticals. The present review explains in detail the various methods and agents used for taste-masking like, Inclusion complexation, Ion exchange resin, Coating, Granulation, Microencapsulation, Flavors, and Sweeteners, Pro-drug etc.The review also highlights factors affecting the selection of technology for taste masking and methods for evaluation of taste.

  8. Cerebellar granule cells are predominantly generated by terminal symmetric divisions of granule cell precursors.

    Science.gov (United States)

    Nakashima, Kie; Umeshima, Hiroki; Kengaku, Mineko

    2015-06-01

    Neurons in the central nervous system (CNS) are generated by symmetric and asymmetric cell division of neural stem cells and their derivative progenitor cells. Cerebellar granule cells are the most abundant neurons in the CNS, and are generated by intensive cell division of granule cell precursors (GCPs) during postnatal development. Dysregulation of GCP cell cycle is causal for some subtypes of medulloblastoma. However, the details and mechanisms underlying neurogenesis from GCPs are not well understood. Using long-term live-cell imaging of proliferating GCPs transfected with a fluorescent newborn-granule cell marker, we found that GCPs underwent predominantly symmetric divisions, generating two GCPs or two neurons, while asymmetric divisions generating a GCP and a neuron were only occasionally observed, in both dissociated culture and within tissues of isolated cerebellar lobules. We found no significant difference in cell cycle length between proliferative and neurogenic divisions, or any consistent changes in cell cycle length during repeated proliferative division. Unlike neural stem cells in the cerebral cortex and spinal cord, which generate many neurons by repeated asymmetric division, cerebellar GCPs produce neurons predominantly by terminal symmetric division. These results indicate diverse mechanisms of neurogenesis in the mammalian brain. © 2015 Wiley Periodicals, Inc.

  9. A Granule Model for Evaluating Adhesion of Pharmaceutical Binders

    Directory of Open Access Journals (Sweden)

    Hossein Orafai

    2003-10-01

    Full Text Available Granule capability is defined in terms of the strength of individual granule and friability of granulation batch to withstand breaking, abrasion and compactibility. Binder(s are added to perform the above properties .The common methods to asses their capability are to test crushing strength of the granules directly and to make statistical analysis and /or testing the friability of bulk granulation. In this work four substrate models including polymethylmetacrylate beads(PMMA,glass powder, acetaminophen, and para-aminobebzoic acid were chosen. The binder models were corn starch, gelatin, methylcellulose (MC and hydroxypropylmethylcellulose (HPMC. After massing the substrates with the binder solutions, discs were produced by the mean of the mold technique. The discs were dried and conditioned and then tested for tensile strength while the failed areas were scanned by SEM. Various granulations were made and the results of friability and crush strength were compared with the discs strength .The bond areas in the SEM showed the trend with the binder concentration .A comparison of the standard deviation shows that discs have much lower level of the strength than granules. The resulting discs showed a higher performance which is related to the stems for the discs shape .In conclusion, this method is a simple and is applicable to differentiate efficacy of binder under studies.

  10. Optimization for blast furnace slag dry cooling granulation device

    Science.gov (United States)

    Dazhan, Sheng; Yali, Wang; Ruiyun, Wang; Suping, Cui; Xiaoyu, Ma

    2017-03-01

    Since the large accumulation amount of blast furnace slag (BFS) with recycling value, it has become a hot topic for recovery utilization. Compared with the existing various BFS granulation process, the dry granulation process can promote the use of blast furnace granulated slag as cement substitute and concrete admixtures. Our research group developed a novel dry cooling granulation experiment device to treat BFS. However, there are still some problems to be solved. The purpose of this research is to improve the cooling and granulation efficiency of the existing dry type cooling equipment. This topic uses the FLUENT simulation software to study the impact of the number of air inlet on the cooling effect of the device. The simulation result is that the device possessing eight air inlets can increase the number of hot and cold gas exchanged, resulting in a better cooling effect. According to the power consumption, LCA analysis was carried out on the cooling granulation process. The results show that the device equipped eight air inlets not only improved the original equipment cooling granulation effect, but also increased resource utilization ratio, realized energy-saving and emission reduction.

  11. UNCERTAINTY HANDLING IN DISASTER MANAGEMENT USING HIERARCHICAL ROUGH SET GRANULATION

    Directory of Open Access Journals (Sweden)

    H. Sheikhian

    2015-08-01

    Full Text Available Uncertainty is one of the main concerns in geospatial data analysis. It affects different parts of decision making based on such data. In this paper, a new methodology to handle uncertainty for multi-criteria decision making problems is proposed. It integrates hierarchical rough granulation and rule extraction to build an accurate classifier. Rough granulation provides information granules with a detailed quality assessment. The granules are the basis for the rule extraction in granular computing, which applies quality measures on the rules to obtain the best set of classification rules. The proposed methodology is applied to assess seismic physical vulnerability in Tehran. Six effective criteria reflecting building age, height and material, topographic slope and earthquake intensity of the North Tehran fault have been tested. The criteria were discretized and the data set was granulated using a hierarchical rough method, where the best describing granules are determined according to the quality measures. The granules are fed into the granular computing algorithm resulting in classification rules that provide the highest prediction quality. This detailed uncertainty management resulted in 84% accuracy in prediction in a training data set. It was applied next to the whole study area to obtain the seismic vulnerability map of Tehran. A sensitivity analysis proved that earthquake intensity is the most effective criterion in the seismic vulnerability assessment of Tehran.

  12. Encapsulated mesalamine granules (Apriso) for ulcerative colitis.

    Science.gov (United States)

    2009-05-18

    Apriso (Salix) is a new formulation of mesalamine (5-aminosalicylic acid; 5-ASA) approved by the FDA for maintenance of remission in mild to moderate ulcerative colitis (UC). Mesalamine is a locally acting antiinflammatory agent that is widely used both to maintain and induce remission in inflammatory bowel disease. Various mesalamine formulations have been developed to target drug delivery to areas of the small intestine and colon. Most of these agents require frequent dosing and have a high pill burden. The newest products--Lialda, introduced in 2007, and now Apriso--can be dosed once daily.

  13. Dispersal of Formulations of Fusarium oxysporum f. sp. erythroxyli and F. oxysporum f. sp. melonis by Ants.

    Science.gov (United States)

    Gracia-Garza, J A; Fravel, D R; Bailey, B A; Hebbar, P K

    1998-03-01

    ABSTRACT A natural epidemic of Fusarium wilt on coca (Erythroxylum coca) in Peru prompted the suggestion of possibly using the pathogen Fusarium oxysporum f. sp. erythroxyli as a mycoherbicide against this narcotic plant. During field trials conducted in Kauai, HI, to test the pathogenicity of the coca wilt pathogen, ants were observed removing formulations from test plots. While removal of formulations by ants was considered detrimental with respect to conducting field tests, ant removal was considered potentially beneficial in disseminating the mycoherbicide. Thus, research was initiated to assess the ability of formulation additives to alter the preference of ants for the formulated mycoherbicide. In Hawaii, preference of indigenous ants for removing formulations was tested using three different food bases (rice, rice plus canola oil, and wheat flour [gluten]). Similar tests were conducted at Beltsville, MD, using F. oxysporum f. sp. melonis, in which the formulation based on wheat flour was replaced by a formulation based on canola meal. Formulations based on wheat were preferred by ants in both locations; up to 90% of the wheat plus rice flour granules (C-6) and the wheat gluten plus kaolin granules (pesta) were removed within 24 h, while only 20% of those containing rice without oils were taken. However, when either canola, sunflower (Maryland only), or olive oil was added to the rice formulation, up to 90% of the granules were taken. The formulation based on canola meal was less attractive to ants, as only 65% of the granules were removed within a period of 24 h. Ants showed no preference with respect to presence or absence of fungal biomass. To alter the attractiveness of the C-6 formulation to ants, C-6 was amended with three natural products. Canna and tansy leaves were added to C-6 at a ratio of 1:5 (wt/wt), while chili powder was added at 1:25 or 1:2.5 (wt/wt). Canna, tansy, and the higher rate of chili powder significantly reduced the number of C-6

  14. Fumaric acid microenvironment tablet formulation and process development for crystalline cenicriviroc mesylate, a BCS IV compound.

    Science.gov (United States)

    Menning, Mark M; Dalziel, Sean M

    2013-11-04

    Cenicriviroc mesylate (CVC) is a potent dual antagonist of C-C chemokine receptor type 5 (CCR5) and C-C chemokine receptor type 2 (CCR2) in phase 2b development as an entry inhibitor for HIV-1 infection treatment.1,2 CVC is a weak base exhibiting BCS IV characteristics with a highly pH dependent solubility profile (>100 mg/mL for pH 4) and low Caco-2 cell line permeability. Previous tablet formulations of CVC, including spray-dried dispersion and a wet granulation with citric acid, had been found unacceptable for commercial use due to chemical and physical instability or unacceptably high excipient loading precluding fixed-dose combinability. A high drug loading, 26% (w/w), acidic microenvironment tablet formulation with fumaric acid solubilizer (1:1 CVC/fumaric acid) and a dry granulation process was developed iteratively through a sequence of prototypes characterized by beagle dog absorption studies, focused beam reflectance measurement (FBRM), dynamic vapor sorption (DVS), and accelerated stability testing. The fumaric acid based dry granulated product demonstrated a mean bioavailability comparable to an oral solution dose in a dog model. Stability and moisture sensitivity of the formulation were improved via the dry granulation process technique and the use of fumaric acid. It is hypothesized that the observed slow dissolution kinetics of fumaric acid prolongs an acidic microenvironment around the agglomerated CVC crystals and excipients leading to increased CVC dissolution and thereby absorption. The fumaric acid formulation also demonstrated absorption resilience to gastric pH extremes in a dog model. This optimized formulation and process enables CVC to be a viable candidate for current HIV treatment paradigms of single once daily fixed-dose combination products.

  15. Dosage Response Mortality of Japanese Beetle, Masked Chafer, and June Beetle (Coleoptera: Scarabaeidae) Adults When Exposed to Experimental and Commercially Available Granules Containing Metarhizium brunneum.

    Science.gov (United States)

    Behle, Robert W; Goett, Erica J

    2016-05-01

    Field-collected adults of three genera of turf-infesting scarabs, Japanese beetle (Popillia japonica Newman), June beetles (Phyllophaga spp.), and masked chafers (Cyclocephala spp.), were exposed to experimental and commercial granule formulations of the entomopathogenic fungus Metarhizium brunneum (Petch) strain F52 to determine their relative susceptibility. Experimental granules contained microsclerotia produced by liquid fermentation with the ability to produce fresh conidia when rehydrated and commercial granules were Met 52 granular bioinsecticide. All three groups of scarab adults showed a positive dosage response to the fungus when exposed in cups of potting mix treated with the granules. LC50 values for microsclerotia granules were 1.9 × 10(7), 7.1 × 10(6), and 3.2 × 10(6) conidia cup(-1) for P. japonica, Phyllophaga spp., and Cyclocephala spp., respectively. LC50 values for Met 52 granules were 5.9 × 10(7), 5.1 × 10(7), and 7.6 × 10(6) conidia cup(-1), respectively. The experimental granules containing microsclerotia show promise as a viable commercial control agent. They can be produced using lower cost fermentation methods and applied at lower dosages (97 g for 100 m(2) as opposed to 489 g per 100 m(2) for Met 52). If M. brunneum is applied to control the aforementioned white grubs, our data indicate the potential for the adult beetles to also be infected as they enter the soil to lay eggs. © The Authors 2016. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. The Leader Protein of Cardioviruses Inhibits Stress Granule Assembly ▿

    Science.gov (United States)

    Borghese, Fabian; Michiels, Thomas

    2011-01-01

    Stress granules (SG) are cytoplasmic aggregates of stalled translation preinitiation complexes that form in cells exposed to various environmental stresses. Here, we show that stress granules assemble in cells infected with Theiler's murine encephalomyelitis virus (TMEV) mutants carrying alterations in the leader (L) protein, but not in cells infected with wild-type TMEV. Stress granules also formed in STAT1-deficient cells, suggesting that SG formation was not a consequence of increased type I interferon (IFN) production when cells were infected with the mutant virus. Ectopic expression of the wild-type L protein was sufficient to inhibit stress granule formation induced by sodium arsenite or thapsigargin treatment. In conclusion, TMEV infection induces stress granule assembly, but this process is inhibited by the L protein. Unlike poliovirus-induced stress granules, TMEV-induced stress granules did not contain the nuclear protein Sam68 but contained polypyrimidine tract binding protein (PTB), an internal ribosome entry site (IRES)-interacting protein. Moreover, G3BP was not degraded and was found in SG after TMEV infection, suggesting that SG content could be virus specific. Despite the colocalization of PTB with SG and the known interaction of PTB with viral RNA, in situ hybridization and immunofluorescence assays failed to detect viral RNA trapped in infection-induced SG. Recombinant Theiler's viruses expressing the L protein of Saffold virus 2 (SAFV-2), a closely related human theilovirus, or the L protein of mengovirus, an encephalomyocarditis virus (EMCV) strain, also inhibited infection-induced stress granule assembly, suggesting that stress granule antagonism is a common feature of cardiovirus L proteins. PMID:21752908

  17. The leader protein of cardioviruses inhibits stress granule assembly.

    Science.gov (United States)

    Borghese, Fabian; Michiels, Thomas

    2011-09-01

    Stress granules (SG) are cytoplasmic aggregates of stalled translation preinitiation complexes that form in cells exposed to various environmental stresses. Here, we show that stress granules assemble in cells infected with Theiler's murine encephalomyelitis virus (TMEV) mutants carrying alterations in the leader (L) protein, but not in cells infected with wild-type TMEV. Stress granules also formed in STAT1-deficient cells, suggesting that SG formation was not a consequence of increased type I interferon (IFN) production when cells were infected with the mutant virus. Ectopic expression of the wild-type L protein was sufficient to inhibit stress granule formation induced by sodium arsenite or thapsigargin treatment. In conclusion, TMEV infection induces stress granule assembly, but this process is inhibited by the L protein. Unlike poliovirus-induced stress granules, TMEV-induced stress granules did not contain the nuclear protein Sam68 but contained polypyrimidine tract binding protein (PTB), an internal ribosome entry site (IRES)-interacting protein. Moreover, G3BP was not degraded and was found in SG after TMEV infection, suggesting that SG content could be virus specific. Despite the colocalization of PTB with SG and the known interaction of PTB with viral RNA, in situ hybridization and immunofluorescence assays failed to detect viral RNA trapped in infection-induced SG. Recombinant Theiler's viruses expressing the L protein of Saffold virus 2 (SAFV-2), a closely related human theilovirus, or the L protein of mengovirus, an encephalomyocarditis virus (EMCV) strain, also inhibited infection-induced stress granule assembly, suggesting that stress granule antagonism is a common feature of cardiovirus L proteins.

  18. Stearic acid and high molecular weight PEO as matrix for the highly water soluble metoprolol tartrate in continuous twin-screw melt granulation.

    Science.gov (United States)

    Monteyne, Tinne; Adriaensens, Peter; Brouckaert, Davinia; Remon, Jean-Paul; Vervaet, Chris; De Beer, Thomas

    2016-10-15

    Granules with release-sustaining properties were developed by twin screw hot melt granulation (HMG) using a combination of stearic acid (SA) and high molecular weight polyethylene oxide (PEO) as matrix for a highly water soluble model drug, metoprolol tartrate (MPT). Earlier studies demonstrated that mixing molten SA and PEO resulted in hydrogen bond formation between hydroxyl groups of fatty acid molecules and ether groups in PEO chains. These molecular interactions might be beneficial in order to elevate the sustained release effect of drugs from a SA/PEO matrix. This study aims to investigate the continuous twin screw melt granulation technique to study the impact of a SA/PEO matrix on the dissolution rate of a highly water soluble drug (MPT). Decreasing the SA/PEO ratio improved the release-sustaining properties of the matrix. The solid state of the granules was characterized using differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), X-ray diffraction (XRD), Raman spectroscopy, Fourier transform infrared (FTIR) and near infrared chemical imaging (NIR-CI) in order to understand the dissolution behavior. The results revealed a preferential interaction of the MPT molecules with stearic acid impeding the PEO to form hydrogen bonds with the stearic acid chains. However, this allowed the PEO chains to recrystallize inside the stearic acid matrix after granulation, hence, elevating the release-sustaining characteristics of the formulation.

  19. Zinc sulfide in intestinal cell granules of Ancylostoma caninum adults

    Energy Technology Data Exchange (ETDEWEB)

    Gianotti, A.J.; Clark, D.T.; Dash, J. (Portland State Univ., OR (USA))

    1991-04-01

    A source of confusion has existed since the turn of the century about the reddish brown, weakly birefringent 'sphaerocrystals' located in the intestines of strongyle nematodes, Strongylus and Ancylostoma. X-ray diffraction and energy dispersive spectrometric analyses were used for accurate determination of the crystalline order and elemental composition of the granules in the canine hookworm Ancylostoma caninum. The composition of the intestinal pigmented granules was identified unequivocally as zinc sulfide. It seems most probable that the granules serve to detoxify high levels of metallic ions (specifically zinc) present due to the large intake of host blood.

  20. Formulations and nebulizer performance.

    Science.gov (United States)

    O'Riordan, Thomas G

    2002-11-01

    To deliver a drug by nebulization, the drug must first be dispersed in a liquid (usually aqueous) medium. After application of a dispersing force (either a jet of gas or ultrasonic waves), the drug particles are contained within the aerosol droplets, which are then inhaled. Some drugs readily dissolve in water, whereas others need a cosolvent such as ethanol or propylene glycol. Some drugs are delivered as suspensions, and the efficiency of nebulizers can be different for solutions and suspensions. Solutions are delivered more efficiently with most devices. In general, conventional ultrasonic nebulizers should not be used to aerosolize suspensions, because of low efficiency. Newer strategies to improve the delivery of non-water-soluble drugs include the use of liposomes and the milling of the drug into very small "nanoparticles." In addition to the active therapeutic ingredient and solvents, drug formulations may include buffers (the solubility of some medications is influenced by pH), stabilizers, and, in the case of multi-dose preparations, antibacterial agents. Though formulations are designed to optimize drug solubility and stability, changes in formulation can also affect inhaled mass, particle size, and treatment time, though the differences between nebulizer brands probably have a greater impact than differences in formulation. Ultrasonic and jet nebulizers may damage protein and other complex agents through heat or shear stress. Additives to multi-dose formulations, especially antimicrobial and chelating agents, may cause adverse events, so there is a trend towards single-use, preservative-free vials.

  1. Modifying sorbents in controlled release formulations to prevent herbicides pollution

    Energy Technology Data Exchange (ETDEWEB)

    Cespedes, F.F.; Sanchez, M.V.; Garcia, S.P.; Perez, M.F. [University of Almeria, Almeria (Spain). Dept. of Inorganic Chemistry

    2007-10-15

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism.

  2. Lubrication in tablet formulations.

    Science.gov (United States)

    Wang, Jennifer; Wen, Hong; Desai, Divyakant

    2010-05-01

    Theoretical aspects and practical considerations of lubrication in tablet compression are reviewed in this paper. Properties of the materials that are often used as lubricants, such as magnesium stearate, in tablet dosage form are summarized. The manufacturing process factors that may affect tablet lubrication are discussed. As important as the lubricants in tablet formulations are, their presence can cause some changes to the tablet physical and chemical properties. Furthermore, a detailed review is provided on the methodologies used to characterize lubrication process during tablet compression with relevant process analytical technologies. Finally, the Quality-by-Design considerations for tablet formulation and process development in terms of lubrication are discussed.

  3. Correlation between microbial community and granule conductivity in anaerobic bioreactors for brewery wastewater treatment

    DEFF Research Database (Denmark)

    Shrestha, Pravin; Malvankar, Nikhil S.; Werner, Jeffrey

    2014-01-01

    granules from an aerobic bioreactor designed for phosphate removal were not. There was a moderate correlation (r = 0.67) between the abundance of Geobacter species in the UASB granules and granule conductivity, suggesting that Geobacter contributed to granule conductivity. These results, coupled...

  4. Phase transition time delays in irradiated superheated superconducting granules

    CERN Document Server

    Abplanalp, M; Czapek, G; Diggelmann, U; Furlan, M; Gabutti, A; Janos, S; Moser, U; Pozzi, R; Pretzl, Klaus P; Schmiemann, K; Perret-Gallix, D; Van den Brandt, B; Konter, J A; Mango, S

    1994-01-01

    The time difference between a particle interaction in a Superheated Superconducting Granule (SSG) and the resulting phase transition signal has been explored. Detectors containing Zn and Sn SSG were irradiated with neutrons and protons to study the heating mechanism taking place in nuclear recoil and ionizing events. Scattered neutrons have been detected by a scintillator hodoscope behind the SSG with a recoil energy measurement resolution of 10\\% and an interaction time resolution of 1ns. The fast transition of the metastable granules allowed to determine the elapsed time between an energy deposition and the phase transition signal. In the case of Sn granules, the results show that the time distributions are narrow and independent of the deposited energy in nuclear recoil and ionizing events. In Zn, however, the time distributions are much broader and depend on the energy deposition in the granule.

  5. Treatment of hyper-granulated limb wounds in horses

    Directory of Open Access Journals (Sweden)

    O. A. Bader

    2011-01-01

    Full Text Available This study was performed to investigate the different methods of treating hyper granulation tissue on experimentally induced wounds in equine limbs. Wounds were induced by removal of a skin patch and subcutaneous tissue for about 5-7 cm width and 6-8 cm in length from the dorsal and lateral aspect of the fore and hind limbs below the carpal and tarsal joints. The wounds were left open without treatment and the animals were trained 2-2.5 hours every day for about 3-5 weeks until hyper granulation tissue was developed. The schedule for the treatment of hyper granulation was divided into five groups each contained eight wounds of hyper granulation tissue; each main group was divided into two subgroups. The subgroups of first, second, third, fourth and fifth groups were treated by the following schedules: bandage alone; copper sulphate ointment 10%; silver nitrate ointment 2%; red mercury ointment 11%; and laser therapy (at a total dose of 9.72 Joule / cm2 respectively. While the second subgroups were treated by surgical resection of the hyper granulation tissue, followed by the same treatments applied on the first subgroup. The bandage for all experimental groups was changed every 48 hours until healing was occurred. The clinical and histological observation of the first group revealed that the healing take long period comparing with other groups. The mean of wound healing were 65 days in non surgical removal of hyper granulation tissue subgroup, while 57 days in surgical removed of hyper granulation tissue subgroup. The results of the second, third, fourth groups revealed that the caustic material especially red mercury has a role in healing processes through depressing the hyper granulation tissue. The mean of wound healing of the second group was 42.25 days in non surgical removal of hyper granulation tissue subgroup while 37.25 days in surgically removed hyper granulation tissue subgroup. In the third group the mean of wound healing was 45

  6. Heterogeneity of secretory granules of silent pituitary adenomas

    DEFF Research Database (Denmark)

    Holck, S; Wewer, U M; Albrechtsen, R

    1988-01-01

    Silent pituitary adenomas were compared with hormonally active tumors taking into account the size, number, and ultrastructural characteristics of secretory granules (SG). The study group (a total of 79 primary pituitary adenomas) comprised 27 silent, 21 growth hormone (GH)-producing-, 16 prolactin...... (PRL)-producing-, 5 GH-PRL-producing- and 10 adrenocorticotropic hormone (ACTH)-producing adenomas. The SG of silent adenomas were significantly smaller than SG in endocrine active adenomas. All hormonally inactive tumors also contained small (mean, 94 nm) specific cytoplasmic granules, designated...... approximately 10 to 50% of the granules in each cell. These granules were not seen in hormonally active tumors and considered therefore diagnostic of silent pituitary adenomas....

  7. In vitro binding of puroindolines to wheat starch granules

    DEFF Research Database (Denmark)

    Sørensen, Helle Aagaard; Darlington, H.F.; Shewry, P.R.

    2001-01-01

    Puroindoline (pin) preparations made from flours of hard and soft wheats contained a mixture of pin-a, 0.19/0.53 alpha -amylase inhibitor, and purothionins. Starch granule preparations from the same cultivars were treated with proteinase to remove surface proteins and incubated with solutions...... of the pin preparations. Binding of pin-a and purothionins but not the 0.19/0.53 inhibitor was observed with no apparent differences between the behavior of the pin preparations or starch granule preparations from hard or soft types. No binding was observed when several other proteins (bovine serum albumin......, total albumins, a commercial preparation of wheat alpha -amylase inhibitors, and barley beta -amylase) were incubated with the starch granules under the same conditions, indicating that in vitro binding can be used to study specific starch granule and protein interactions....

  8. FORMULATION DEVELOPMENT AND IN-VITRO EVALUATION OF SUSTAINED RELEASE MATRIX TABLETS OF SALBUTAMOL SULPHATE

    Directory of Open Access Journals (Sweden)

    AMITAVA GHOSH KOUSHIK SEN GUPTA

    2013-09-01

    Full Text Available ABSTRACT: The objective of the present study was to develop salbutamol sulphate matrix tablets, sustained release dosage form, for the treatment of Chronic Obstructive Pulmonary Disease (COPD. Simultaneous equations were formed to calculate the concentration values of Salbutamol sulphate and drug compatibility study was performed through Infrared spectroscopy. The matrix tablets were prepared by wet granulation method using two hydrophobic polymers such as Ethyl cellulose and Acrycoat S-100 in varying ratios. The granules exhibited satisfactory rheological demeanor. All the seven tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house specifications for tested parameters. The results of formulation F-4 (Ethyl cellulose and Acrycoat in 2:1 ratio could extend the release of Salbutamol sulphate up to 12 hr and was found comparable to marketed sustained release products. Model fitting analysis (Zero order, Higuchi and Korsmeyer-Peppas model for all the formulations were performed and it was seen that all the formulations predominantly follow the Higuchi model. While comparing with the ‘n’ values of all the formulations of Korsmeyer-Peppas model, Fickian/Diffusion controlled release was observed in case of F-4 and F-5, whereas for the other formulations non-Fickian transport was observed.

  9. EPR and optical study of Mn{sup 2+}-doped lithium hydrogen oxalate monohydrate single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Kripal, Ram [Department of Physics, University of Allahabad, Allahabad 211002 (India)]. E-mail: ram_kripal2001@rediffmail.com; Govind, Har [Department of Electronics, Ewing Christian College, Allahabad 211003 (India)]. E-mail: chaurasia_har@yahoo.co.in; Maurya, Manju [Department of Physics, University of Allahabad, Allahabad 211002 (India)

    2007-01-15

    EPR study of Mn{sup 2+}-doped lithium hydrogen oxalate monohydrate single crystals are done at room temperature. The Mn{sup 2+} spin-Hamiltonian parameters are evaluated employing a large number of resonant line positions observed for different orientations of the external magnetic field. The values of g, A, B, D, E and a are 1.9942+/-0.0002, 114+/-2x10{sup -4}, 103+/-2x10{sup -4}, 180+/-2x10{sup -4}, 57+/-2x10{sup -4} and 7+/-1x10{sup -4}cm{sup -1}, respectively. The optical absorption study of the crystal is also done. The observed bands are assigned as transitions from the {sup 6}A{sub 1g}(S) ground state to various excited quartet levels of Mn{sup 2+} ion in a cubic crystalline field. These bands are fitted with four parameters, inter-electronic repulsion parameters (B and C), crystal field parameter (D{sub q}) and Tree's correction ({alpha}). The values found for the parameters are B=814cm{sup -1}, C=2255cm{sup -1}, D{sub q}=780cm{sup -1}, and {alpha}=76cm{sup -1}. On the basis of the data obtained, the surrounding crystalline field and the nature of metal-ligand bonding are discussed.

  10. EPR and optical absorption studies of vanadyl ions in potassium oxalate monohydrate

    Energy Technology Data Exchange (ETDEWEB)

    Kripal, Ram [Department of Physics, University of Allahabad, Allahabad 211002 (India)]. E-mail: ram_kripal2001@rediffmail.com; Maurya, Manju [Department of Physics, University of Allahabad, Allahabad 211002 (India)]. E-mail: mmanju8@yahoo.co.in; Govind, Har [Department of Electronics, Ewing Christian College, Allahabad 211003 (India)

    2007-04-15

    Electron paramagnetic resonance (EPR) studies are reported on vanadyl (VO{sup 2+}) ions in potassium oxalate monohydrate (POM) single crystals at room temperature. The results indicate that the paramagnetic impurity takes up an interstitial site in the lattice. The angular variation of EPR spectra in three mutually perpendicular planes are used to determine the spin Hamiltonian parameters and the values obtained are: g{sub x} =2.0153{+-}0.0002, g{sub y} =1.9489{+-}0.0002, g{sub z} =1.9155{+-}0.0002 and A{sub x} =(63{+-}2)x10{sup -4} cm{sup -1}, A{sub y} =(92{+-}2)x10{sup -4} cm{sup -1}, A{sub z} =(193{+-}2)x10{sup -4} cm{sup -1}. The optical absorption spectrum of VO{sup 2+} ions in the crystal lattice is also studied at room temperature. The characteristic spectrum of the VO{sup 2+} ions has four absorption bands. The band positions are calculated using the energy expressions and compared with the observed values to confirm the transitions. The analysis of the spectrum indicates that the first three bands correspond to d-d transitions and the last band is probably charge transfer band. Crystal field parameter (Dq) and tetragonal parameters (Ds and Dt) are also evaluated. From optical and EPR data various bonding parameters are obtained and nature of bonding in the crystal is discussed.

  11. Structural, Hirshfeld surface and spectroscopic studies of the noncentrosymmetric 1-ethylpiperazinediium pentachloroantimonate (III) monohydrate

    Science.gov (United States)

    Soudani, S.; Zeller, M.; Jelsch, C.; Lefebvre, F.; Ben Nasr, Cherif

    2016-08-01

    1-Ethylpiperazinediium pentachloroantimonate (III) monohydrate, C6H16N2SbCl5·H2O, has been synthesized by the reaction of antimony trioxide (Sb2O3) and 1-ethylpiperazine in an aqueous solution of hydrochloric acid. The structure crystallizes in orthorhombic system, in the non-centrosymmetric space group Pca21 and consists of isolated [C6H16N2]2+ cations, square pyramidal [SbCl5]2- anions and lattice water molecules. Osbnd H⋯Cl hydrogen bonds link the [SbCl5]2- anions and water molecules to form double chains stretching along the [101] direction. The chains in turn are linked to the organic cations via Nsbnd H⋯Cl, Csbnd H⋯Cl, Csbnd H⋯O and Nsbnd H⋯O hydrogen bonds to form a three-dimensional network. This structure presents an example of a general square pyramidal complex ion containing a stereo-chemically active lone pair of electrons. Solid state 13C and 15N CP-MAS NMR spectra are in agreement with the X-ray structure, and vibrational absorption bands were identified by infrared spectroscopy. DFT calculations allowed the attribution of the NMR peaks and IR absorption bands. The interactions variability of the two independent cations and ten chloride atoms is analyzed via Hirshfeld surface analysis.

  12. Mebendazole mesylate monohydrate: a new route to improve the solubility of mebendazole polymorphs.

    Science.gov (United States)

    de Paula, Karina; Camí, Gerardo E; Brusau, Elena V; Narda, Griselda E; Ellena, Javier

    2013-10-01

    Mebendazole mesylate monohydrate, a new stable salt of mebendazole (MBZ), has been synthesized and fully characterized. It was obtained from recrystallization of MBZ forms A, B, or C in diverse solvents with the addition of methyl sulfonic acid solution. The crystal packing is first organized as a two-dimensional array consisting of rows of alternating MBZ molecules linked to columns of mesylate ions by hydrogen bonds. The three-dimensional structure is further developed by classical intermolecular interactions involving water molecules. In addition, nonclassical contacts are also found. The vibrational behavior is consistent with the crystal structure, the most important functional groups showing shifts to lower or higher frequencies in relation to the MBZ polymorphs. Thermal analysis indicates that the compound is stable up to 50°C. Decomposition occurs in five steps. Solubility studies show that the title compound presents a significant higher performance than polymorph C. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:3528-3538, 2013.

  13. The electronic structure of alloxan monohydrate. Spectroscopic and density functional synergic approach

    Science.gov (United States)

    Elroby, Shaaban A.; Aziz, Saadullah G.; Hilal, Rifaat H.

    2017-02-01

    In the present communication, quantitative interpretation and assignments of the electronic absorption spectra, vibrational and one- and two-dimensional NMR spectra of alloxan, are detailed. A synergic analysis based on DFT and TD-DFT calculations and the experimental findings are performed. Attempt is made to relate these spectral findings to the electronic structure of alloxan. The computed electronic spectrum predicted three well defined bands. Natural transition orbital analysis indicate an intramolecular charge transfer from npπ orbital of the water oxygen atom resulting in the short wavelength nπ* at ∼200 nm. Furthermore, UV-photoabsorption cross section for alloxan and its monohydrate are simulated. The spectrum, composed of 10 excited states, was simulated with the nuclear ensemble approximation, sampling a Wigner distribution with 300 points. The FT-IR spectrum of alloxan, measured in the solid state as KBr pellets is reported and is computed at the DFT/B3LYP/6-311++G** level of theory. All observed vibrations are assigned. The 600 MHz one- and two-dimensional COSY, 1H NMR spectra of alloxan, measured in DMSO, are reported and analyzed and computed theoretically using the GIAO method. Hydrogen-bond interactions are responsible for remarkable downfield shift of 1H NMR peaks for alloxan.

  14. Tuning Ca:P ratio by NaOH from monocalcium phosphate monohydrate (MCPM)

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Chen; Cao, Peng, E-mail: p.cao@auckland.ac.nz

    2016-09-15

    In this study we report on a continual change of Ca:P ratio in monocalcium phosphate monohydrate (MCPM) by increasing the amount of NaOH added in to the MCPM. The phase identification, chemical compositions, thermal analysis and micro-morphology of the chemically formed powders were characterised with X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), X-ray fluorescence (XRF), thermogravimetric analysis (TGA), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The Ca:P ratio is observed to gradually change from 1.0, which corresponds to dicalcium phosphate dehydrate – DCPD, to stoichiometric 1.67 of apatite. Depending on the attained Ca:P ratio in the powder synthesized in the aqueous solutions, subsequent calcination of these chemically formed powders leads to the formation of various single phasic calcium phosphates or biphasic compounds. It is proposed that the high solubility of MCPM results in fast dissolution and reprecipitation. A multi-step chemical reaction is proposed to elucidate the reaction sequence in the aqueous MCPM−NaOH systems. - Highlights: • Ca:P ratio changes from DCPD to stoichiometric apatite by changing NaOH molarity. • Calcination leads to various mono- or bi-phasic calcium phosphate. • The reaction and phase transformation sequences were investigated.

  15. Growth and characterization of a third order nonlinear optical single crystal: Ethylenediamine-4-nitrophenolate monohydrate

    Energy Technology Data Exchange (ETDEWEB)

    Dhanalakshmi, B. [Department of Physics, Asan Memorial College of Engineering and Technology, Chengalpattu 603 203, Tamil Nadu (India); Ponnusamy, S., E-mail: suruponnus@gmail.com [Center for Materials Science and Nano Devices, Department of Physics, SRM University, Kattankulathur 603 203, Tamil Nadu (India); Muthamizhchelvan, C.; Subhashini, V. [Center for Materials Science and Nano Devices, Department of Physics, SRM University, Kattankulathur 603 203, Tamil Nadu (India)

    2015-10-15

    Highlights: • EDA4NPH crystal possesses negative nonlinear refractive index. • The crystal exhibits high third-order NLO susceptibility. • Wide transparency of the crystal makes it suitable for NLO applications. • Dielectric studies substantiate the suitability for electro-optic applications. • The crystal possesses suitable mechanical strength for device fabrication. - Abstract: Bulk crystals of the charge-transfer complex, ethylenediamine-4-nitrophenolate monohydrate, were grown by slow solvent evaporation method from aqueous solution at room temperature. The X-ray diffraction measurements showed that the crystal belongs to centrosymmetric space group C2/c of monoclinic system. The functional groups in the complex were identified using FTIR, FTRaman and FTNMR analyses. The Z-scan measurements revealed the negative nonlinear refractive index of the crystal. The nonlinear absorption coefficient and third order nonlinear optical susceptibility calculated from the measurements were −3.5823 × 10{sup −3} cm/W and 2.3762 × 10{sup −6} esu respectively. The crystal was shown to be highly transparent above 366 nm by UV–vis spectroscopy and a yellow fluorescence was observed from PL spectrum. The TG–DTA and DSC analyses showed that the crystal is thermally stable up to 117.4 °C. The crystals were characterized by dielectric, etching and microhardness studies.

  16. Influence of ageing, grinding and preheating on the thermal behaviour of alpha-lactose monohydrate.

    Science.gov (United States)

    Garnier, S; Petit, S; Mallet, F; Petit, M-N; Lemarchand, D; Coste, S; Lefebvre, J; Coquerel, G

    2008-09-01

    It is shown that the onset temperature and the magnitude of thermal events observed during DSC analyses of alpha-lactose monohydrate can be strongly affected by various treatments such as ageing, manual grinding and preheating (cycle of preliminary dehydration and rehydration). In the case of grinding and preheating, the change of dehydration pathways was further investigated by using a suitable combination of characterization techniques, including X-ray powder diffraction (XRPD) performed with a synchrotron source (allowing an accurate Rietveld analysis), scanning electron microscopy (SEM), laser particle size measurements, FTIR spectroscopy and (1)H NMR for the determination of beta-lactose contents in samples. It appeared that the dehydration mechanism is affected not only by a smaller particle size distribution, but also by residual anisotropic lattice distortions and by the formation of surface defects or high energy surfaces. The fusion-recrystallization process occurring between anhydrous forms of alpha-lactose at ca. 170 degrees C is not significantly affected by grinding, whereas a preheating treatment induces an unexpected large increase of the enthalpy associated with this transition. Our observations and interpretations confirm the important role of water molecules in the crystal cohesion of the title compound and illustrate the necessity to consider the history of each sample for a satisfactory understanding of the physical properties and the behaviour of this important pharmaceutical excipient.

  17. The bulk crystallization of alpha-lactose monohydrate from aqueous solution.

    Science.gov (United States)

    Raghavan, S L; Ristic, R I; Sheen, D B; Sherwood, J N

    2001-07-01

    The bulk crystallization of alpha-lactose monohydrate from aqueous solution by primary nucleation has been studied under controlled conditions of supersaturation, temperature, and pH. The induction times to nucleation were extremely long compared with those generally observed for other materials, even at the high supersaturations used in the experiment. As a result, it was necessary to stir the supersaturated solution vigorously to induce nucleation in a reasonable but still lengthy working time. Even then, nucleation only occurred to a limited extent, following which growth ceased for 8-10 h before resuming. After this period, growth recommenced but again slowed to a low rate after another 8 h. At this stage, the yield of product was low and in most cases the particles had achieved sizes close to the maximum noted. The yields increased with further crystallization time (22-72 h total from the recommencement of growth) to give, under high initial supersaturation conditions, amounts of product close to the theoretical value. For the most part, however, the particle size did not increase with this later increase in yield, showing only significant changes after the extremely long total crystallization times. It is proposed that these extreme properties result from the formation in solution by mutarotation of the anomer alpha-lactose, which inhibits nucleation as well as its previously observed influence on growth.

  18. In situ investigation of growth rates and growth rate dispersion of α-lactose monohydrate crystals

    Science.gov (United States)

    Dincer, T. D.; Ogden, M. I.; Parkinson, G. M.

    2009-02-01

    The growth rates and growth rate dispersion (GRD) of four different faces of α-lactose monohydrate crystal were measured at 30, 40 and 50 °C in the relative supersaturation range 0.55-2.33 in aqueous solutions. The overall growth rate of the crystal is around 50-60% of the (0 1 0) face of the crystal. The power law was applied to the growth rates of the four faces and the activation energies were calculated to be between 9.5 and 13.7 kcal/mol. This indicates a diffusion-controlled growth, but the exponents calculated are between 2.5 and 3.1 which are higher than unity. Introduction of critical supersaturation decreased the exponents to between 1.8 and 2.4. The variance of GRD for the (0 1 0) face is twice the variance of the GRD of the (1 1 0) and (1 0 0) faces and 10 times higher than the (1 1¯ 1¯) face at the same supersaturations and temperatures. The GRD of the four faces were similar when expressed as a function of growth rate. However, the (0 1 1) face displayed lower GRD than the other faces at the same temperatures and supersaturations.

  19. Spectroscopic Manifestation of Vibrationally-Mediated Structure Change in the Isolated Formate Monohydrate

    Science.gov (United States)

    Denton, Joanna K.; Wolke, Conrad T.; Gorlova, Olga; Gerardi, Helen; McCoy, Anne B.; Johnson, Mark

    2016-06-01

    The breadth of the OH stretching manifold observed in the IR for bulk water is commonly attributed to the thermal population of excited states and the presence of many configurations within the water network. Here, I use carboxylate species as a rigid framework to isolate a single water molecule in the gas phase and cold ion vibrational pre-dissociation spectroscopy to explore excited state contributions to bandwidth. The spectrum of the carboxylate monohydrate exhibits a signature series of peaks in the OH stretching region of this system, providing an archetypal model to study vibrationally adiabatic mode separation. Previous analysis of this behavior accounts for the extensive progression in a Franck-Condon formalism involving displaced vibrationally adiabatic potentials. In this talk I will challenge this prediction by using isotopic substation to systematically change the level structure within these potentials. This picture quantitatively accounts for the diffuse spectrum of this complex at elevated temperature providing a convenient spectroscopic reporter for the temperature of ions in a trap. E. M. Myshakin, K. D. Jordan, E. L. Sibert III, M. A. Johnson J. Chem. Phys. 119, 10138 (2003) W.H. Robertson, et al. J. Phys Chem. 107, 6527 (2003)

  20. Effectiveness of carbocysteine lysine salt monohydrate on models of airway inflammation and hyperresponsiveness.

    Science.gov (United States)

    Asti, C; Melillo, G; Caselli, G F; Daffonchio, L; Hernandez, A; Clavenna, G; Omini, C

    1995-06-01

    We investigated the possible effects of the mucoactive drug Carbocysteine lysine salt monohydrate (CLS.H2O) on experimentally-induced airway inflammation and hyperresponsiveness. CLS.H2O given by the oral route (300 mg kg(-1)) significantly reduced neutrophil infiltration into the airway lumen induced by intratracheal injection of IL-1 beta in rats. In addition, CLS.H2O inhibited dose-dependently (100-300 mg kg(-1) p.o.) the formation of pleural exudate and leukocyte recruitment induced by intrapleural injection of carrageenan in rats. Because of the close interaction between the inflammatory process and the development of airway hyperresponsiveness we also tested CLS.H2O on cigarette-smoke-induced inflammation and hyperreactivity in anaesthetized guinea-pigs. The drug, given either by oral (300 mg kg(-1)) or aerosol route (30-100 mg ml(-1)), was able to reduce the increase in airway responsiveness induced by smoke and the associated cell recruitment detected in the bronchoalveolar lavage (BAL) fluids. These results suggest that CLS.H2O can exert an anti-inflammatory action in addition to its mucoregulatory activity. The anti-inflammatory and anti-hyperreactivity effect of the drug within the airways may be of advantage in the treatment of inflammatory lung diseases where mucus secretion together with airway inflammation and hyperreactivity contribute to airway obstruction.

  1. Carbocysteine lysine salt monohydrate (SCMC-LYS) is a selective scavenger of reactive oxygen intermediates (ROIs).

    Science.gov (United States)

    Brandolini, Laura; Allegretti, Marcello; Berdini, Valerio; Cervellera, Maria Neve; Mascagni, Patrizia; Rinaldi, Matteo; Melillo, Gabriella; Ghezzi, Pietro; Mengozzi, Manuela; Bertini, Riccardo

    2003-01-01

    Carbocysteine lysine salt monohydrate (SCMC-Lys) is a well-known mucoactive drug whose therapeutic efficacy is commonly related to the ability of SCMC-Lys to replace fucomucins by sialomucins. The aim of this study was to determine if SCMC-Lys could exert an anti-oxidant action by scavenging reactive oxygen intermediates (ROIs). Our results show that SCMC-Lys proved effective as a selective scavenger of hypochlorous acid (HOCl) and hydroxyl radical (OH.), this effect being related to the reactivity of the SCMC tioether group. The scavenger activity of SCMC-Lys was observed in free cellular system as well as in activated human polymorphonuclear neutrophils (PMNs). SCMC-Lys scavenger activity on HOCl was paralleled by a powerful protection from HOCl-mediated inactivation of alpha1-antitripsin (alpha1-AT) inhibitor, the main serum protease inhibitor. Production of interleukin-(IL-)8, a major mediator of PMN recruitment in inflammatory diseases, is known to be mediated by intracellular OH. SCMC-Lys significantly reduced IL-8 production on stimulated human peripheral blood mononuclear cells (PBMCs) in the same range of concentrations affecting OH. activity. It is concluded that SCMC-Lys could exert, in addition to its mucoactive capacity, an anti-oxidant action, thus contributing to the therapeutic efficacy of SCMC-Lys.

  2. Growth and characterization of new semiorganic nonlinear optical and piezoelectric lithium sulfate monohydrate oxalate single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Harsh [Crystal Lab, Department of Physics & Astrophysics, University of Delhi, Delhi 110007 (India); Sinha, Nidhi [Department of Physics & Electronics, SGTB Khalsa College, University of Delhi, Delhi 110007 (India); Kumar, Binay, E-mail: b3kumar69@yahoo.co.in [Crystal Lab, Department of Physics & Astrophysics, University of Delhi, Delhi 110007 (India)

    2015-04-15

    Highlights: • A new semiorganic single crystal of LSO grown by slow evaporation technique. • Morphological studies of the LSO crystal deduced by BFDH law. • In the UV–vis spectrum wide transparent region and large band gap were found. • SHG is equal to KDP crystal and d{sub 33} was found to be equal to 6pC/N. • Grown crystal belongs to softer category. - Abstract: New semiorganic crystal of lithium sulfate monohydrate oxalate (LSO) for nonlinear application was synthesized by controlled slow evaporation method. The growth rate of various planes of the grown crystal was estimated by morphological study. Single crystal XRD analysis confirmed that the crystal belongs to triclinic lattice with space group P1. High transparency (∼95%) with large band gap (4.57 eV) was analyzed by UV–vis studies. FTIR and Raman spectroscopy were used to identify various functional groups present in the LSO crystal. SHG efficiency was found to be equal to the KDP crystal. Thermal stability (up to 117.54 °C) and melting point (242 °C) of the crystal were studied by TG-DTA. In dielectric measurements, the value of dielectric constant decreases with increase in frequency. Hardness studies confirmed soft nature of crystals. The piezoelectric coefficient was found to be 6pC/N along [0 0 1].

  3. EPR and optical absorption studies of Cu 2+ doped bis (glycinato) Mg (II) monohydrate single crystals

    Science.gov (United States)

    Dwivedi, Prashant; kripal, Ram

    2010-02-01

    Electron paramagnetic resonance (EPR) study of Cu 2+ doped bis (glycinato) Mg (II) monohydrate single crystals is carried out at room temperature. Copper enters the lattice substitutionally and is trapped at two magnetically inequivalent sites. The observed spectra are fitted to a spin-Hamiltonian of rhombic symmetry with the following values of the parameters: Cu 2+ (I), gx = 2.1577 ± 0.0002, gy = 2.2018 ± 0.0002, gz = 2.3259 ± 0.0002, Ax = (87 ± 2) × 10 -4 cm -1, Ay = (107 ± 2) × 10 -4 cm -1, Az = (141 ± 2) × 10 -4 cm -1; Cu 2+ (II), gx = 2.1108 ± 0.0002, gy = 2.1622 ± 0.0002, gz = 2.2971 ± 0.0002, Ax = (69 ± 2) × 10 -4 cm -1, Ay = (117 ± 2) × 10 -4 cm -1and Az = (134 ± 2) × 10 -4 cm -1. The ground state wave function of the Cu 2+ ion in this lattice is evaluated to be predominantly | x2 - y2lbond2 . The g-factor anisotropy is also calculated and compared with the experimental value. With the help of the optical absorption study, the nature of bonding in the complex is discussed.

  4. 2-(4-Hydroxyphenyl-1H-benzimidazol-3-ium chloride monohydrate

    Directory of Open Access Journals (Sweden)

    Jazmin E. González-Padilla

    2013-09-01

    Full Text Available The title molecular salt, C13H11N2O+·Cl−·H2O, crystallizes as a monohydrate. In the cation, the phenol and benzimidazole rings are almost coplanar, making a dihedral angle of 3.18 (4°. The chloride anion and benzimidazole cation are linked by two N+—H...Cl− hydrogen bonds, forming chains propagating along [010]. These chains are linked through O—H...Cl hydrogen bonds involving the water molecule and the chloride anion, which form a diamond core, giving rise to the formation of two-dimensional networks lying parallel to (10-2. Two π–π interactions involving the imidazolium ring with the benzene and phenol rings [centroid–centroid distances = 3.859 (3 and 3.602 (3 Å, respectively], contribute to this second dimension. A strong O—H...O hydrogen bond involving the water molecule and the phenol substituent on the benzimidazole unit links the networks, forming a three-dimensional structure.

  5. Growth and characterization of new semi-organic L-proline strontium chloride monohydrate single crystals

    Science.gov (United States)

    Gupta, Manoj K.; Sinha, Nidhi; Kumar, Binay

    2011-01-01

    The present communication deals with the synthesis, single crystal growth and characterization of a new nonlinear optical material L-proline strontium chloride monohydrate ( L-PSCM). Single crystals have been grown using the slow solvent evaporation technique. Single crystal XRD analysis confirmed that the crystal belongs to the orthorhombic structure with lattice parameter a=6.6966(3) Å, b=12.4530(5) Å, c=15.2432(5) Å and space group P2 12 12 1. Presence of various functional groups in L-PSCM and protonation of the ions were confirmed by Fourier transform infrared spectroscopy (FT-IR) analysis. The melting point of the single crystal was found to be 126 °C using DSC. Ultraviolet-visible spectral analyses showed that the crystal has low UV cut-off at 226 nm combined with very good transparency of 90% in a wide range. The optical band gap was estimated to be 5.82 eV. Capacitance and dielectric-loss measurements were carried out at different temperatures in the frequency range 1 kHz-2 MHz. The dielectric constant and loss factor were found to be 21 and 0.03 at 1 kHz at room temperature, respectively. Microhardness mechanical studies show that hardness number ( Hv) increases with load for L-PSCM single crystals the by Vickers microhardness method. Second harmonic generation (SHG) efficiency was found to be 0.078 times the value of KDP.

  6. Solid-State Characterization and Interconversion of Recrystallized Amodiaquine Dihydrochloride in Aliphatic Monohydric Alcohols.

    Science.gov (United States)

    Sirikun, Wiriyaporn; Chatchawalsaisin, Jittima; Sutanthavibul, Narueporn

    2016-04-01

    Amodiaquine dihydrochloride monohydrate (AQ-DM) was obtained by recrystallizing amodiaquine dihydrochloride dihydrate (AQ-DD) in methanol, ethanol, and n-propanol. Solid-state characterization of AQ-DD and AQ-DM was performed using X-ray powder diffractometry, Fourier transform infrared spectroscopy, thermogravimetry, and differential scanning calorimetry. All recrystallized samples were identified as AQ-DM. Crystal habits of AQ-DD and AQ-DM were shown to be needle-like and rhombohedral crystals, respectively. When AQ-DD and AQ-DM were exposed to various relative humidity in dynamic vapor sorption apparatus, no solid-state interconversion was observed. However, AQ-DM showed higher solubility than AQ-DD when exposed to bulk water during solubility study, while excess AQ-DM was directly transformed back to a more stable AQ-DD structure. Heating AQ-DM sample to temperatures ≥190°C induced initial change to metastable amorphous form (AQ-DA) which was rapidly recrystallized to AQ-DD upon ≥80%RH moisture exposure. AQ-DD was able to be recrystallized in alcohols (C1-C3) as AQ-DM solid-state structure. In summary, AQ-DM was shown to have different solubility, moisture and temperature stability, and interconversion pathways when compared to AQ-DD. Thus, when AQ-DM was selected for any pharmaceutical applications, these critical transformation and property differences should be observed and closely monitored.

  7. Development of granules from Phyllanthus niruri spray-dried extract

    Directory of Open Access Journals (Sweden)

    Tatiane Pereira de Souza

    2009-12-01

    Full Text Available The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility indexes suitable for a solid dosage form. The compression behavior showed plastic and fragmentary deformation for granules produced by the dry granulation technique and predominantly plastic deformation for wet granulation. Concerning the humidity sorption, the study showed that granules absorb less humidity than the spray-dried extract. However, granules with Eudragit® E 100 were the least hygroscopic.O objetivo deste estudo foi desenvolver grânulos de extrato Phyllantus niruri seco por aspersão e por granulação úmida e avaliar técnicas que possibilitem a produção de grânulos com características tecnológicas e rendimentos aperfeiçoados. Os grânulos foram caracterizados por granulometria, parâmetros reológicos, compressão e comportamento higroscópico. Independentemente da técnica de granulação, os grânulos tecnologicamente desenvolvidos apresentaram diâmetro de partículas, densidades aparente e compactada e índices de compressibilidade adequados para a formulação sólida. O comportamento de compressão mostrou deformação plástica e elástica para os grânulos produzidos por técnicas de granulação seca e, predominantemente, deformação plástica para a granulação úmida. Com relação à absorção da umidade, o estudo mostrou que os grânulos absorvem menos umidade do que o extrato seco por aspersão. Entretanto, os grânulos com Eudragit E 100 foram os menos higroscópicos.

  8. Fluidization of wet granulates under shear.

    Science.gov (United States)

    Rahbari, S H Ebrahimnazhad; Vollmer, J; Herminghaus, S; Brinkmann, M

    2010-12-01

    Small amounts of a wetting liquid render sand a stiff and moldable material. The cohesive forces between the sand grains are caused by capillary bridges at the points of contact. Due to the finite strength of these bridges wet sand undergoes a transition from an arrested (i.e., solidified) to a fluidized state under an externally applied shear force. The transition between these two dynamic states is studied in a MD-type simulation of a two-dimensional assembly of bidisperse frictionless disks under the action of a cosine force profile. In addition to soft core repulsion the disks interact through a hysteretic and short ranged attractive force modeling the effect of the capillary bridges. In this model the transition between the fluidized and the arrested state is discontinuous and hysteretic. The parameter dependence of the critical force for solidification is modeled by combining theoretical arguments with a detailed numerical exploration of the transition. We address a range of densities from slightly below close packing until slightly above densities where the system approaches a shear-banded state. Differences and similarities of the transition in wet granulates to the jamming transition are also addressed.

  9. Giant arachnoid granulation mimicking dural sinus thrombosis.

    Science.gov (United States)

    Ayaz, Ercan; Atalay, Basak; Baysal, Begumhan; Senturk, Senem; Aslan, Ahmet

    2017-01-01

    Arachnoid granulations (AG) are composed of dense, collagenous connective tissue that includes clusters of arachnoid cells. They tend to invaginate into the dural sinuses, through which cerebrospinal fluid enters the venous system. AG are most commonly seen at the junction between the middle and lateral thirds of the transverse sinuses near the entry sites of the superficial veins. Presently described is the case of a 21-year-old female who presented at the clinic with recurrent headaches. Magnetic resonance (MR) imaging revealed a 3.5-cm lesion, which extended from confluens sinuum through the superior sagittal sinus. The lesion had created a scallop-shaped area of erosion in the neighboring occipital bone. To exclude sinus thrombosis, MR venography was performed, which displayed a maintained venous flow around the lesion. Headaches were treated symptomatically with medical therapy. Giant AG can be misdiagnosed as dural sinus thrombosis. MR imaging combined with MR venography is the most useful diagnostic tool to differentiate giant AG from dural sinus thrombosis.

  10. Brain Herniation into Giant Arachnoid Granulation: An Unusual Case

    Science.gov (United States)

    Santos, Gonçalo Roque

    2017-01-01

    Arachnoid granulations are structures filled with cerebrospinal fluid (CSF) that extend into the venous sinuses through openings in the dura mater and allow the drainage of CSF from subarachnoid space into venous system. Usually they are asymptomatic but can be symptomatic when large enough to cause sinus occlusion. We report a rare case of a brain herniation into a giant arachnoid granulation in an asymptomatic elderly male patient, which was discovered incidentally. PMID:28392955

  11. Preparation of Glass Ceramic Based on Granulated Slag and Cullet

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The glass-ceramic was prepared on the basis of materials of granulated slag containing high-calcium oxide and cullet.The content of granulated slag ranges from 50%-60%wt in the glass compositions. The samples were analyzed by DTA, SEM and XRD.The results show that the main crystal phase of the glass-ceramic is β-CaSiO3,Which is in scattering fiber or column form.The applying properties have also been measured.

  12. Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum

    OpenAIRE

    Parthiv Haldipur; Iswariya Sivaprakasam; Vinod Periasamy; Subashika Govindan; Shyamala Mani

    2015-01-01

    ABSTRACT The plane of division of granule neuron progenitors (GNPs) was analysed with respect to the pial surface in P0 to P14 cerebellum and the results showed that there was a significant bias towards the plane of cell division being parallel to pial surface across this developmental window. In addition, the distribution of β-Catenin in anaphase cells was analysed, which showed that there was a significant asymmetry in the distribution of β-Catenin in dividing GNPs. Further, inhibition of S...

  13. Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum.

    Science.gov (United States)

    Haldipur, Parthiv; Sivaprakasam, Iswariya; Periasamy, Vinod; Govindan, Subashika; Mani, Shyamala

    2015-05-15

    The plane of division of granule neuron progenitors (GNPs) was analysed with respect to the pial surface in P0 to P14 cerebellum and the results showed that there was a significant bias towards the plane of cell division being parallel to pial surface across this developmental window. In addition, the distribution of β-Catenin in anaphase cells was analysed, which showed that there was a significant asymmetry in the distribution of β-Catenin in dividing GNPs. Further, inhibition of Sonic Hedgehog (Shh) signalling had an effect on plane of cell division. Asymmetric distribution of β-Catenin was shown to occur towards the source of a localized extracellular cue.

  14. Prevention of chloridazon and metribuzin pollution using lignin-based formulations.

    Science.gov (United States)

    Fernández-Pérez, Manuel; Villafranca-Sánchez, Matilde; Flores-Céspedes, Francisco; Pérez-García, Susana; Daza-Fernández, Isabel

    2010-05-01

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in lignin-based granules with different sizes to obtain controlled release formulations (CRFs) and reduce water pollution risk. Kinetics release tests in water and soil showed that the release rate of both from CRFs diminished in comparison to technical products. A linear correlation was obtained between the time taken for 50% of the active ingredient to be released (T(50)) into water and granule size of the CRFs. Besides, a linear correlation was reached between T(50) values in water and soil. Mobility experiments carried out in calcareous soil show that the use of lignin-based CRFs reduces the presence of both herbicides in the leachate compared to the technical grade products. The set of experiments developed in this research can be useful to design, prepare and evaluate formulations with CR properties which can reduce the pollution derived from the use of herbicides.

  15. Preventive effect of Ganfujian granule on experimental hepatocarcinoma in rats

    Institute of Scientific and Technical Information of China (English)

    Yan Qian; Chang-Quan Ling

    2004-01-01

    AIM: To investigate the inhibitory effect of dietary and medicinal formula Ganfujian granule on diethylnitrosamine (DEN)-induced hepatocarcinoma in rats.METHODS: Male SD rats had free access to water containing 0.1 g/L DEN for 16 weeks, during which the rats fed with standard diet or administration of Ganfujian granule (30.4 g/Kg in diet). At weeks 4, 8, 12 and 16 of hepatocarcinogenesis 5 rats of each group were sacrificed, and at week 20 another 30 rats were sacrificed from each group. The end point for survival observation was at week 28.Immunochemistry methods were used to examine the effect of Ganfujian granule on the process of hepatocarcinogenesis including proliferation of hepatocytes and cell cycle modulation.RESULTS: Ganfujian granule could reduce and delay the incidence of hepatocarcinoma in rats and prolong the survival of animals. In addition, Ganfujian granule had a marked inhibitory effect on high expression of cyclin dependent kinase (CDK4) during the whole process of hepatocarcinogenesis and cyclin D1 at week 16 and the number of proliferating cell nuclear antigen (PCNA) positive cells in different stages of hepatocarcinogenesis.CONCLUSION: Ganfujian granule can reduce and delay the incidence of hepatocarcinoma in rats by exerting direct or indirect effects on cell cycle and inhibiting uncontrolled proliferation of hepatocytes.

  16. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

    OpenAIRE

    Kayentao Kassoum; Doumbo Ogobara K; Pénali Louis K; Offianan André T; Bhatt Kirana M; Kimani Joshua; Tshefu Antoinette K; Kokolomami Jack HT; Ramharter Michael; de Salazar Pablo Martinez; Tiono Alfred B; Ouédraogo Alphonse; Bustos Maria Dorina G; Quicho Frederick; Borghini-Fuhrer Isabelle

    2012-01-01

    Abstract Background Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to 90% (P 3 times the upper limit of normal (ULN) and peak total bilirubin >2xULN (i.e. within the Hy’s law definition). Conclusions The pyron...

  17. Twin screw wet granulation: the study of a continuous twin screw granulator using Positron Emission Particle Tracking (PEPT) technique.

    Science.gov (United States)

    Lee, Kai T; Ingram, Andy; Rowson, Neil A

    2012-08-01

    In this paper, Positron Emission Particle Tracking (PEPT) techniques are utilised to track the trajectory of single particles through the mixing and conveying zones of a Twin Screw Granulator (TSG). A TSG consisting of conveying zones and mixing zones is used in this study. The mixing zones are arranged with kneading discs at an angle of 30°, 60° or 90°. Experiments were carried out using different mixing configurations with various screw speed and total mass flow rate. The PEPT data obtained were then utilised to obtain the residence time distribution (RTD) and the Peclet number in an attempt to gain some insight into the mixing of the process. The fill level of the granulator was also estimated to study the mechanism of granulation. As might be expected, it was shown that the residence time of the granulation process increases with decreasing screw speed. It also increases with increasing angle of the arrangement of kneading blocks in the mixing zones, but will decreases when powder feed rate is increased. The fill level of the mixing zone in particular increases when the screw speed decreases or when powder feed rate increases. Furthermore, the fill level of the granulator will increase when the mixing zone configuration changes from 30° to 90°. It is shown that the granulator is never fully filled, even using 90° mixer elements implying limited compaction which may explain why the granules produced are porous compared with those from a high shear mixer. Interestingly, the RTD analysis reveals that the extent of axial mixing in the mixing zone of the granulator does not change significantly for different configurations and process conditions. There is evidence of a tail in the RTD which implies some material hold up and channelling.

  18. Impact of screw elements on continuous granulation with a twin-screw extruder.

    Science.gov (United States)

    Djuric, Dejan; Kleinebudde, Peter

    2008-11-01

    The influence of different screw element types on wet granulation process with a twin-screw extruder was investigated. Lactose granules were prepared with different screw configurations such as conveying, combing mixer and kneading elements. The use of kneading blocks led to an almost complete agglomeration of lactose, whereas kneading and combing mixer elements resulted in smaller granules in comparison. Granule porosity varied between 17.4% and 50.6%. Granule friability values ranged from 1.2% to 38.5%. Conveying elements led to the most porous and friable granules, whereas kneading blocks produced the densest and least friable granules. Combing mixer elements produced granules with median properties. A linear correlation between granule porosity and the natural logarithm of granule friability was detected. Flowability of granules was also influenced by the element type. Compressed granules with higher granule porosities resulted in tablets with higher tensile strength values and vice versa. Twin-screw extruders proved to be a versatile tool for wet granulation. By the choice of a suitable screw element granule and tablet characteristics were influenced.

  19. Assignment of the lowest-lying THz absorption signatures in biotin and lactose monohydrate by solid-state density functional theory

    Science.gov (United States)

    Allis, D. G.; Fedor, A. M.; Korter, T. M.; Bjarnason, J. E.; Brown, E. R.

    2007-06-01

    The narrow terahertz (THz) features in crystalline biotin and lactose monohydrate observed in recent experimental studies are considered by solid-state density functional theory (DFT) calculations. The lowest-frequency THz features in both solid-state biotin and lactose monohydrate are assigned to external hindered rotational modes and not to the lowest-frequency internal modes predicted from isolated-molecule calculations. The motions of the molecules associated with these narrow THz features and the interactions between molecules in the hydrogen-bonded networks of these molecular crystals are discussed, and comparisons are made to similar studies on molecular crystals not exhibiting strong intermolecular interactions.

  20. Comparison of novel granulated pellet-containing tablets and traditional pellet-containing tablets by artificial neural networks.

    Science.gov (United States)

    Huang, Ying; Yao, Qinghe; Zhu, Chune; Zhang, Xuan; Qin, Lingzhen; Wang, Qinruo; Pan, Xin; Wu, Chuanbin

    2015-01-01

    Novel granulated pellets technique was adopted to prepare granulated pellet-containing tablets (GPCT). GPCT and traditional pellet-containing tablets (PCT) were prepared according to 29 formulations devised by the Design Expert 7.0, with doxycycline hydrochloride as model drug, blends of Eudragit FS 30D and Eudragit L 30D-55 as coating materials, for the comparison study to confirm the superiority of GPCT during compaction. Eudragit FS 30D content, coating weight gain, tablet hardness and pellet size were chosen as influential factors to investigate the properties and drug release behavior of tablets. The correlation coefficients between the experimental values and the predicted values by artificial neural networks (ANNs) for PCT and GPCT were 0.9474 and 0.9843, respectively, indicating the excellent prediction of ANNs. The similarity factors (f2) for release profiles of GPCT and the corresponding original pellets were higher than those of PCT, suggesting that the excipient layer of granulated pellets absorbed the compressing force and protected the integrity of coating films during compaction.

  1. Effect of binders on the release rates of direct molded verapamil tablets using twin-screw extruder in melt granulation.

    Science.gov (United States)

    Tan, David Cheng Thiam; Chin, William Wei Lim; Tan, En Hui; Hong, Shiqi; Gu, Wei; Gokhale, Rajeev

    2014-03-10

    Conventional manufacturing of pharmaceutical tablets often involves single processes such as blending, granulation, milling and direct compression. A process that minimizes and incorporates all these in a single continuous step is desirable. The concept of omitting milling step followed by direct-molding of tablets utilizing a twin-screw extruder in a melt granulation process using thermoplastic binders was explored. The objective of this study was to investigate the effect of combining hydrophilic binder (HPMC K4M, PEO 1M), and hydrophobic binder (Compritol® ATO 888, Precirol® ATO 5) on the release profiles of direct-molded tablets and direct-compressed tablets from milled extrudates using a quality-by-design approach. It was identified that hydrophilic binder type and process significantly affects (p=0.005) the release profiles of verapamil. Moreover, two-way interaction analysis demonstrated that the combination of process with type of hydrophilic polymer (p=0.028) and the type of hydrophilic polymer with polymer ratio (p=0.033) significantly affected the release profiles. The formulation release kinetics correlated to Higuchi release model and the mechanism correlated to a non-Fickian release mechanism. The results of the present study indicated that direct-molded tablets with different release profiles can be manufactured without milling process and through a continuous melt granulation using twin-screw extruder with appropriate thermoplastic binder ratio.

  2. Use of a granular bioplastic formulation for carrying conidia of a non-aflatoxigenic strain of Aspergillus flavus.

    Science.gov (United States)

    Accinelli, Cesare; Saccà, M Ludovica; Abbas, Hamed K; Zablotowicz, Robert M; Wilkinson, Jeffery R

    2009-09-01

    Previous research demonstrated that aflatoxin contamination in corn is reduced by field application of wheat grains pre-inoculated with the non-aflatoxigenic Aspergillus flavus strain NRRL 30797. To facilitate field applications of this biocontrol isolate, a series of laboratory studies were conducted on the reliability and efficiency of replacing wheat grains with the novel bioplastic formulation Mater-Bi to serve as a carrier matrix to formulate this fungus. Mater-Bi granules were inoculated with a conidial suspension of NRRL 30797 to achieve a final cell density of approximately log 7 conidia/granule. Incubation of 20-g soil samples receiving a single Mater-Bi granule for 60-days resulted in log 4.2-5.3 propagules of A. flavus/g soil in microbiologically active and sterilized soil, respectively. Increasing the number of granules had no effect on the degree of soil colonization by the biocontrol fungus. In addition to the maintenance of rapid vegetative growth and colonization of soil samples, the bioplastic formulation was highly stable, indicating that Mater-Bi is a suitable substitute for biocontrol applications of A. flavus NRRL 30797.

  3. EPR and optical absorption study of Cu{sup 2+} doped lithium sulphate monohydrate (LSMH) single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Sheela, K. Juliet; Subramanian, P., E-mail: psubramaniangri@gmail.com [Department of Physics, Gandhigram Rural Institute-Deemed University, Gandhigram, Dindigul-624302, Tamilnadu (India); Krishnan, S. Radha; Shanmugam, V. M. [CSIR-Central Electrochemical Research Institute, Karaikudi-63006, Tamilnadu (India)

    2016-05-23

    EPR study of Cu{sup 2+} doped NLO active Lithium Sulphate monohydrate (Li{sub 2}SO{sub 4.}H{sub 2}O) single crystals were grown successfully by slow evaporation method at room temperature. The principal values of g and A tensors indicate existence of orthorhombic symmetry around the Cu{sup 2+} ion. From the direction cosines of g and A tensors, the locations of Cu{sup 2+} in the lattice have been identified as interstitial site. Optical absorption confirms the rhombic symmetry and ground state wave function of the Cu{sup 2+} ion in a lattice as d{sub x2-y2}.

  4. Liposomal paclitaxel formulations.

    Science.gov (United States)

    Koudelka, Stěpán; Turánek, Jaroslav

    2012-11-10

    Over the past three decades, taxanes represent one of the most important new classes of drugs approved in oncology. Paclitaxel (PTX), the prototype of this class, is an anti-cancer drug approved for the treatment of breast and ovarian cancer. However, notwithstanding a suitable premedication, present-day chemotherapy employing a commercial preparation of PTX (Taxol®) is associated with serious side effects and hypersensitivity reactions. Liposomes represent advanced and versatile delivery systems for drugs. Generally, both in vivo mice tumor models and human clinical trials demonstrated that liposomal PTX formulations significantly increase a maximum tolerated dose (MTD) of PTX which outperform that for Taxol®. Liposomal PTX formulations are in various stages of clinical trials. LEP-ETU (NeoPharm) and EndoTAG®-1 (Medigene) have reached the phase II of the clinical trials; Lipusu® (Luye Pharma Group) has already been commercialized. Present achievements in the preparation of various liposomal formulations of PTX, the development of targeted liposomal PTX systems and the progress in clinical testing of liposomal PTX are discussed in this review summarizing about 30 years of liposomal PTX development.

  5. EPR and optical study of Mn{sup 2+} doped monohydrated dipotassium stannic chloride

    Energy Technology Data Exchange (ETDEWEB)

    Kripal, Ram, E-mail: ram_kripal2001@rediffmail.com; Singh, Manju

    2014-11-15

    Highlights: • EPR study of Mn{sup 2+}: DPSC crystal is done at room temperature. • The spin Hamiltonian parameters for two Mn{sup 2+} sites are determined. • The optical absorption study is also done. • The nature of metal–ligand bonding is discussed on the basis of EPR and optical data. • Theoretical zero-field splitting parameters match well with the experimental values. - Abstract: Electron paramagnetic resonance (EPR) study at room temperature (RT) is used to investigate the property of Mn{sup 2+} doped monohydrated dipotassium stannic chloride (K{sub 2}SnCl{sub 4}⋅H{sub 2}O) single crystal. EPR spectra show that there exist two substitutional sites, the spin Hamiltonian parameters for which are determined. The optical absorption study is also done at room temperature in the wavelength range 195–1100 nm. The observed bands are assigned as transitions from {sup 6}A{sub 1g}(S) ground state to various excited states. These bands are fitted with four parameters, namely Racah inter-electronic repulsion parameters B = 792 cm{sup −1}, C = 2278 cm{sup −1}; cubic crystal field splitting parameter Dq = 700 cm{sup −1} and Trees correction α = 76 cm{sup −1}. The nature of metal–ligand bonding is discussed on the basis of EPR and optical data. Superposition model (SPM) is used to find out the crystal field (CF) parameters and the perturbation formulae are used to obtain zero-field splitting (ZFS) parameters. Theoretically calculated ZFS parameters match well with the experimental values obtained from EPR study.

  6. Comparison of creatine monohydrate and carbohydrate supplementation on repeated jump height performance.

    Science.gov (United States)

    Koenig, Chad A; Benardot, Dan; Cody, Mildred; Thompson, Walter R

    2008-07-01

    Creatine monohydrate (CrMH) supplementation aids the ability to maintain performance during repeated bouts of high-intensity exercise, including jump performance. However, carbohydrate supplementation may also provide similar benefits and is less expensive. This study compared the effects of an energy-free placebo, 2 different caloric concentrations of carbohydrate drinks, and a CrMH supplement on repeated jump heights. Sixty active males (mean age, 22 +/- 3.2 years) performed 2 sets of countermovement static jump height tests (10 jumps over 60 seconds) separated by 5 days to determine the differential effects of the placebo, carbohydrate, and CrMH on jump height sustainability over 10 jumps. Subjects were randomly assigned to groups (15 subjects per group) to receive daily doses (x5 days) of carbohydrate drinks containing 100 or 250 kilocalories (kcal), a 25-g CrMH supplement, or an energy-free placebo. After 5 days, the CrMH group experienced a significant weight gain (+1.52; +/-0.89 kg, p energy-free placebo over the final 3-4 jumps. The 250-kcal carbohydrate-supplemented group experienced a level of benefit (p < 0.01) that was at least equal to that of the CrMH group (p < 0.05), suggesting that the higher dose of carbohydrate was as effective as CrMH in maintaining repeated bouts of high-intensity activity as measured by repeated static jumps. Given the equivalent performance improvement and the absence of weight gain, the carbohydrate supplementation could be considered the preferred option for weight-conscious power athletes involved in activities that require repeated- motion high-intensity activities.

  7. Enrofloxacinium citrate monohydrate: Preparation, crystal structure, thermal stability and IR-characterization

    Science.gov (United States)

    Golovnev, Nicolay N.; Vasiliev, Alexander D.; Kirik, Sergei D.

    2012-08-01

    Enrofloxacinium citrate monohydrate (I), CHFNO3+·CHO7-·HO, [C19H22FN3O3 - enrofloxacin, EnrH] has been crystallized from the mutual solution of citric acid and enrofloxacin in ambient conditions. The colorless crystals have been investigated using X-ray single crystal and powder techniques, and characterized by differential scanning calorimetry, thermogravimetry and infrared spectroscopy. The obtained compound can be considered as a salt with enrofloxacinium in the role of a cation and citrate as an anion. The ions ratio equals to 1:1. The compound crystallizes in the triclinic lattice with a = 9.0489(8) Å, b = 9.6531(8) Å, c = 14.913(1) Å, α = 98.813(1)°, β = 92.029(1)°, γ = 91.013(1)°, Z = 2, V = 1286.1(2) Å3, S.G. P1¯. The crystal structure determination reveals the importance of inter- and intramolecular interactions in the crystal formation. The EnrH2+ and HCit molecular ions are packed in alternating layers with water molecules inserted into the citrate layers. A citrate ion in the layer is linked via H-bondings with two adjacent ones and three water molecules. Enrofloxacinium cations are packaged by means of a benched mode and every cation is linked by three intermolecular thymus type H-bondings with nitrogens of adjacent cations and by two links with the oxygen of the citrate ions. The infrared spectra gave the evidence of H-bonding formation in the obtained salt. The π-stacking interactions are observed between the aromatic cycles of the adjacent cations which are located in an antiparallel style in a layer.

  8. Growth and characterization of new semi-organic L-proline strontium chloride monohydrate single crystals

    Energy Technology Data Exchange (ETDEWEB)

    Gupta, Manoj K. [Crystal Lab, Department of Physics and Astrophysics, University of Delhi, Delhi 7 (India); Sinha, Nidhi [Department of Electronics, SGTB Khalsa College, University of Delhi, Delhi 7 (India); Kumar, Binay, E-mail: bkumar@physics.du.ac.i [Crystal Lab, Department of Physics and Astrophysics, University of Delhi, Delhi 7 (India)

    2011-01-01

    The present communication deals with the synthesis, single crystal growth and characterization of a new nonlinear optical material L-proline strontium chloride monohydrate (L-PSCM). Single crystals have been grown using the slow solvent evaporation technique. Single crystal XRD analysis confirmed that the crystal belongs to the orthorhombic structure with lattice parameter a=6.6966(3) A, b=12.4530(5) A, c=15.2432(5) A and space group P2{sub 1}2{sub 1}2{sub 1}. Presence of various functional groups in L-PSCM and protonation of the ions were confirmed by Fourier transform infrared spectroscopy (FT-IR) analysis. The melting point of the single crystal was found to be 126 {sup o}C using DSC. Ultraviolet-visible spectral analyses showed that the crystal has low UV cut-off at 226 nm combined with very good transparency of 90% in a wide range. The optical band gap was estimated to be 5.82 eV. Capacitance and dielectric-loss measurements were carried out at different temperatures in the frequency range 1 kHz-2 MHz. The dielectric constant and loss factor were found to be 21 and 0.03 at 1 kHz at room temperature, respectively. Microhardness mechanical studies show that hardness number (H{sub v}) increases with load for L-PSCM single crystals the by Vickers microhardness method. Second harmonic generation (SHG) efficiency was found to be 0.078 times the value of KDP.

  9. Second prize: Comprehensive proteomic analysis of human calcium oxalate monohydrate kidney stone matrix.

    Science.gov (United States)

    Canales, Benjamin K; Anderson, Lorraine; Higgins, Leeann; Slaton, Joel; Roberts, Ken P; Liu, Nathan; Monga, Manoj

    2008-06-01

    Previous efforts to identify the protein content of stone matrix have been limited by the lack of technology necessary to analyze the highly insoluble protein-crystalline complex. Our study objective is to characterize the matrix of calcium oxalate monohydrate (COM) stones using a comprehensive proteomics approach. Seven pure COM stones were powdered, and proteins were extracted using four different buffer solutions. Detergent cleanup spin columns or concentrators were used to remove detergent and to exchange buffers before trypsin digestion. Tryptic peptides were analyzed with reversed-phase, high-performance liquid chromatography (RP-HPLC) and tandem mass spectrometry (MS/MS) using a QSTAR Pulsar i quadrapole time of flight mass spectrometer. Tandem mass spectra were searched against National Center for Biotechnology Information human nonredundant database using ProteinPilot 1.0 software (Applied Biosystems, Inc.) for protein hits; peptide MS/MS spectra were manually inspected. Of the four buffers, only 2% sodium dodecyl sulfate (SDS) samples had normal HPLC and MS/MS elution patterns. We identified 68 distinct proteins with 95% confidence. More than 50 of the proteins have not been previously identified in stone matrix. Of particular note, a significant number of inflammatory proteins were identified, including immunoglobulins, defensin -3, clusterin, complement C3a, kininogen, and fibrinogen. SDS reducing buffer was efficient at solubilizing proteins from stone matrix for further MS-based proteomic analysis. A variety of cellular, structural, and plasma proteins comprise COM stone matrix. Several of the stone proteins are involved in cell injury pathways, which suggests that inflammation plays a role in human COM stone formation.

  10. Calcium oxalate monohydrate crystals internalized into renal tubular cells are degraded and dissolved by endolysosomes.

    Science.gov (United States)

    Chaiyarit, Sakdithep; Singhto, Nilubon; Thongboonkerd, Visith

    2016-02-25

    Interaction between calcium oxalate crystals and renal tubular cells has been recognized as one of the key mechanisms for kidney stone formation. While crystal adhesion and internalization have been extensively investigated, subsequent phenomena (i.e. crystal degradation and dissolution) remained poorly understood. To explore these mechanisms, we used fluorescein isothiocyanate (FITC)-labelled calcium oxalate monohydrate (COM) crystals (1000 μg/ml of crystals/culture medium) to confirm crystal internalization into MDCK (Type II) renal tubular cells after exposure to the crystals for 1 h and to trace the internalized crystals. Crystal size, intracellular and extracellular fluorescence levels were measured using a spectrofluorometer for up to 48 h after crystal internalization. Moreover, markers for early endosome (Rab5), late endosome (Rab7) and lysosome (LAMP-2) were examined by laser-scanning confocal microscopy. Fluorescence imaging and flow cytometry confirmed that FITC-labelled COM crystals were internalized into MDCK cells (14.83 ± 0.85%). The data also revealed a reduction of crystal size in a time-dependent manner. In concordance, intracellular and extracellular fluorescence levels were decreased and increased, respectively, indicating crystal degradation/dissolution inside the cells and the degraded products were eliminated extracellularly. Moreover, Rab5 and Rab7 were both up-regulated and were also associated with the up-regulated LAMP-2 to form large endolysosomes in the COM-treated cells at 16-h after crystal internalization. We demonstrate herein, for the first time, that COM crystals could be degraded/dissolved by endolysosomes inside renal tubular cells. These findings will be helpful to better understand the crystal fate and protective mechanism against kidney stone formation.

  11. Formulation, Characterization and Physicochemical Evaluation of Ranitidine Effervescent Tablets

    Directory of Open Access Journals (Sweden)

    Abolfazl Aslani

    2013-08-01

    Full Text Available Purpose: The aim of this study was to design, formulate and physicochemically evaluate effervescent ranitidine hydrochloride (HCl tablets since they are easily administered while the elderly and children sometimes have difficulties in swallowing oral dosage forms. Methods: Effervescent ranitidine HCl tablets were prepared in a dosage of 300 mg by fusion and direct compression methods. The powder blend and granule mixture were evaluated for various pre-compression characteristics, such as angle of repose, compressibility index, mean particle size and Hausner's ratio. The tablets were evaluated for post-compression features including weight variation, hardness, friability, drug content, dissolution time, carbon dioxide content, effervescence time, pH, content uniformity and water content. Effervescent systems with appropriate pre and post-compression qualities dissolved rapidly in water were selected as the best formulations. Results: The results showed that the flowability of fusion method is more than that of direct compression and the F5 and F6 formulations of 300 mg tablets were selected as the best formulations because of their physicochemical characteristics. Conclusion: In this study, citric acid, sodium bicarbonate and sweeteners (including mannitol, sucrose and aspartame were selected. Aspartame, mint and orange flavors were more effective for masking the bitter taste of ranitidine. The fusion method is the best alternative in terms of physicochemical and physical properties.

  12. Identification of a major QTL controlling the content of B-type starch granules in Aegilops

    Science.gov (United States)

    Howard, Thomas; Rejab, Nur Ardiyana; Griffiths, Simon; Leigh, Fiona; Leverington-Waite, Michelle; Simmonds, James; Uauy, Cristobal; Trafford, Kay

    2011-01-01

    Starch within the endosperm of most species of the Triticeae has a unique bimodal granule morphology comprising large lenticular A-type granules and smaller near-spherical B-type granules. However, a few wild wheat species (Aegilops) are known to lack B-granules. Ae. peregrina and a synthetic tetraploid Aegilops with the same genome composition (SU) were found to differ in B-granule number. The synthetic tetraploid had normal A- and B-type starch granules whilst Ae. peregrina had only A-granules because the B-granules failed to initiate. A population segregating for B-granule number was generated by crossing these two accessions and was used to study the genetic basis of B-granule initiation. A combination of Bulked Segregant Analysis and QTL mapping identified a major QTL located on the short arm of chromosome 4S that accounted for 44.4% of the phenotypic variation. The lack of B-granules in polyploid Aegilops with diverse genomes suggests that the B-granule locus has been lost several times independently during the evolution of the Triticeae. It is proposed that the B-granule locus is susceptible to silencing during polyploidization and a model is presented to explain the observed data based on the assumption that the initiation of B-granules is controlled by a single major locus per haploid genome. PMID:21227932

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

    Science.gov (United States)

    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.

  14. Aerobic Granulation in Sequencing Batch Reactor (SBR Treating Saline Wastewater

    Directory of Open Access Journals (Sweden)

    Ensieh Taheri

    2012-04-01

    Full Text Available Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 Background and Objectives: Aerobic sludge granulation is an advanced phenomenonin which its mechanisms have not been understood. Granulation can be a promising and novel biological wastewater treatment technology to eliminate organic and inorganic materials in future. High salinity is a parameter which leads to plasmolisatian and reduction of the cell activity. This could be a problem for biological treatment of the saline wastewater. Aerobic granule was formed and investigated during this study. Materials and Methods: This study is an intervention study on the treatment of wastewater with 500-10000 mg/L concentration of NaCl by sequencing batch reactor. Asynthesized wastewater including nutrient required for microorganism's growth was prepared. Input and output pH and EC were measured. Range of pH and DO varied between 7-8, and 2-5 mg/L, respectively. SEM technology was used to identify graduals properties.Results: In terms of color, granules divided into two groups of light brown and black. Granule ranged in 3-7mm with the sediment velocity of 0.9-1.35 m/s and density of 32-60 g/L.Properties of granules were varied. Filamentous bacteria and fungi were dominant in some granules. However non filamentous bacteria were dominant in others. EDX analysis indicated the presence of Ca and PO4.Conclusion: Granules with non filamentous bacterial were compact and settled faster. Presence of different concentrations of salinity leaded to plasmolysis of the bacterial cells and increased concentrations of EPS  in the system as a result  of which granulation accelerated. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso

  15. Preparation of porcelain tile granulates by more environmentally sustainable processes

    Energy Technology Data Exchange (ETDEWEB)

    Gil, C.; Silvestre, D.; Piquer, J.; Garcia-Ten, J.; Quereda, E.; Vicente, M. J.

    2012-07-01

    This study examines the feasibility of manufacturing glazed porcelain tiles with a more environmentally friendly manufacturing process, by reducing water and thermal energy consumption. The process studied in this paper is dry milling in a pendulum mill, with subsequent granulation (in order to obtain a press powder with similar flow ability to that of spray dried powders). The different morphology of the new granulate with respect to the standard spray-dried granulate modifies the microstructure of the green compacts and thus, their behaviour and fired tile properties. In order to obtain porcelain tiles with the required properties (water absorption, mechanical strength,) changes have been made in the raw materials mixture and in the processing variables. Finally, porcelain tiles measuring 50x50 cm have been manufactured at industrial scale with the new granulate using a conventional firing cycle, obtaining quality levels identical to those provided by the spray-dried granulate. These results open the possibility of preparing porcelain tile body compositions through a manufacturing process alternative to the standard one, more environmentally friendly and with lower costs. (Author)

  16. THE KINETICS OF CYTOPLASMIC GRANULE SECRETION IN NATURAL KILLER CYTOTOXICITY

    Institute of Scientific and Technical Information of China (English)

    龚伊红; R.R.Hcrberman; C.W.Reynolds

    1994-01-01

    Antisexum against purified cytoplasmic granules from rat LGL tumor cells, and protein A-gold inmmnoelec-tron microscopy were used to study the secretory events in lysis of YAC-1 tumor cells by rat LGL tumor cells or by isolated LGL from normal rats. After 30 min incubation of effector and target cells together, gold-labeled cyto-plasmic granules were often seen concentrated in the area of the LGL adjacent to the ~ YAC-1 Within 60min,the grantees were observed to move to the cell border near the conjugazed site. At this point, fine granules were fused with file cell membrane, and subsequently released file gold-labeled contents into the junction between the LGL and the target cell. Gold particles could be seen at the B-T interface, on the surface,or sometimes on the target cell surface.These data provide direct evidence for the hypothesis that under conditions of active cytotoxicity,natural killer cells secrete their cytoplasmic granule contents leading to the deposition of granule material on the target cell surface and the eventual lysis of the cell.

  17. Platelet granule exocytosis: A comparison with chromaffin cells

    Directory of Open Access Journals (Sweden)

    Jennifer eFitch-Tewfik

    2013-06-01

    Full Text Available The rapid secretion of bioactive amines from chromaffin cells constitutes an important component of the fight or flight response of mammals to stress. Platelets respond to stresses within the vasculature by rapidly secreting cargo at sites of injury, inflammation, or infection. Although chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release. This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems. Commonalities include the use of transporters to concentrate bioactive amines and other cargos into granules, the role of cytoskeletal remodeling in granule exocytosis, and the use of granules to provide membrane for cytoplasmic projections. The SNAREs and SNARE accessory proteins used by each cell type will also be considered. Finally, we will discuss the newly appreciated role of dynamin family proteins in regulated fusion pore formation. This evaluation of the comparative cell biology of regulated exocytosis in platelets and chromaffin cells demonstrates a convergence of mechanisms between two disparate cell types both tasked with responding rapidly to physiological stimuli.

  18. Massively augmented hippocampal dentate granule cell activation accompanies epilepsy development

    Science.gov (United States)

    Dengler, Christopher G.; Yue, Cuiyong; Takano, Hajime; Coulter, Douglas A.

    2017-01-01

    In a mouse model of temporal lobe epilepsy, multicellular calcium imaging revealed that disease emergence was accompanied by massive amplification in the normally sparse, afferent stimulation-induced activation of hippocampal dentate granule cells. Patch recordings demonstrated reductions in local inhibitory function within the dentate gyrus at time points where sparse activation was compromised. Mimicking changes in inhibitory synaptic function and transmembrane chloride regulation was sufficient to elicit the dentate gyrus circuit collapse evident during epilepsy development. Pharmacological blockade of outward chloride transport had no effect during epilepsy development, and significantly increased granule cell activation in both control and chronically epileptic animals. This apparent occlusion effect implicates reduction in chloride extrusion as a mechanism contributing to granule cell hyperactivation specifically during early epilepsy development. Glutamine plays a significant role in local synthesis of GABA in synapses. In epileptic mice, sparse granule cell activation could be restored by glutamine application, implicating compromised GABA synthesis. Glutamine had no effect on granule cell activation earlier, during epilepsy development. We conclude that compromised feedforward inhibition within the local circuit generates the massive dentate gyrus circuit hyperactivation evident in animals during and following epilepsy development. However, the mechanisms underlying this disinhibition diverge significantly as epilepsy progresses. PMID:28218241

  19. Studi Awal Desain Pabrik Pupuk Organik Granul Dari Organic Waste

    Directory of Open Access Journals (Sweden)

    Zulfatul Hanna

    2015-12-01

    Full Text Available 800x600 Banyak pertanian di Indonesia yang masih bergantung pada penggunaan pupuk kimia. Padahal penggunaan pupuk kimia yang berlebihan dapat menyebabkan penurunan bahan organik tanah. Untuk menyeimbangkannnya saat ini petani juga sedang menggalakkan penggunaan pupuk organik. Sehingga membuat kebutuhan pupuk organik meningkat setiap tahunnya. Pendirian pabrik pupuk organik granul ini dapat memenuhi kebutuhan pupuk organik untuk petani. Prosess pembuatan pupuk organik granul terdiri dari pencampuran bahan baku, yakni sampah organik, kotoran sapi, kotoran domba, dan dipotong dengan rotary knife cutter. Tahap berikutnya adalah proses fermentasi, dengan penambahan bioactivator agar meningkatkan kandungan C-organik, phosphor, dan kalium. Selanjutnya adalah proses granulasi, pembesaran dari partikel dengan proses aglomerasi. Ukuran yang diharapkan pada proses granulasi ini adalah 2-4 mm sehingga produk undersize maupun oversize akan dikembalikan ke dalam granulator setelah melewati screener. Selanjutnya pupuk organik granul dikeringkan. Selanjutnya produk dipisahkan berdasarkan ukurannya lalu didinginkan di Rotary cooler. Setelah keluar dari Rotary Cooler suhu keluaran sekitar 40 oC dan masih mengandung kadar air sebesar 13,7%. Produk dari rotary cooler siap untuk di packaging dan masuk ke dalam pupuk organik granul storage. Dari analisa ekonomi didapatkan BEP sebesar 45% dengan POT sesudah pajak sebesar 4,8 tahun. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4

  20. Asymmetric cell division of granule neuron progenitors in the external granule layer of the mouse cerebellum

    Directory of Open Access Journals (Sweden)

    Parthiv Haldipur

    2015-07-01

    Full Text Available The plane of division of granule neuron progenitors (GNPs was analysed with respect to the pial surface in P0 to P14 cerebellum and the results showed that there was a significant bias towards the plane of cell division being parallel to pial surface across this developmental window. In addition, the distribution of β-Catenin in anaphase cells was analysed, which showed that there was a significant asymmetry in the distribution of β-Catenin in dividing GNPs. Further, inhibition of Sonic Hedgehog (Shh signalling had an effect on plane of cell division. Asymmetric distribution of β-Catenin was shown to occur towards the source of a localized extracellular cue.

  1. Formulations of entomopathogens as bioinsecticides

    Science.gov (United States)

    Developing a proper formulation is a necessary component for commercialization of entomopathogenic microbes as biological insecticides. The objective of this chapter is to present broad-ranging information about formulations to foster research toward developing commercial microbial-based insecticide...

  2. Systematic Equation Formulation

    DEFF Research Database (Denmark)

    Lindberg, Erik

    2007-01-01

    A tutorial giving a very simple introduction to the set-up of the equations used as a model for an electrical/electronic circuit. The aim is to find a method which is as simple and general as possible with respect to implementation in a computer program. The “Modified Nodal Approach”, MNA, and th......, and the “Controlled Source Approach”, CSA, for systematic equation formulation are investigated. It is suggested that the kernel of the P Spice program based on MNA is reprogrammed....

  3. Solution properties and taste behavior of lactose monohydrate in aqueous ascorbic acid solutions at different temperatures: Volumetric and rheological approach.

    Science.gov (United States)

    Sarkar, Abhijit; Sinha, Biswajit

    2016-11-15

    The densities and viscosities of lactose monohydrate in aqueous ascorbic acid solutions with several molal concentrations m=(0.00-0.08)molkg(-1) of ascorbic acid were determined at T=(298.15-318.15)K and pressure p=101kPa. Using experimental data apparent molar volume (ϕV), standard partial molar volume (ϕV(0)), the slope (SV(∗)), apparent specific volumes (ϕVsp), standard isobaric partial molar expansibility (ϕE(0)) and its temperature dependence [Formula: see text] the viscosity B-coefficient and solvation number (Sn) were determined. Viscosity B-coefficients were further employed to obtain the free energies of activation of viscous flow per mole of the solvents (Δμ1(0≠)) and of the solute (Δμ2(0≠)). Effects of molality, solute structure and temperature and taste behavior were analyzed in terms of solute-solute and solute-solvent interactions; results revealed that the solutions are characterized predominantly by solute-solvent interactions and lactose monohydrate behaves as a long-range structure maker.

  4. Synthesis, crystal growth and spectroscopic investigation of novel metal organic crystal: β-Alanine cadmium bromide monohydrate (β-ACBM)

    Science.gov (United States)

    Renugadevi, R.; Kesavasamy, R.

    2014-07-01

    β-Alanine cadmium bromide monohydrate (β-ACBM), a new metal organic crystal has been grown from aqueous solution by slow evaporation technique. The grown crystals have been subjected to single crystal X-ray diffraction analysis to determine the crystal structure. The β-ACBM crystallized in monoclinic system with space group P21/c. The presence of protons and carbons in the β-alanine cadmium bromide monohydrate was confirmed by 1H and 13C nuclear magnetic resonance spectral analysis. The mode of vibration of different molecular groups present in β-ACBM was identified by FT-IR spectral analysis. Transparency of crystals in UV-Vis-NIR region has also been studied. The thermal characteristics of as-grown crystals were analyzed using thermo gravimetric and differential thermal analyses. The magnetic property of the grown crystal was investigated using Vibrating Sample Magnetometer (VSM) at ambient temperature. The mechanical stability of β-ACBM was evaluated by Vickers microhardness measurement.

  5. Synthesis and non linear optical properties of new inorganic-organic hybrid material: 4-Benzylpiperidinium sulfate monohydrate

    Science.gov (United States)

    Kessentini, Yassmin; Ahmed, Ali Ben; Al-Juaid, Salih S.; Mhiri, Tahar; Elaoud, Zakaria

    2016-03-01

    Single crystals of 4-benzyl-piperidine sulfate monohydrate were grown by slow evaporation method at room temperature. The synthesized compound was characterized by means of single-crystal X-ray diffraction, FT-IR and Raman spectroscopy, UV-visible and photoluminescence studies. The title compound crystallises at room temperature in the non centrosymmetric space group P212121.The recorded UV-visible spectrum show good transparency in the visible region and indicates a non-zero value of the first Hyperpolarizability. Photoluminescence spectrum shows a broad and intense band at 440 nm and indicates that the crystal emits blue fluorescence. We also report DFT calculations of the electric dipole moments (μ), Polarizability (α), the static first Hyperpolarizability (β) and HOMO-LUMO analysis of the title compound was theoretically investigated by GAUSSIAN 03 package. The calculated static first Hyperpolarizability is equal to 6.4022 × 10-31 esu. The results show that 4-benzyl-piperidine sulfate monohydrate crystal might have important non linear optical behavior and can be a potential non linear optical material of interest.

  6. The crystal structure, vibrational spectra, thermal behaviour and second harmonic generation of aminoguanidinium(1+) hydrogen L-tartrate monohydrate

    Science.gov (United States)

    Macháčková, Zorka; Němec, Ivan; Teubner, Karel; Němec, Petr; Vaněk, Přemysl; Mička, Zdeněk

    2007-04-01

    Aminoguanidinium(1+) hydrogen L-tartrate monohydrate was prepared by crystallisation from aqueous solution and X-ray structural analysis was carried out. The substance crystallises in the orthorhombic system in space group P2 12 12 1, a = 7.1380(2) Å, b = 9.9700(4) Å, c = 14.0790(6) Å, V = 1001.94(7) Å 3, Z = 4, R = 0.0271 for 2272 observed reflections. The crystal structure consists of a 3D framework formed by hydrogen tartrate anions and water molecules with incorporated aminoguanidinium(1+) cations connected by a system of hydrogen bonds. The FTIR and FT Raman spectra of natural and N,O-deuterated compounds were measured and discussed at laboratory temperature. DSC measurements were carried out in the temperature range from 95 to 380 K. A weak anomaly was observed at a temperature of 268 K. Quantitative measurements of second harmonic generation of powdered aminoguanidinium(1+) hydrogen tartrate monohydrate at 800 nm were performed relative to KDP and a relative efficiency of 14% was observed.

  7. Study of Growth, Structural, Thermal and Nonlinear Optical Properties of Silica Gel Grown Calcium Iodate Monohydrate Crystals

    Directory of Open Access Journals (Sweden)

    Sharda J. Shitole

    2015-12-01

    Full Text Available Single crystals of calcium iodate, monohydrate [Ca (IO32, H2O] were grown by simple gel technique by single and double diffusion method. Morphologies and habit faces like prismatic, prismatic pyramidal, needle shaped, hopper crystals were obtained. Few crystals were opaque, some were translucent and some good quality transparent crystals were obtained. EDAX spectrum verified that crystals are of calcium iodate, monohydrate indeed and was used to find Atomic % and Weight %. Unit cell parameters were obtained from the X-ray diffractogram. The calculated unit cell parameters, β, and‘d’ values are in good agreement with reported ones. Structural analysis was done by using FTIR spectroscopy which confirmed the presence of fundamental infrared frequencies, generally observed in all iodate compounds. Thermal analysis exhibits three steps explicitly on heating the samples. The first step involves dehydration at 5500C, second step shows decomposition at 5800C, and the third step involves again decomposition at 6400C. Powder second harmonic generation experiments exhibit the nonlinear nature of the substance.

  8. Synthesis and molecular structure of the novel monohydrated 3- p-nitrophenylpyrazole derived from 1,3-diketone malonate

    Science.gov (United States)

    Jiménez-Cruz, Federico; Hernández-Ortega, Simón; Ríos-Olivares, Héctor

    2003-05-01

    The synthesis of dimethyl {2-[3-(4-nitrophenyl)-1 H-pyrazol-5-yl]ethyl}malonate monohydrate 1, C 16H 17N 3O 6·H 2O was performed and the molecular structure has been studied by using NMR, single crystal X-ray diffraction and ab initio calculations. The title compound presents a pyrazole ring (N1 to C5), a phenyl ring (C1″ to C6″) attached to C3 and the ethylene dimethyl malonate frame (C1' to C7') attached to C5. The torsion angle defined by N2C3C1″C2″ (-12.26°) showed that pyrazole and phenyl rings are not in the same plane. Monohydration in ( 1) is present in the structure by a NH⋯OH 2 hydrogen bonding, with a bond length of 1.782 Å. Experimental and theoretical evidences indicated the preference of the 3-tautomer over the corresponding 5-tautomer in the titled pyrazole.

  9. A comparative study of the dissolution characteristics of capsule and tablet dosage forms of melt granulations of paracetamol--diluent effects.

    Science.gov (United States)

    Uhumwangho, Michael U; Okor, Roland S

    2007-01-01

    The dissolution characteristics of melt granulations of paracetamol in capsule and tablet dosage form were compared to determine whether the dissolution characteristics of the granules can be actualized by formulating them as rapidly disintegrating tablets. The term melt granulation refers here to the wax-matrix granules that were formed by triturating the drug powder (paracetamol) with a melted carnauba wax. The matrix granules were admixed with diluents (lactose, alpha-cellulose or microcrystalline cellulose) also in granular form to prevent size separation during encapsulation or tableting. The granules were filled into hard gelatin capsules (mean content weight, 500 +/- 6.2 mg) or tableted (mean weight 500 +/- 5.1 mg, and tensile strength 1.36 +/- 0.2 to 1.7 +/- 0.3 MN/m2). The capsules and tablets were subjected to disintegration and in vitro dissolution tests. The dissolution data were analyzed on the basis of zero, first order rate kinetics and Higuchi square root of time relationship. The results showed that the dissolution profiles were generally consistent with a first order rate kinetics (r = 0.95). The first order dissolution rate constants of capsules and tablets of the matrix granules only (without diluents) were 0.31 +/- 0.02 min(-1) and 0.20 +/- 0.03 min(-1), respectively, indicating faster dissolution from the capsules. Therefore, the dissolution characteristics of the matrix particles were not intact after tableting. Addition of diluents to the capsule formulations had no effect on dissolution rates, whereas in the tablets, dissolution rates increased. For instance, inclusion of a diluent up to 50% w/w in the tablets increased the dissolution rate constants to 0.34 +/- 0.04 min(-1) (lactose), 0.42 +/- 0.02 min(-1) (alpha-cellulose), and 0.46 +/- 0.03 min(-1) (microcrystalline cellulose). Thus, alpha-cellulose and microcrystalline cellulose produced greater enhancer effect on the tablet dissolution rates compared to lactose. Both the capsules and

  10. Effects of dietary supplementation with creatine monohydrate during the finishing period on growth performance, carcass traits, meat quality and muscle glycolytic potential of broilers subjected to transport stress

    National Research Council Canada - National Science Library

    Zhang, L; Li, J L; Gao, T; Lin, M; Wang, X F; Zhu, X D; Gao, F; Zhou, G H

    2014-01-01

    ...) creatine monohydrate (CMH) for 14 days. On the morning of 42 day, after an 8-h fast, the birds of CMH-free group were divided into two equal groups, and all birds of these four groups were transported according to the follow protocol...

  11. Solubilities of 2-Naphthalenesulfonic Acid Monohydrate and Sodium 2-Naphthalenesulfonate in Sulfuric Acid Solution and Their Application for Preparing Sodium 2-Naphthalenesulfonate

    Institute of Scientific and Technical Information of China (English)

    张凤宝; 景晖; 朱文宇; 张林; 刘博; 张国亮; 夏清

    2016-01-01

    The solubilities of 2-naphthalenesulfonic acid monohydrate and sodium 2-naphthalenesulfonate in sul-furic acid solutions were measured at temperatures ranging from 278.15 to 338.15 K by using a dynamic method. The concentration of sulfuric acid solution ranged from 0 to 80wt%,. The solubilities of 2-naphthalenesulfonic acid monohydrate and sodium 2-naphthalenesulfonate increased with temperature, and both of them were the lowest at 70wt%, of sulfuric acid solution(03w=0.70)while the highest in pure water. The solubility data were correlated by the modified Apelblat equation. Based on the solubility difference between 2-naphthalenesulfonic acid monohy-drate and sodium 2-naphthalenesulfonate, a new technique in which sodium sulfate was used to replace sodium sulfite in the neutralization reaction was developed. The suitable mole ratio of H2O to Na2SO4 in the neutralization reaction was 80∶1, and that of 2-naphthalenesulfonic acid monohydrate to Na2SO4 was 3.2∶1. The material bal-ance under the suitable mole ratios was given and discussed.

  12. Pyronaridine-artesunate granules versus artemether-lumefantrine crushed tablets in children with Plasmodium falciparum malaria: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kayentao Kassoum

    2012-10-01

    Full Text Available Abstract Background Children are most vulnerable to malaria. A pyronaridine-artesunate pediatric granule formulation is being developed for the treatment of uncomplicated Plasmodium falciparum malaria. Methods This phase III, multi-center, comparative, open-label, parallel-group, controlled clinical trial included patients aged ≤12 years, bodyweight ≥5 to P. falciparum malaria. Patients were randomized (2:1 to pyronaridine-artesunate granules (60/20 mg once daily or artemether-lumefantrine crushed tablets (20/120 mg twice daily, both dosed by bodyweight, orally (liquid suspension for three days. Results Of 535 patients randomized, 355 received pyronaridine-artesunate and 180 received artemether-lumefantrine. Day-28 adequate clinical and parasitological response (ACPR, corrected for re-infection using polymerase chain reaction (PCR genotyping (per-protocol population was 97.1% (329/339; 95% CI 94.6, 98.6 for pyronaridine-artesunate; 98.8% (165/167; 95% CI 95.7, 99.9 for artemether-lumefantrine. The primary endpoint was achieved: pyronaridine-artesunate PCR-corrected day-28 ACPR was statistically significantly >90% (P 3 times the upper limit of normal (ULN and peak total bilirubin >2xULN (i.e. within the Hy’s law definition. Conclusions The pyronaridine-artesunate pediatric granule formulation was efficacious and was non-inferior to artemether-lumefantrine. The adverse event profile was similar for the two comparators. Pyronaridine-artesunate should be considered for inclusion in paediatric malaria treatment programmes. Trial registration ClinicalTrials.gov: identifier NCT00541385

  13. Summary of Granulation Matrix Testing for the Plutonium Immobilization Program

    Energy Technology Data Exchange (ETDEWEB)

    Herman, C.C.

    2001-10-19

    In FY00, a matrix for process development testing was created to identify those items related to the ceramic process that had not been fully developed or tested and to help identify variables that needed to be tested. This matrix, NMTP/IP-99-003, was jointly created between LLNL and SRTC and was issued to all affected individuals. The matrix was also used to gauge the progress of the development activities. As part of this matrix, several series of tests were identified for the granulation process. This summary provides the data and results from the granulation testing. The results of the granulation matrix testing were used to identify the baseline process for testing in the PuCTF with cold surrogates in B241 at LLNL.

  14. Arginine-rich cationic proteins of human eosinophil granules

    Energy Technology Data Exchange (ETDEWEB)

    Olsson, I.; Venge, P.; Spitznagel, J.K.; Lehrer, R.I.

    1977-01-01

    Several arginine-rich cationic proteins previously isolated from granules of leukemic myeloid cells have been found to reside primarily in human eosinophil leukocytes. The major component has a molecular weight of 21,000 and it contains approximately 2.6 moles of zinc per mole of protein. Velocity centrifugation of cytoplasm from leukocytes of patients with marked eosinophilia showed that this group of proteins is packaged in the crystalloid-containing large eosinophil granules. Approximately 30% of the protein content of eosinophil granules belonged to this group of cationic proteins. Bactericidal or esterolytic activities of the cationic proteins were not detected, nor did they inhibit guinea pig anaphylatoxin or histamine-induced contraction. The basic protein previously demonstrated in guinea pig eosinophils may be analogous to the group of basic proteins of human eosinophils but great differences are found for molecular weight and amino acid composition.

  15. Studies on preparation of aceclofenac pellets by centrifugal granulator

    Directory of Open Access Journals (Sweden)

    Zibin GAO

    Full Text Available To prepare aceclofenac pellets by centrifugal granulation. Using 90~100 g of starch pellets as the core pellets,100 g of aceclofenac mixed with 50 g of microcrystalline cellulose(MCC and 4 g talc, methyl cellulose (HPMC as binder,the aceclofenac pellets were prepared by centrifugal granulation .And evaluate the quality of the pellets. The aceclofenac pellets had high yield and less losses,the pellets had a partical size of 0.70~0.88 mm(18~24 mesh)and had uniform particle size .the moisture ,drug content and dissolution meet the requirement . Aceclofenac pellets were prepared by the process of centrifugal granulation .The preparation prescription and process parameters were optimized by single factor method .and the pellets meet the standard requirements.

  16. Enterovirus Control of Translation and RNA Granule Stress Responses

    Directory of Open Access Journals (Sweden)

    Richard E. Lloyd

    2016-03-01

    Full Text Available Enteroviruses such as poliovirus (PV and coxsackievirus B3 (CVB3 have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs and processing bodies (P-bodies, PBs, which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.

  17. Enterovirus Control of Translation and RNA Granule Stress Responses

    Science.gov (United States)

    Lloyd, Richard E.

    2016-01-01

    Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation. PMID:27043612

  18. Paronychia and granulation tissue formation during treatment with isotretinoin*

    Science.gov (United States)

    Figueiras, Daniela de Almeida; Ramos, Ticiana Batista; Marinho, Ayana Karla de Oliveira Ferreira; Bezerra, Milena Soneley Mendonça; Cauas, Renata Cavalcanti

    2016-01-01

    This paper describes the association of two unusual side effects of treatment with isotretinoin for severe acne: paronychia and excess granulation tissue in the nails furrows. We report a case of male patient aged 19 years, who in the course of the 36th week of treatment with isotretinoin for acne grade III showed erythema, edema, excess granulation tissue and onychocryptosis in various nail beds of hands and feet, with no history of trauma associated. A literature review revealed few reports of these adverse events, and two clinical patterns of exuberant granulation tissue has been described: one in periungual location and other in lesions of previous acne. The rarity and lack of knowledge on the best treatment for granuloma-like reactions make this theme a considerable challenge. PMID:27192525

  19. Cystatin F Ensures Eosinophil Survival by Regulating Granule Biogenesis.

    Science.gov (United States)

    Matthews, Stephen P; McMillan, Sarah J; Colbert, Jeff D; Lawrence, Rachel A; Watts, Colin

    2016-04-19

    Eosinophils are now recognized as multifunctional leukocytes that provide critical homeostatic signals to maintain other immune cells and aid tissue repair. Paradoxically, eosinophils also express an armory of granule-localized toxins and hydrolases believed to contribute to pathology in inflammatory disease. How eosinophils deliver their supporting functions while avoiding self-inflicted injury is poorly understood. We have demonstrated that cystatin F (CF) is a critical survival factor for eosinophils. Eosinophils from CF null mice had reduced lifespan, reduced granularity, and disturbed granule morphology. In vitro, cysteine protease inhibitors restored granularity, demonstrating that control of cysteine protease activity by CF is critical for normal eosinophil development. CF null mice showed reduced pulmonary pathology in a model of allergic lung inflammation but also reduced ability to combat infection by the nematode Brugia malayi. These data identify CF as a "cytoprotectant" that promotes eosinophil survival and function by ensuring granule integrity. VIDEO ABSTRACT.

  20. Formulation and in vitro evaluation of ketoprofen fast-dissolving tablets.

    Science.gov (United States)

    Comoglu, Tansel; Inal, Ozge; Yaacoub, Hajar Ben

    2016-12-01

    Drugs exhibiting satisfactory absorption from the oral mucosa or intended for immediate pharmacological action can be advantageously formulated as orally fast-disintegrating tablets (FDTs or ODTs). Therefore, taste masking of active ingredients becomes essential in these systems because the drug is entirely released in the mouth. Despite advances in the FDT technologies, formulation of drugs with a bitter taste is still a challenge, especially when the amount of drug is high. In this study, a new solution is being developed to incorporate higher doses of a model bitter taste drug; ketoprofen, without affecting the fast-disintegrating properties of the formulation. The unpleasant taste of the active drug usually masked by adding flavoring ingredients and sweeteners to improve taste and palatability but in this study a novel approach of using a polymer; Eudragit EPO and a granulation procedure of this polymer with the active drug was applied to mask the bitter taste of ketoprofen. In order to produce ketoprofen FDT formulations, a two-stepped procedure was followed; granulation process with the taste-masking agent (Eudragit EPO) and then direct compression (F3 and F4). In F1 and F2 formulations, granulation process was not implemented in order to observe the effect of application method of Eudragit EPO. As well as observing the effect of taste-masking agent, crospovidone and sodium starch glycolate were used in different concentrations (2, 4 and 8wt%) to examine the influence of superdisintegrants on FDT properties. All the FDTs containing 30 mg ketoprofen (F1, F2, F3 and F4) were evaluated by means of in vitro quality control tests.

  1. Application of high OLR-fed aerobic granules for the treatment of low-strength wastewater: Performance, granule morphology and microbial community

    Institute of Scientific and Technical Information of China (English)

    Jingyun Ma; Xiangchun Quan; Huai Li

    2013-01-01

    Aerobic granules,pre-cultivated at the organic loading rate (OLR) of 3.0 kg COD/(m3·day),were used to treat low-strength wastewater in two sequencing batch reactors at low OLRs of 1.2 and 0.6 kg COD/(m3·day),respectively.Reactor performance,evolution of granule morphology,structure and microbial community at low OLRs under long-term operation (130 days) were investigated.Results showed that low OLRs did not cause significant damage to granule structure as a dominant granule morphology with size over 540 μm was maintained throughout the operation.Aerobic granules at sizes of about 750 μm were finally obtained at the low OLRs.The granule reactors operated at low OLRs demonstrated effective COD and ammonia removals (above 90%),smaller granule sizes and less biomass.The contents of extracellular polymeric substances in the granules were decreased while the ratios of exopolysaccharide/exoprotein were increased (above 1.0).The granules cultivated at the low OLRs showed a smoother surface and more compact structure than the seeded granules.A significant shift in microbial community was observed but the microbial diversity remained relatively stable.Confocal Laser Scanning Microscopy observation showed that the live cells were spread throughout the whole granule,while the dead cells were mainly concentrated in the outer layer of the granule,and the proteins,polysaccharides and lipids were mainly located in the central regime of the granule.In conclusion,granules cultivated at high OLRs show potential for treating low-strength organic wastewater steadily under long-term operation.

  2. UVC-induced stress granules in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Mohamed Taha Moutaoufik

    Full Text Available Stress granules (SGs are well characterized cytoplasmic RNA bodies that form under various stress conditions. We have observed that exposure of mammalian cells in culture to low doses of UVC induces the formation of discrete cytoplasmic RNA granules that were detected by immunofluorescence staining using antibodies to RNA-binding proteins. UVC-induced cytoplasmic granules are not Processing Bodies (P-bodies and are bone fide SGs as they contain TIA-1, TIA-1/R, Caprin1, FMRP, G3BP1, PABP1, well known markers, and mRNA. Concomitant with the accumulation of the granules in the cytoplasm, cells enter a quiescent state, as they are arrested in G1 phase of the cell cycle in order to repair DNA damages induced by UVC irradiation. This blockage persists as long as the granules are present. A tight correlation between their decay and re-entry into S-phase was observed. However the kinetics of their formation, their low number per cell, their absence of fusion into larger granules, their persistence over 48 hours and their slow decay, all differ from classical SGs induced by arsenite or heat treatment. The induction of these SGs does not correlate with major translation inhibition nor with phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α. We propose that a restricted subset of mRNAs coding for proteins implicated in cell cycling are removed from the translational apparatus and are sequestered in a repressed form in SGs.

  3. Mechanism for enhanced absorption of a solid dispersion formulation of LY2300559 using the artificial stomach duodenum model.

    Science.gov (United States)

    Polster, Christopher S; Wu, Sy-Juen; Gueorguieva, Ivelina; Sperry, David C

    2015-04-06

    An artificial stomach duodenum (ASD) model has been used to demonstrate the performance difference between two formulations of LY2300559, a low-solubility acidic developmental drug. The two formulations investigated were a conventional high-shear wet granulation (HSWG) formulation and a solid dispersion formulation. A pharmacokinetic study in humans demonstrated the enhanced performance of the solid dispersion formulation relative to the HSWG formulation. The Cmax and AUC of the solid dispersion was 2.6 and 1.9 times greater, respectively, compared to the HSWG formulation. In the ASD, the solid dispersion formulation performance was characterized by three main phases: (1) rapid release in the stomach, creating a supersaturated concentration of drug, (2) precipitation in the stomach, and (3) rapid redissolution of the precipitate in the duodenum to concentration levels that are supersaturated relative to crystalline drug. A series of complementary experiments were employed to describe this performance behavior mechanistically. Imaging experiments with a pH indicating dye showed that local pH gradients from meglumine in the solid dispersion formulation were responsible for creating a high initial supersaturation concentration in the stomach. Upon dissipation of meglumine, the drug precipitated in the stomach as an amorphous solid. Because the precipitated drug is in an amorphous form, it can then rapidly redissolve as it transits to the more neutral environment of the duodenum. This unexpected sequence of physical state changes gives a mechanistic explanation for the enhanced in vivo performance of the solid dispersion formulation relative to the HSWG formulation.

  4. Inhibition of calcium oxalate monohydrate growth by citrate and the effect of the background electrolyte

    Science.gov (United States)

    Weaver, Matthew L.; Qiu, S. Roger; Hoyer, John R.; Casey, William H.; Nancollas, George H.; De Yoreo, James J.

    2007-08-01

    Pathological mineralization is a common phenomenon in broad range of plants and animals. In humans, kidney stone formation is a well-known example that afflicts approximately 10% of the population. Of the various calcium salt phases that comprise human kidney stones, the primary component is calcium oxalate monohydrate (COM). Citrate, a naturally occurring molecule in the urinary system and a common therapeutic agent for treating stone disease, is a known inhibitor of COM. Understanding the physical mechanisms of citrate inhibition requires quantification of the effects of both background electrolytes and citrate on COM step kinetics. Here we report the results of an in situ AFM study of these effects, in which we measure the effect of the electrolytes LiCl, NaCl, KCl, RbCl, and CsCl, and the dependence of step speed on citrate concentration for a range of COM supersaturations. We find that varying the background electrolyte results in significant differences in the measured step speeds and in step morphology, with KCl clearly producing the smallest impact and NaCl the largest. The kinetic coefficient for the former is nearly three times larger than for the latter, while the steps change from smooth to highly serrated when KCl is changed to NaCl. The results on the dependence of step speed on citrate concentration show that citrate produces a dead zone whose width increases with citrate concentration as well as a continual reduction in kinetic coefficient with increasing citrate level. We relate these results to a molecular-scale view of inhibition that invokes a combination of kink blocking and step pinning. Furthermore, we demonstrate that the classic step-pinning model of Cabrera and Vermilyea (C-V model) does an excellent job of predicting the effect of citrate on COM step kinetics provided the model is reformulated to more realistically account for impurity adsorption, include an expression for the Gibbs-Thomson effect that is correct for all supersaturations

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

    Science.gov (United States)

    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.

  6. Modeling of lithium granule injection in NSTX using M3D-C1

    Science.gov (United States)

    Fil, A.; Kolemen, E.; Ferraro, N.; Jardin, S.; Parks, P. B.; Lunsford, R.; Maingi, R.

    2017-05-01

    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 the 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.

  7. Olaparib tablet formulation

    DEFF Research Database (Denmark)

    Plummer, Ruth; Swaisland, Helen; Leunen, Karin

    2015-01-01

    BACKGROUND: The oral PARP inhibitor olaparib has shown efficacy in patients with BRCA-mutated cancer. This Phase I, open-label, three-part study (Parts A-C) in patients with advanced solid tumours evaluated the effect of food on the pharmacokinetics (PK) of olaparib when administered in tablet...... formulation. METHODS: PK data were obtained in Part A using a two-treatment period crossover design; single-dose olaparib 300 mg (two 150 mg tablets) was administered in two prandial states: fasted and fed. In Part B, patients received olaparib tablets (300 mg bid) for 5 days under fasting conditions; in Part...... exposure to olaparib 300 mg tablets, although in the absence of an effect on the extent of olaparib absorption....

  8. To prepare and characterize microcrystalline cellulose granules using water and isopropyl alcohol as granulating agents and determine its end-point by thermal and rheological tools.

    Science.gov (United States)

    Chaudhari, Smruti P; Dave, Rutesh H

    2015-05-01

    Microcrystalline cellulose (MCC-102) is one of the most commonly used excipient in the pharmaceutical industry. For this research purpose, authors have developed a different technique to determine the end point for MCC-102 using water and isopropyl alcohol 70% (IPA) as granulating agent. Wet and dry granules obtained were characterized for their flow properties using the powder rheometer and thermal analysis. Powder rheometer was used to measure basic flowability energy (BFE), specific energy (SE), percentage compressibility, permeability and aeration. Thermal analysis includes effusivity and differential scanning calorimetry (DSC) measurements. BFE and SE results showed water granules requires high energy as compared to IPA granules. Permeability and compressibility results suggest IPA forms more porous granules and have better compressibility as compared to water granules. Hardness data reveals interesting phenomena in which as the amount of water increases, hardness decreases and vice-versa for IPA. Optimal granules were obtained in the range of 45-55% w/w. DSC data supported the formation of optimal granules. Empirical measurements like angle of repose did not reveal any significant differences between powder flow among various granules. In this paper, with the help of thermal effusivity and powder rheology we were able to differentiate between various powder flows and determine the optimal range for granule formation.

  9. The dissolution of monosodium urate monohydrate crystals: formulation of a biocompatible buffer solution with potential use in the treatment of gouty arthropathies

    Directory of Open Access Journals (Sweden)

    Gabriella Tamasi

    2013-04-01

    Full Text Available The dissolving abilities (DAs of several aqueous media for microcrystalline monosodium\turate\tmonohydrate\t(MSU, NaC5N4O3H3·H2O have been investigated using UV spectrophotometry for quantitative analytical determinations and X-ray diffraction, scanning electron microscopy and polarized light optical microscopy to assess structural aspects. High DAs were found for a buffer labeled TMT which contains tris(hydroxymethylaminomethane (TRIS, tris(hydroxymethylaminomethane\thydrochloride (TRIS·HCl, D-mannitol (MAN and taurine (TAU and gave DA30=1298(5 mg/L for synthetic MSU after 30 min incubation at 37°C and pH 7.4, most of the dissolution taking place within the first 5-10 min. Semiempirical molecular modelling techniques (ZINDO/1 show a favorable energy balance for the formation of a TRIS-urate-TRIS adduct which might explain the high DA values. Buffers containing linear or dendrimeric polyamines gave DA values which suggest that complex formation toward sodium cations is less important. An ex vivo MSU sample was found to have a significantly lower DA value (DA30=1124(5 mg/L in TMT as well as a lower crystallinity than its synthetic counterpart, possibly related to the presence of a non-crystalline impurity such as endogenous proteins. Cytotoxicity tests based on the MTT assay were used to check the biocompatibility of the TMT buffer and showed only moderate cell mortality after 24 h contact with the buffer solution.

  10. The development of a growth regime map for a novel reverse-phase wet granulation process.

    Science.gov (United States)

    Wade, Jonathan B; Martin, Gary P; Long, David F

    2016-10-15

    The feasibility of a novel reverse-phase wet granulation process has been established and potential advantages identified. Granule growth in the reverse-phase process proceeds via a steady state growth mechanism controlled by capillary forces, whereas granule growth in the conventional process proceeds via an induction growth regime controlled by viscous forces. The resultant reverse-phase granules generally have greater mass mean diameter and lower intragranular porosity when compared to conventional granules prepared under the same liquid saturation and impeller speed conditions indicating the two processes may be operating under different growth regimes. Given the observed differences in growth mechanism and consolidation behaviour of the reverse-phase and conventional granules the applicability of the current conventional granulation regime map is unclear. The aim of the present study was therefore to construct and evaluate a growth regime map, which depicts the regime as a function of liquid saturation and Stokes deformation number, for the reverse-phase granulation process. Stokes deformation number was shown to be a good predictor of both granule mass mean diameter and intragranular porosity over a wide range of process conditions. The data presented support the hypothesis that reverse-phase granules have a greater amount of surface liquid present which can dissipate collision energy and resist granule rebound resulting in the greater granule growth observed. As a result the reverse-phase granulation process results in a greater degree of granule consolidation than that produced using the conventional granulation process. Stokes deformation number was capable of differentiating these differences in the granulation process.

  11. Hydroxypropyl methylcellulose based cephalexin extended release tablets: influence of tablet formulation, hardness and storage on in vitro release kinetics.

    Science.gov (United States)

    Saravanan, Muniyandy; Sri Nataraj, Kalakonda; Ganesh, Kettavarampalayam Swaminath

    2003-08-01

    The object of this study was to develop hydroxypropyl methylcellulose (HPMC) based cephalexin extended release tablet, which can release the drug for six hours in predetermined rate. Twenty-one batches of cephalexin tablets were prepared by changing various physical and chemical parameters, in order to get required theoretical release profile. The influences of HPMC, microcrystalline cellulose powder (MCCP), granulation technique, wetting agent and tablet hardness on cephalexin release from HPMC based extended release tablets were studied. The formulated tablets were also characterized by physical and chemical parameters. The dissolution results showed that a higher amount of HPMC in tablet composition resulted in reduced drug release. Addition of MCCP resulted in faster drug release. Tablets prepared by dry granulation was released the drug slowly than the same prepared with a wet granulation technique. Addition of wetting agent in the tablets prepared with dry granulation technique showed slower release. An increase in tablet hardness resulted in faster drug release. Tablets prepared with a wet granulation technique and having a composition of 9.3% w/w HPMC with a hardness of 10-12 kg/cm(2) gave predicted release for 6 h. The in vitro release data was well fit in to Higuchi and Korsmeyer-Peppas model. Physical and chemical parameters of all formulated tablets were within acceptable limits. One batch among formulated twenty-one batches was successful and showed required theoretical release. The effect of storage on in vitro release and physicochemical parameters of successful batch was studied and was found to be in acceptable limits.

  12. Formulation and evaluation of floating tablets of niacin for sustained release

    Directory of Open Access Journals (Sweden)

    Haripriya Puthoori

    2012-01-01

    Full Text Available Niacin or nicotinic acid (NA is used in the treatment of hyperlipidemia. NA immediate release formulation shows undesirable effects like flushing of the face and neck parts. In the present study, NA floating sustained release dosage form was developed to prolong the drug release, to retain the drug delivery system above the site of absorption for the desired period of time, and to reduce the drug release rate compared to conventional formulations in order to minimize the side effects. The preformulation parameters such as flow properties and drug-excipient compatibility studies were performed. The drug excipient compatibility studies were performed using the FTIR study and the results showed that all the polymers used in the study are compatible with the pure drug. The floating sustained release tablets of niacin were prepared by the wet granulation method and the granules were evaluated for various micromeritic properties like bulk density, tapped density, Carr′s Index, Hausner′s ratio, and angle of repose. The tablets were evaluated for post-compressional parameters like average weight, thickness, hardness, friability, swelling index, floating lag time and total floating time, and in vitro drug release studies. All the formulations showed total floating time >20 hr. The concentration of the effervescent agent and the concentration and type of polymer showed an effect on the floating behavior and drug release. The formulation containing 13% sodium bicarbonate, HPMC (33% and Eudragit RS PO (4% showed required drug release up to 20 hr.

  13. Gastroretentive Drug Delivery System of Levo-Salbutamol Sulphate: Formulation and in vitro Evaluation

    Directory of Open Access Journals (Sweden)

    Kamanashis Das

    2016-03-01

    Full Text Available In order to prepare the sustained release tablet with levo-salbutamol sulphate we have used these excipients methylcellulose, PVPK30, magnesium stearate, talc, isopropyl alcohol, microcrystalline cellulose, lactose, HPMCK100, HPMCK4M. Here our approach was for making the sustained released matrix tablet by two ways, one is to make the tablet granules floating and the second one is by retarding the release of the levo-salbutamol sulphate from the matrix. We have already discussed the relationship with delaying the gastric transit time and the active drug absorption, if the tablet granules are floating in our introduction part. Since the above mentioned excipients are floating in nature so formulations with those excipients are supposed to be floating. We also showed a list of excipients those are used in the preparation of floating tablets. Now the second observation which was the release rate, among the three different formulations (mentioned in the introduction we found different types of release. Since our objective is to prepare a sustained released tablet which will give a prolong release time, in that prospect two among the three formulations were disqualified (though we have not done the kinetic study. We observed desired effect in the formulation-2 during the preparation of experiment.

  14. On Solar Granulations, Limb Darkening, and Sunspots: Brief Insights in Remembrance of Father Angelo Secchi

    Directory of Open Access Journals (Sweden)

    Robitaille P.-M.

    2011-07-01

    Full Text Available Father Angelo Secchi used the existence of solar granulation as a central line of rea- soning when he advanced that the Sun was a gaseous body with a photosphere contain- ing incandescent particulate matter (Secchi A. Sulla Struttura della Fotosfera Solare. Bullettino Meteorologico dell’Osservatorio del Collegio Romano , 30 November 1864, v.3(11, 1–3. Secchi saw the granules as condensed matter emitting the photospheric spectrum, while the darkened intergranular lanes conveyed the presence of a gaseous solar interior. Secchi also considered the nature of sunspots and limb darkening. In the context of modern solar models, opacity arguments currently account for the emis- sive properties of the photosphere. Optical depth is thought to explain limb darkening. Both temperature variations and magnetic fields are invoked to justify the weakened emissivities of sunspots, even though the presence of static magnetic fields in materi- als is not usually associated with modified emissivity. Conversely, within the context of a liquid metallic hydrogen solar model, the appearance of granules, limb darkening, and sunspots can be elegantly understood through the varying directional emissivity of condensed matter. A single explanation is applicable to all three phenomena. Granular contrast can be directly associated with the generation of limb darkening. Depending on size, granules can be analyzed by considering Kolmogoroff’s formulations and B ́ enard convection, respectively, both of which were observed using incompressible liquids, not gases. Granules follow the 2-dimensional space filling laws of Aboav-Weiner and Lewis. Their adherence to these structural laws provides supportive evidence that the granular surface of the Sun represents elements which can only be constructed from condensed matter. A gaseous Sun cannot be confined to a 2-dimensional framework. Mesogranules, supergranules, and giant cells constitute additional entities which further

  15. Discrete element modelling of fluidised bed spray granulation

    NARCIS (Netherlands)

    Goldschmidt, M.J.V.; Weijers, G.G.C.; Boerefijn, R.; Kuipers, J.A.M.

    2003-01-01

    A novel discrete element spray granulation model capturing the key features of fluidised bed hydrodynamics, liquid¿solid contacting and agglomeration is presented. The model computes the motion of every individual particle and droplet in the system, considering the gas phase as a continuum. Microsca

  16. Discrete element modelling of fluidised bed spray granulation

    NARCIS (Netherlands)

    Goldschmidt, M.J.V.; Weijers, G.G.C.; Boerefijn, R.; Kuipers, J.A.M.

    2002-01-01

    A novel discrete element spray granulation model capturing the key features of fluidised bed hydrodynamics, liquid-solid contacting and agglomeration is presented. The model computes the motion of every individual particle and droplet in the system, considering the gas phase as a continuum. Micro sc

  17. Arachnoid granules: Dandy was Dandy, Cushing and Weed were not.

    Science.gov (United States)

    Maurizi, Charles P

    2010-08-01

    Errors can be instructive. It seems that Harvey Cushing and Louis Weed provided the medical world with a faulty theory of cerebrospinal fluid absorption. Louis Weed, working in Harvey Cushing's laboratory, initially studied the movement of substances in the cerebrospinal fluid by using low-pressure studies. Results of the low-pressure studies were considered unsatisfactory and high pressure experiments were undertaken and these had results similar to earlier work done by others in human cadavers. High pressure results demonstrating movement of fluid through the arachnoid granules were deemed correct. Because of Cushing's position of authority, the theory became accepted as fact and in time proved to be entrenched dogma. Walter Dandy demonstrated in experiments on hydrocephalus and the surgical removal of the arachnoid granule system that the fluid was produced by the choroid plexuses and not absorbed by the arachnoid granules. His work was dismissed by Weed as unreliable. Examination of the pattern of deposition of corpora amylacea on the surface of the brain provides evidence that cerebrospinal fluid does not pass through arachnoid granules but passes through the choroid fissure and is recycled through choroid plexus portals. The choroid plexus portal theory can explain the findings in the low-pressure experiments of Weed. Bias and pride seem to be the source of the faulty theory. Entrenched dogma is resistant to challenge.

  18. F-Granulation Generalized Rough Entropy and Image Analysis

    Science.gov (United States)

    Pal, Sankar K.

    2012-12-01

    Role of f-granulation in handling uncertainty in machine intelligence and its significance as a facet of natural computation are discussed. Its modeling through judicious integration of rough and fuzzy sets is explained. Several tasks like case generation, clustering, classification and segmentation are described in rough-fuzzy framework demonstrating the role of f-granulation and the resulting merits. A definition of generalized rough sets is given considering both the set and granules as crisp and/or fuzzy. Based on that new entropy measures are defined using exponential and logarithmic gain functions. The superiority of rough-fuzzy integration, in terms of performance and computation time, is illustrated for the tasks of case mining in large data sets, segmenting brain MR images, and classifying remotely sensed images as examples. Neighbourhood rough sets are capable of better dimensionality reduction. The effect of fuzzy-granules and generalizations in rough sets is demonstrated for image segmentation. The article includes some of the results published elsewhere.

  19. Mechanisms underlying the beneficial effects of Kaiyu Granule for depression

    Institute of Scientific and Technical Information of China (English)

    Xi Jin; Yidan Zhang; Qiaoying Li; Jianjun Zhao

    2013-01-01

    The proprietary Chinese medicine preparation Kaiyu Granule is made of bupleurum, nutgrass ga-lingale rhizome, szechwan lovage rhizome, turmeric root tuber, white peony alba, cape jasmine fruit, fried semen ziziphi jujubae, and prepared liquorice root. It is a common recipe for the clinical treatment of depression in China. In this study, after 21 days of unpredictable stress exposure, Wistar rats exhibited similar behavioral changes to patients with depression. Moreover, G-protein-coupled inwardly rectifying K+channel 1 mRNA and protein expression were significantly reduced in rat hippocampal CA1 and CA3 regions. However, G-protein-coupled inwardly rectifying K+channel 1 mRNA, protein expression, and rat behavior were clearly better after administration of 12, 8, or 4 g/kg of Kaiyu Granule when depression model rats underwent stress. 12 g/kg of Kaiyu Granule had the most obvious effects on the increased expression of G-protein-coupled inwardly rectifying K+channel 1 mRNA and protein in rat hippocampal CA1 and CA3 regions. These results suggested that Kaiyu Granule improved depression by affecting G-protein-coupled inwardly fying K+channel 1 expression in the rat hippocampus.

  20. Spontaneous calcium waves in granule cells in cerebellar slice cultures

    DEFF Research Database (Denmark)

    Apuschkin, Mia; Ougaard, Maria; Rekling, Jens C

    2013-01-01

    and establishment of synaptic transmission. Here, we used calcium imaging in slice cultures of the postnatal cerebellum, and observe spontaneous propagating calcium waves in NeuN-positive granule-like cells. Wave formation was blocked by TTX and the AMPA antagonist NBQX, but persisted after NMDA receptor blockade...

  1. Block-based approach to modelling of granulated fertilizers' quality

    DEFF Research Database (Denmark)

    Kohonen, J.; Reinikainen, S. P.; Høskuldsson, Agnar

    2009-01-01

    Fertilizer manufacturing is a customer-driven industry, where the quality of a product is a key factor in order to survive the competition. However, measuring the most important feature with granulated fertilizers, flowability, is tedious, time-consuming and thus expensive. Flowability can...

  2. Comparison of torque measurements and near-infrared spectroscopy in characterization of a wet granulation process

    DEFF Research Database (Denmark)

    Jørgensen, Anna Cecilia; Luukkonen, Pirjo; Rantanen, Jukka

    2004-01-01

    The purpose of this study was to compare impeller torque measurements and near-infrared (NIR) spectroscopy in the characterization of the water addition phase of a wet granulation process. Additionally, the effect of hydrate formation during granulation on the impeller torque was investigated...... to process monitoring of wet granulation, also in cases where monitoring of impeller torque is difficult to apply....

  3. A model for the spray zone in early-stage fluidized bed granulation

    NARCIS (Netherlands)

    Schaafsma, S. H.; Vonk, P.; Kossen, N. W. F.; Hoffmann, A. C.

    2006-01-01

    The formation of granules in the spray zone of a top-spray fluid-bed granulation process using a known and uniform drop-size is studied experimentally and theoretically. Experimental results indicate a multi-modal size distribution of spherically-shaped granules. A model is presented to explain this

  4. Comparison of four enhancement strategies for aerobic granulation in sequencing batch reactors.

    Science.gov (United States)

    Gao, Dawen; Liu, Lin; Liang, Hong; Wu, Wei-Min

    2011-02-15

    Aerobic granules were developed in four identical sequencing batch reactors (SBRs) with synthetic wastewater to compare different strategies for the enhancement of granulation. The SBRs were operated by (a) increasing organic loading rate in R1; (b) reducing settling time in R2; (c) extending starvation period in R3; and (d) increasing shear force in R4. The results showed that four operational strategies were able to enhance aerobic granulation successfully in SBR, but that also showed different effect on the granulation process and characteristics of mature aerobic granules. The rapidest granulation was observed by using short settling time (R2) and the granules had higher extracellular polymeric substance (EPS) than other reactors. Extended starvation period (R3) and high shear force (R4) resulted in longer granulation period and the granules with higher integrity and smaller size. Higher organic loading rate (R1) resulted in the granules with larger size and higher K value. The maximum specific COD removal rates (q(max)) of the granules in all SBRs were at a similar level (0.13-0.16 g COD/h-g VSS) but the granules in R1 and R2 had higher apparent half rate constant (K) of 18 and 16 mg/L, than those in R3 and R4 (2.8 and 3.3 mg/L).

  5. Comparison of four enhancement strategies for aerobic granulation in sequencing batch reactors

    Energy Technology Data Exchange (ETDEWEB)

    Gao Dawen, E-mail: dawengao@gmail.com [School of Forestry, Northeast Forestry University, Harbin 150040 (China); State Key Laboratory of Urban Water Resource and Environment, Harbin Institute of Technology, Harbin 150090 (China); Liu Lin; Liang Hong [School of Forestry, Northeast Forestry University, Harbin 150040 (China); Wu Weimin [Department of Civil and Environmental Engineering, Stanford University, Stanford, CA 94305-4020 (United States)

    2011-02-15

    Aerobic granules were developed in four identical sequencing batch reactors (SBRs) with synthetic wastewater to compare different strategies for the enhancement of granulation. The SBRs were operated by (a) increasing organic loading rate in R1; (b) reducing settling time in R2; (c) extending starvation period in R3; and (d) increasing shear force in R4. The results showed that four operational strategies were able to enhance aerobic granulation successfully in SBR, but that also showed different effect on the granulation process and characteristics of mature aerobic granules. The rapidest granulation was observed by using short settling time (R2) and the granules had higher extracellular polymeric substance (EPS) than other reactors. Extended starvation period (R3) and high shear force (R4) resulted in longer granulation period and the granules with higher integrity and smaller size. Higher organic loading rate (R1) resulted in the granules with larger size and higher K value. The maximum specific COD removal rates (q{sub max}) of the granules in all SBRs were at a similar level (0.13-0.16 g COD/h-g VSS) but the granules in R1 and R2 had higher apparent half rate constant (K) of 18 and 16 mg/L, than those in R3 and R4 (2.8 and 3.3 mg/L).

  6. Morphology, structure and gelatinization properties of heterogeneous starch granules from high-amylose maize.

    Science.gov (United States)

    Cai, Canhui; Zhao, Lingxiao; Huang, Jun; Chen, Yifang; Wei, Cunxu

    2014-02-15

    High-amylose cereal endosperm is rich in heterogeneous starch granules. In this paper, we investigated the morphology, structure and gelatinization properties of high-amylose maize endosperm starch. Starch had individual, aggregate and elongated heterogeneous granules. Most of individual granules were round with small size and had one central hilum. Aggregate and elongated granules consisted of many subgranules with central hila, and had irregular and rod/filamentous shapes, respectively. Iodine stained starch granules showed five types of polarization colors: blue, purple, fuchsia, dark red, and interior dark blue and exterior brown. Most of individual and aggregate granules had the color of dark red, that of elongated granules the color of interior dark blue and exterior brown. Amylose was mainly distributed in the hilum region and the circumference of starch granules. Aggregate and elongated granules had higher amylose content than individual granules. Elongated and individual granules had the highest and the lowest gelatinization resistance among high-amylose maize heterogeneous starch granules, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Spray freeze granulation of submicron alumina and its sintering behavior via spark plasma sintering

    Directory of Open Access Journals (Sweden)

    Liu Wei

    2015-01-01

    Full Text Available Spray freeze granulation is an improved method based on spray granulation, solving many limitations of spray granulation. In this work, spray freeze granulation of submicron alumina is performed to explore the possibility of industrial-scale production of dense alumina via spark plasma sintering. Powder pretreatment such as sedimentation and the selection of granules with the appropriate size are employed for the maximum use of the high qualified as-prepared granules and granule sliding, which would provide a guidance for the industrial-scale production. Debound granules were densified via SPS and the corresponding sintering behaviors such as the recorded shrinkage and shrinkage rate were discussed. The comparison of sintering behaviors between granulated and as-received powder are conducted to identify the role of spray freeze granulation in sinterability for dense alumina. The Vickers hardness (Hv and the fracture toughness (KIC of the freeze granulated body are higher than the corresponding properties of the as-received body due to the more homogenous microstructure with little agglomeration in the particle packing after freeze granulation.

  8. File list: ALL.Neu.20.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: Oth.Neu.10.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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  4. File list: DNS.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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  10. File list: Oth.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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  11. Modifying sorbents in controlled release formulations to prevent herbicides pollution.

    Science.gov (United States)

    Flores Céspedes, F; Villafranca Sánchez, M; Pérez García, S; Fernández Pérez, M

    2007-10-01

    The herbicides chloridazon and metribuzin, identified as groundwater pollutants, were incorporated in alginate-based granules to obtain controlled release properties. In this research the effect of incorporation of sorbents such as bentonite, anthracite and activated carbon in alginate basic formulation were not only studied on encapsulation efficiency but also on the release rate of herbicides which was studied using water release kinetic tests. In addition, sorption studies of herbicides with bentonite, anthracite and activated carbon were made. The kinetic experiments of chloridazon and metribuzin release in water have shown that the release rate is higher in metribuzin systems than in those prepared with chloridazon, which has lower water solubility. Besides, it can be deduced that the use of sorbents reduces the release rate of the chloridazon and metribuzin in comparison to the technical product and to the alginate formulation without sorbents. The highest decrease in release rate corresponds to the formulations prepared with activated carbon as a sorbent. The water uptake, permeability, and time taken for 50% of the active ingredient to be released into water, T(50), were calculated to compare the formulations. On the basis of a parameter of an empirical equation used to fit the herbicide release data, the release of chloridazon and metribuzin from the various formulations into water is controlled by a diffusion mechanism. Sorption capacity of the sorbents for chloridazon and metribuzin, ranging from 0.53mgkg(-1) for the metribuzin sorption on bentonite to 2.03x10(5)mgkg(-1) for the sorption of chloridazon on the activated carbon, was the most important factor modulating the herbicide release.

  12. Characterization of dicalcium phosphate dihydrate cements prepared using a novel hydroxyapatite-based formulation

    Energy Technology Data Exchange (ETDEWEB)

    Alge, Daniel L [Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47908 (United States); Cruz, Grace Santa; Chu, Tien-Min Gabriel [Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202 (United States); Goebel, W Scott, E-mail: tgchu@iupui.ed [Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN 46202 (United States)

    2009-04-15

    Dicalcium phosphate dihydrate (DCPD) cements are typically prepared using beta-tricalcium phosphate (beta-TCP) as the base component. However, hydroxyapatite (HA) is an interesting alternative because of its potential for reducing cement acidity, as well as modulating cement properties via ionic substitutions. In the present study, we have characterized DCPD cements prepared with a novel formulation based on monocalcium phosphate monohydrate (MCPM) and HA. Cements were prepared using a 4:1 MCPM:HA molar ratio. The reactivity of HA in this system was verified by showing DCPD formation using poorly crystalline HA, as well as highly crystalline HA. Evaluation of cements prepared with poorly crystalline HA revealed that setting occurs rapidly in the MCPM/HA system, and that the use of a setting regulator is necessary to maintain workability of the cement paste. Compressive testing showed that MCPM/HA cements have strengths comparable to what has previously been published for DCPD cements. However, preliminary in vitro analysis of cement degradation revealed that conversion of DCPD to HA may occur much more rapidly in the MCPM/HA system compared to cements prepared with beta-TCP. Future studies should investigate this property further, as it could have important implications for the use of HA-based DCPD cement formulations.

  13. Surface Modification of Porous Titanium Granules for Improving Bioactivity.

    Science.gov (United States)

    Karaji, Zahra Gorgin; Houshmand, Behzad; Faghihi, Shahab

    The highly porous titanium granules are currently being used as bone substitute material and for bone tissue augmentation. However, they suffer from weak bone bonding ability. The aim of this study was to create a nanostructured surface oxide layer on irregularly shaped titanium granules to improve their bioactivity. This could be achieved using optimized electrochemical anodic oxidation (anodizing) and heat treatment processes. The anodizing process was done in an ethylene glycol-based electrolyte at an optimized condition of 60 V for 3 hours. The anodized granules were subsequently annealed at 450°C for 1 hour. Scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD) were used to characterize the surface structure and morphology of the granules. The in vitro bioactivity of the samples was evaluated by immersion of specimens in simulated body fluid (SBF) for 1, 2, and 3 weeks. The human osteoblastic sarcoma cell line, MG63, was used to evaluate cell viability on the samples using dimethylthiazol-diphenyl tetrazolium bromide (MTT) assay. The results demonstrated the formation of amorphous nanostructured titanium oxide after anodizing, which transformed to crystalline anatase and rutile phases upon heat treatment. After immersion in SBF, spherical aggregates of amorphous calcium phosphate were formed on the surface of the anodized sample, which turned into crystalline hydroxyapatite on the surface of the anodized annealed sample. No cytotoxicity was detected among the samples. It is suggested that anodic oxidation followed by heat treatment could be used as an effective surface treatment procedure to improve bioactivity of titanium granules implemented for bone tissue repair and augmentation.

  14. GRANULATION AND BRIQUETTING OF SOLID PRODUCTS FROM FLUE GAS DESULFURIZATION

    Directory of Open Access Journals (Sweden)

    Jan J. Hycnar

    2015-11-01

    Full Text Available Most flue gas desulfurization products can be characterized by significant solubility in water and dusting in dry state. These characteristics can cause a considerable pollution of air, water, and soil. Among many approaches to utilization of this waste, the process of agglomeration using granulation or briquetting has proved very effective. Using desulfurization products a new material of aggregate characteristics has been acquired, and this material is resistant to water and wind erosion as well as to the conditions of transportation and storage. The paper presents the results of industrial trials granulation and briquetting of calcium desulphurization products. The granulation of a mixture of phosphogypsum used with fly ash (in the share 1:5. The resulting granules characterized by a compressive strength of 41.6 MPa, the damping resistance of 70% and 14.2% abrasion. The granulate was used for the production of cement mix. The produced concrete mortar have a longer setting and hardening time, as compared to the traditional ash and gypsum mortar, and have a higher or comparable flexural and compressive strength during hardening. Briquetting trials made of a product called synthetic gypsum or rea-gypsum both in pure form and with the addition of 5% and 10% of the limestone dust. Briquettes have a high initial strength and resistance to abrasion. The values ​​of these parameters increased after 72 hours of seasoning. It was found that higher hardiness of briquettes with rea-gypsum was obtained with the impact of atmospheric conditions and higher resistance to elution of water-soluble components in comparison to ash briquettes.

  15. Plutonium Immobilization Project Baseline Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Ebbinghaus, B.

    1999-02-01

    A key milestone for the Immobilization Project (AOP Milestone 3.2a) in Fiscal Year 1998 (FY98) is the definition of the baseline composition or formulation for the plutonium ceramic form. The baseline formulation for the plutonium ceramic product must be finalized before the repository- and plant-related process specifications can be determined. The baseline formulation that is currently specified is given in Table 1.1. In addition to the baseline formulation specification, this report provides specifications for two alternative formulations, related compositional specifications (e.g., precursor compositions and mixing recipes), and other preliminary form and process specifications that are linked to the baseline formulation. The preliminary specifications, when finalized, are not expected to vary tremendously from the preliminary values given.

  16. Effects of excipients on hydrate formation in wet masses containing theophylline

    DEFF Research Database (Denmark)

    Airaksinen, Sari; Luukkonen, Pirjo; Jørgensen, Anna

    2003-01-01

    its dissolution rate. The aim of this study was to investigate whether excipients, such as alpha-lactose monohydrate or the highly water absorbing silicified microcrystalline cellulose (SMCC) can influence the hydrate formation of theophylline. In particular, the aim was to study if SMCC offers...... protection against the formation of theophylline monohydrate relative to alpha-lactose monohydrate in wet masses after an overnight equilibration and the stability of final granules during controlled storage. In addition, the aim was to study the use of spectroscopic methods to identify hydrate formation...... in the formulations containing excipients. Off-line evaluation of materials was performed using X-ray powder diffractometry, near infrared and Raman spectroscopy. alpha-Lactose monohydrate with minimal water absorbing potential was not able to prevent but enhanced hydrate formation of theophylline. Even though SMCC...

  17. Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

    Science.gov (United States)

    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.

  18. Baseline LAW Glass Formulation Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, Albert A. [USDOE Office of River Protection, Richland, WA (United States); Mooers, Cavin [The Catholic University of America, Washington, DC (United States). Vitreous State Lab.; Bazemore, Gina [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Pegg, Ian L. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Hight, Kenneth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Lai, Shan Tao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Buechele, Andrew [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Rielley, Elizabeth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Gan, Hao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Muller, Isabelle S. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Cecil, Richard [The Catholic University of America, Washington, DC (United States). Vitreous State Lab

    2013-06-13

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements.

  19. (E-2-[(2-Butyl-4-chloro-1H-imidazol-5-ylmethylidene]-N-methylhydrazine-1-carbothioamide monohydrate

    Directory of Open Access Journals (Sweden)

    Sreenath Reddy Aabaka

    2016-09-01

    Full Text Available The title thiosemicarbazide derivative, C10H16ClN5S·H2O, crystallized as a monohydrate. The molecule has an E conformation about the azomethine C=N bond that links the methylhydrazine-1-carbothioamide moiety to the imidazole ring. The butyl chain substituent on the imdazole ring is disordered over two sets of sites, with a refined occupancy ratio of 0.509 (9:0.491 (9. In the crystal, molecules are linked by O—H...N and N—H...O hydrogen bonds involving the solvent water molecule, forming chains along the c-axis direction. The chains are linked by O—H...S and N—H...S hydrogen bonds, forming a three-dimensional framework.

  20. Crystal growth, structural and thermal studies of amino acids admixtured L-arginine phosphate monohydrate single crystals

    Science.gov (United States)

    Anandan, P.; Saravanan, T.; Parthipan, G.; Kumar, R. Mohan; Bhagavannarayana, G.; Ravi, G.; Jayavel, R.

    2011-05-01

    To study the improved characteristics of L-arginine phosphate monohydrate (LAP) crystals, amino acids mixed LAP crystals have been grown by slow cooling method. Amino acids like glycine, L-alanine, and L-valine have been selected for doping. Optical quality bulk crystals have been harvested after a typical growth period of about twenty days. The effect of amino acids in the crystal lattice and molecular vibrational frequencies of various functional groups in the crystals have been studied using X-ray powder diffraction and Fourier Transform infrared (FTIR) analyses respectively. Thermal behavior of the amino acids mixed LAP crystals have been studied from the TG and DTG analyses. High-resolution X-ray diffraction studies have been carried out to find the crystalline nature. Optical transmission studies have been carried out by UV-vis spectrophotometer. The cut off wavelength is below 240 nm for the grown crystals.

  1. Spectral, optical and mechanical studies on L-histidine hydrochloride monohydrate (LHC) single crystals grown by unidirectional growth technique

    Energy Technology Data Exchange (ETDEWEB)

    Robert, R. [Department of Physics, Government Arts College (Men), Krishnagiri (India); Justin Raj, C. [Department of Physics, Loyola College, Chennai 600 034 (India); Krishnan, S. [Department of Physics, R.M.K. Engineering College, Kavaripettai 601 206 (India); Uthrakumar, R.; Dinakaran, S. [Department of Physics, Loyola College, Chennai 600 034 (India); Jerome Das, S., E-mail: sjeromedas2004@yahoo.co [Department of Physics, Loyola College, Chennai 600 034 (India)

    2010-08-15

    Single crystals of nonlinear optical L-histidine hydrochloride monohydrate (LHC) were grown in an aqueous solution by the unidirectional crystal growth method within a period of 45 days along (1 0 1) plane. The grown crystals were subjected to single crystal X-ray diffraction analysis to confirm their orthorhombic structure having space group P2{sub 1}2{sub 1}2{sub 1}. Values of several physical parameters were determined for the grown crystal. Optical transmission studies revealed very low absorption and band gap energy was calculated for the LHC crystals. Further, some optical constant were also determined for the grown crystals. Anisotropy in Vicker's microhardness led to the assessment of fracture toughness, brittleness index and yield strength for the synthesized crystals. Nonlinear optical studies were carried out for the grown crystal and second harmonic generation (SHG) efficiency was found to be three times that of KDP crystals.

  2. RETRACTED: Crystal growth and spectroscopic characterization of Aloevera amino acid added lithium sulfate monohydrate: A non-linear optical crystal

    Science.gov (United States)

    Manimekalai, R.; Antony Joseph, A.; Ramachandra Raja, C.

    2014-03-01

    This article has been retracted: please see Elsevier Policy on Article Withdrawal. This article has been retracted at the request of authors. According to the author we have reported Aloevera Amino Acid added Lithium sulphate monohydrate [AALSMH] crystal is a new nonlinear optical crystal. From the recorded high performance liquid chromatography spectrum, by matching the retention times with the known compounds, the amino acids present in our extract are identified as homocystine, isoleucine, serine, leucine and tyrosine. From the thin layer chromatography and colorimetric estimation techniques, presence of isoleucine was identified and it was also confirmed by NMR spectrum. From the above studies, we came to conclude that AALSMH is new nonlinear optical crystal. After further investigation, lattice parameter values of AALSMH are coinciding with lithium sulphate. Therefore we have decided to withdraw our paper. Sorry for the inconvenience and time spent.

  3. Formulation of poorly water-soluble drugs via coacervation--a pilot study using febantel.

    Science.gov (United States)

    De Jaeghere, W; De Geest, B G; Van Bocxlaer, J; Remon, J P; Vervaet, C; Antunes da Fonseca, A

    2013-11-01

    In this study, febantel was dissolved under increased temperature in a nonionic surfactant Lutrol L44® and subsequently mixed into an aqueous maltodextrin solution. After 8h under static conditions, coacervation or phase separation took place. (1)H NMR spectra and HPLC analysis showed that the upper phase contained mainly all febantel, while no febantel was detected in the lower phase. Fluorescent microscopy showed that maltodextrin is distributed in the lower phase. Coacervation proved to be a promising formulation technology for certain poorly water-soluble drugs, such as febantel. The coacervate phase showed an increase in in vitro dissolution kinetics, compared to Rintal® granules. These results were confirmed in an in vivo study performed on dogs. Febantel and fenbendazole showed a significant increase in plasma concentration compared to Rintal® granules. Further studies have to be performed to transform coacervates into a solid dosage form and to prove broad applicability to other poorly soluble drugs.

  4. Formulation, Optimization and in vitro Characterization of Stavudine Gastro Retentive Floating Matrix Tablets

    Directory of Open Access Journals (Sweden)

    Mahendar Rupavath

    2016-05-01

    Full Text Available The aim of the present investigation was to develop floating matrix tablets of stavudine to achieve prolong gastric residence time, leading to an increase in drug bioavailability and patient compliance. Floating tablets were prepared by wet granulation technique, using hydroxypropyl methylcellulose (HPMC K15M as synthetic, pullulan gum as natural rate controlling polymers and optimum amounts of sodium-bicarbonate and citric acid as gas generating agents in suitable ratios to generate optimum buoyancy. Developed formulations were evaluated for weight variation, thickness, hardness, friability, drug content, in vitro drug release, floating lag time and floating buoyancy. All the formulations exhibited acceptable physical properties and the best formulation (F3 was selected based on in vitro characteristics. Further, the optimized formulation was evaluated for in vivo radiographic studies by incorporating BaSO4 as radio opaque substance. All the formulations were studied for in vitro drug release characteristics for 16 h. Optimized formulation showed controlled and prolonged drug release profiles while floating over the dissolution medium. Diffusion followed by erosion drug release mechanism was observed for the formulation, indicating that water diffusion and polymer erosion played an essential role in drug release. In vivo radiographic studies revealed that the tablets remained in the stomach for 8 ± 0.5 h in fasting human volunteers and indicated that gastric retention time was increased by the floating principle, which was considered and desirable for absorption window drugs.

  5. Structures of protonated thymine and uracil and their monohydrated gas-phase ions from ultraviolet action spectroscopy and theory.

    Science.gov (United States)

    Pedersen, Sara Øvad; Byskov, Camilla Skinnerup; Turecek, Frantisek; Brøndsted Nielsen, Steen

    2014-06-19

    The strong UV chromophores thymine (Thy) and uracil (Ura) have identical heteroaromatic rings that only differ by one methyl substituent. While their photophysics has been elucidated in detail, the effect on the excited states of base protonation and single water molecules is less explored. Here we report gas-phase absorption spectra of ThyH(+) and UraH(+) and monohydrated ions and demonstrate that the substituent is not only responsible for spectral shifts but also influences the tautomer distribution, being different for bare and monohydrated ions. Spectra interpretation is aided by calculations of geometrical structures and transition energies. The lowest free-energy tautomer (denoted 178, enol-enol form) accounts for 230-280 nm (ThyH(+)) and 225-270 nm (UraH(+)) bands. ThyH(+) hardly absorbs above 300 nm, whereas a discernible band is measured for UraH(+) (275-320 nm), ascribed to the second lowest free-energy tautomer (138, enol-keto form) comprising a few percent of the UraH(+) population at room temperature. Band widths are similar to those measured of cold ions in support of very short excited-state lifetimes. Attachment of a single water increases the abundance of 138 relative to 178, 138 now clearly present for ThyH(+). 138 resembles more the tautomer present in aqueous solution than 178 does, and 138 may indeed be a relevant transition structure. The band of ThyH(+)(178) is unchanged, that of UraH(+)(178) is nearly unchanged, and that of UraH(+)(138) blue-shifts by about 10 nm. In stark contrast to protonated adenine, more than one solvating water molecule is required to re-establish the absorption of ThyH(+) and UraH(+) in aqueous solution.

  6. Fine granules showing sustained drug release prepared by high-shear melt granulation using triglycerin full behenate and milled microcrystalline cellulose.

    Science.gov (United States)

    Aoki, Hajime; Iwao, Yasunori; Uchimoto, Takeaki; Noguchi, Shuji; Kajihara, Ryusuke; Takahashi, Kana; Ishida, Masayuki; Terada, Yasuko; Suzuki, Yoshio; Itai, Shigeru

    2015-01-30

    This study aimed to prepare fine granules with a diameter less than 200μm and sustained drug release properties by melt granulation. Triglycerin full behenate (TR-FB) was examined as a new meltable binder (MB) by comparison of its properties with those of glycerin monostearate (GM), widely used as MB. The effect of milling microcrystalline cellulose (MCC), an excipient for melt granulation, on the granule properties was also investigated. TR-FB was more stable during heating and storage than GM, and produced smaller granules with narrower particle size distribution, larger yield in the 106-200μm range, uniform roundness and better sustained drug release profile than those prepared with GM. Granules prepared with milled MCC had almost the same physicochemical properties as those produced with intact MCC. However, milled MCC produced granules with a more rigid structure and smaller void space than intact MCC. Consequently, the granules produced with milled MCC showed better sustained drug release behavior than those prepared with intact MCC. We successfully prepared fine granules with sustained drug release properties and diameter of less than 200μm using TR-FB and milled MCC. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Nitrifying and denitrifying bacteria in aerobic granules formed in sequencing batch airlift reactors

    Institute of Scientific and Technical Information of China (English)

    WANG Fang; YANG Fenglin; QI Aijiu

    2007-01-01

    The purpose of this study was to investigate nitrifying bacteria and denitrifying bacteria isolated from aerobic granules.Aerobic granules were formed in an internal-circulate sequencing batch airlift reactor(SBAR)and biodegradation of NH3 -N was analyzed in the reactor.Bacteria were isolated and determined from aerobic granules using selected media.The growth properties and morphology of bacteria colonies were observed by controlling aerobic or anaerobic conditions in the culture medium.It was found that bacteria in aerobic granules were diverse and some of them were facultative aerobes.The diversity of bacteria in aerobic granules was a premise of simultaneous nitrification and denitrification.

  8. Generalized multi-layered granulations and approximations based on neighborhood systems under incomplete information systems

    Institute of Scientific and Technical Information of China (English)

    HE Ming; FENG Bo-qin

    2005-01-01

    A generalized multi-layered granulation structure used by neighborhood systems is proposed. With granulated views, the concepts of approximations under incomplete information systems are studied, which are represented by covering of the universe. With respect to different levels of granulations, a pair of lower and upper approximations is defined and an approximation structure is investigated, which lead to a more general approximation structure. The generalized multi-layered granulation structure provides a basis of the proposed framework of granular computing. Using this framework, the interesting and useful results about information granulation and approximation reasoning can be obtained. This paper presents some useful explorations about the incomplete information systems from information views.

  9. Formulation development and evaluation of orally disintegrating tablets of doxazosin mesylate

    Directory of Open Access Journals (Sweden)

    Shilpa P Chaudhari

    2012-01-01

    Full Text Available Doxazosin mesylate has some of the ideal characteristics required for an orally disintegrating tablet. There were some challenges faced during this formulation development. The aims of the present research were to mask the bitter taste of Doxazosin mesylate and to formulate orally disintegrating tablets of taste masked drug. Taste masking was performed by coating Doxazosin Mesylate with suitable polymer Eudragit powdered E-100 using spray drying technique. The resultant microspheres were then evaluated for thermal analysis, yield, particle size, entrapment efficiency and in vitro taste masking. The tablets were formulated by mixing the taste masked microspheres with different types and concentration of super-disintegrants and granulated Mannitol was selected as diluent and compressed using direct compression method. The tablets prepared were evaluated for weight variation, thickness, hardness, friability, drug content, water content, in vitro disintegration time and in vitro drug release and compared with marketed IR tablet of Doxazosin mesylate.

  10. Evaluation of Prosopis africana Seed Gum as an Extended Release Polymer for Tablet Formulation.

    Science.gov (United States)

    Nadaf, Sameer; Nnamani, Petra; Jadhav, Namdeo

    2015-06-01

    In the present work, an attempt has been made to screen Prosopis africana seed gum (PG), anionic polymer for extended release tablet formulation. Different categories of drugs (charge basis) like diclofenac sodium (DS), chlorpheniramine maleate (CPM), and ibuprofen (IB) were compacted with PG and compared with different polymers (charge basis) like xanthan gum (XG), hydroxypropyl methyl cellulose (HPMC-K100M), and chitosan (CP). For each drug, 12 batches of tablets were prepared by wet granulation technique, and granules were evaluated for flow properties, compressibility, and compactibility by Heckel and Leuenberger analysis, swelling index, in vitro dissolution studies, etc. It has been observed that granules of all batches showed acceptable flowability. According to Heckel and Leuenberger analysis, granules of PG-containing compacts showed similar and satisfactory compressibility and compactibility compared to granules of other polymers. PG showed significant swelling (P < 0.05) compared to HPMC, and better than CP and XG. Differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared (FTIR) study showed no interaction between drugs and polymers. From all PG-containing compacts of aforesaid drugs, drug release was sustained for 12 h following anomalous transport. Especially, polyelectrolyte complex formation retarded the release of oppositely charged drug (CPM-PG). However, extended release was noted in both anionic (DS) and nonionic (IB) drugs, maybe due to swollen gel. All compacts were found to be stable for 3-month period during stability study. This concludes that swelling and release retardation of PG has close resemblance to HPMC, so it can be used as extended release polymer for all types of drugs.

  11. The effects of pre versus post workout supplementation of creatine monohydrate on body composition and strength

    Science.gov (United States)

    2013-01-01

    Background Chronic supplementation with creatine monohydrate has been shown to promote increases in total intramuscular creatine, phosphocreatine, skeletal muscle mass, lean body mass and muscle fiber size. Furthermore, there is robust evidence that muscular strength and power will also increase after supplementing with creatine. However, it is not known if the timing of creatine supplementation will affect the adaptive response to exercise. Thus, the purpose of this investigation was to determine the difference between pre versus post exercise supplementation of creatine on measures of body composition and strength. Methods Nineteen healthy recreational male bodybuilders (mean ± SD; age: 23.1 ± 2.9; height: 166.0 ± 23.2 cm; weight: 80.18 ± 10.43 kg) participated in this study. Subjects were randomly assigned to one of the following groups: PRE-SUPP or POST-SUPP workout supplementation of creatine (5 grams). The PRE-SUPP group consumed 5 grams of creatine immediately before exercise. On the other hand, the POST-SUPP group consumed 5 grams immediately after exercise. Subjects trained on average five days per week for four weeks. Subjects consumed the supplement on the two non-training days at their convenience. Subjects performed a periodized, split-routine, bodybuilding workout five days per week (Chest-shoulders-triceps; Back-biceps, Legs, etc.). Body composition (Bod Pod®) and 1-RM bench press (BP) were determined. Diet logs were collected and analyzed (one random day per week; four total days analyzed). Results 2x2 ANOVA results - There was a significant time effect for fat-free mass (FFM) (F = 19.9; p = 0.001) and BP (F = 18.9; p supplementation with creatine post workout is possibly more beneficial in comparison to pre workout supplementation with regards to FFM, FM and 1-RM BP. The mean change in the PRE-SUPP and POST-SUPP groups for body weight (BW kg), FFM (kg), FM (kg) and 1-RM bench press (kg) were as follows

  12. Saltstone Clean Cap Formulation

    Energy Technology Data Exchange (ETDEWEB)

    Langton, C

    2005-04-22

    The current operation strategy for using Saltstone Vault 4 to receive 0.2 Ci/gallon salt solution waste involves pouring a clean grout layer over the radioactive grout prior to initiating pour into another cell. This will minimize the radiating surface area and reduce the dose rate at the vault and surrounding area. The Clean Cap will be used to shield about four feet of Saltstone poured into a Z-Area vault cell prior to moving to another cell. The minimum thickness of the Clean Cap layer will be determined by the cesium concentration and resulting dose levels and it is expected to be about one foot thick based on current calculations for 0.1 Ci Saltstone that is produced in the Saltstone process by stabilization of 0.2 Ci salt solution. This report documents experiments performed to identify a formulation for the Clean Cap. Thermal transient calculations, adiabatic temperature rise measurements, pour height, time between pour calculations and shielding calculations were beyond the scope and time limitations of this study. However, data required for shielding calculations (composition and specific gravity) are provided for shielding calculations. The approach used to design a Clean Cap formulation was to produce a slurry from the reference premix (10/45/45 weight percent cement/slag/fly ash) and domestic water that resembled as closely as possible the properties of the Saltstone slurry. In addition, options were investigated that may offer advantages such as less bleed water and less heat generation. The options with less bleed water required addition of dispersants. The options with lower heat contained more fly ash and less slag. A mix containing 10/45/45 weight percent cement/slag/fly ash with a water to premix ratio of 0.60 is recommended for the Clean Cap. Although this mix may generate more than 3 volume percent standing water (bleed water), it has rheological, mixing and flow properties that are similar to previously processed Saltstone. The recommended

  13. Segmental identity and cerebellar granule cell induction in rhombomere 1

    Directory of Open Access Journals (Sweden)

    Bell Esther

    2004-06-01

    Full Text Available Abstract Background Cerebellar granule cell precursors are specifically generated within the hindbrain segment, rhombomere 1, which is bounded rostrally by the midbrain/hindbrain isthmus and caudally by the boundary of the Hoxa2 expression domain. While graded signals from the isthmus have a demonstrable patterning role within this region, the significance of segmental identity for neuronal specification within rhombomere 1 is unexplored. We examined the response of granule cell precursors to the overexpression of Hoxa2, which normally determines patterns of development specific to the hindbrain. How much does the development of the cerebellum, a midbrain/hindbrain structure, reflect its neuromeric origin as a hindbrain segment? Results We show that a Gbx2-positive, Otx2-/Hoxa2-negative territory corresponding to rhombomere 1 forms prior to an identifiable isthmic organiser. Early global overexpression of Hoxa2 at embryonic day 0 has no effect on the expression of isthmic signalling molecules or the allocation of rhombomere 1 territory, but selectively results in the loss of granule cell markers at embryonic day 6 and the depletion of cell bodies from the external granule cell layer. By comparison the trochlear nucleus and locus coeruleus form normally in ventral rhombomere 1 under these conditions. Microsurgery, coupled with electroporation, to target Hoxa2 overexpression to rhombic lip precursors, reveals a profound, autonomous respecification of migration. Rhombic lip derivatives, normally destined to occupy the external granule cell layer, violate the cerebellar boundary to form a ventrolateral nucleus in a position comparable to that occupied by rhombic lip derived neurons in rhombomere 2. Conclusions Different overexpression strategies reveal that the recognition of migration cues by granule cell precursors is dependent on their identity as rhombomere 1 derivatives. Segmental patterning cues operate autonomously within the rhombic lip

  14. Granulation of sulfur-oxidizing bacteria for autotrophic denitrification.

    Science.gov (United States)

    Yang, Weiming; Lu, Hui; Khanal, Samir K; Zhao, Qing; Meng, Liao; Chen, Guang-Hao

    2016-11-01

    Sulfur-oxidizing bacteria (SOB) was successfully employed for effective autotrophic denitrification and sludge minimization in a full-scale application of saline sewage treatment in Hong Kong. In this study, a Granular Sludge Autotrophic Denitrification (GSAD) reactor was continuously operated over 600 days for SOB granulation, and to evaluate the long-term stability of SOB granules, microbial communities and denitrification efficacy. Sludge granulation initiated within the first 40 days of start-up with an average particle size of 186.4 μm and sludge volume index (SVI5) of 40 mL/g in 5 min. The sludge granules continued to grow reaching a nearly uniform size of mean diameter 1380 ± 20 μm with SVI5 of 30 mL/g during 600 days of GSAD reactor operation at hydraulic retention time of 5 h and nitrate loading rate of 0.33 kg-N/m(3)/d. The GSAD reactor with SOB granular sludge achieved 93.7 ± 2.1% nitrogen and complete sulfide removal with low sludge yield of 0.15 g-volatile suspended solids (VSS)/g-N, and much lower nitrous oxide (N2O) emission than the heterotrophic denitrifying process. Microbial community analysis using fluorescence in situ hybridization (FISH) technique revealed that granules were enriched with SOB contributing to autotrophic denitrification. Furthermore, 16S rRNA analysis showed diverse autotrophic denitrification related genera, namely Thiobacillus (32.6%), Sulfurimonas (31.3%), and Arcobacter (0.01%), accounting for 63.9% of total operational taxonomic units at the generic level. No heterotrophic denitrification related genera were detected. The results from this study could provide useful design and operating conditions with respect to SOB sludge granulation and its subsequent application in a full-scale autotrophic denitrification in the Sulfate reduction-Autotrophic denitrification-Nitrification Integrated (SANI) process. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Investigation on side-spray fluidized bed granulation with swirling airflow.

    Science.gov (United States)

    Wong, Poh Mun; Chan, Lai Wah; Heng, Paul Wan Sia

    2013-03-01

    Top-spray fluidized bed granulation with axial fluidization airflow from the bottom of the granulator is well-established in the pharmaceutical industry. The application of swirling airflow for fluidized bed granulation was more recently introduced. This study examined the effects of various process parameters on the granules produced by side-spray fluidized bed with swirling airflow using the central composite and Box-Behnken design of experiment. Influence of the amount of binder solution, spray rate, and distance between spray nozzle and powder bed were initially studied to establish operationally viable values for these parameters. This was followed by an in-depth investigation on the effects of inlet airflow rate, atomizing air pressure and distance between spray nozzle and powder bed on granule properties. It was found that the amount of binder solution had a positive correlation with granule size and percentage of lumps but a negative correlation with size distribution and Hausner ratio of the granules. Binder solution spray rate was also found to affect the granules size. High drug content uniformity was observed in all the batches of granules produced. Both inlet airflow rate and atomizing air pressure were found to correlate negatively with granule size and percentage of lumps but correlate positively with the size distribution of the granule produced. Percentage of fines was found to be significantly affected by inlet airflow rate. Distance between spray nozzle and powder bed generally affected the percentage of lumps.

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

    Science.gov (United States)

    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.

  17. Effects of extracellular polymer substances on aerobic granulation in sequencing batch reactors

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-ping; LIU Li-li; YAO Jie; SUN Li-xin; CAI Wei-min

    2009-01-01

    The effects of extracellular polymeric substances (EPS) on aerobic granulation in sequencing batch reactors (SBR) were investigated by evaluating the EPS content, and the relationship between EPS composition and surface properties of glucose-fed aerobic granules. The results show that aerobic granular sludge contains more EPS than seed sludge, and it is about 47 mg/gMLSS. Corresponding to the changes of EPS, the surface charge of microorganisms in granules increases from -0. 732 to -0. 845 meq/gMLSS, whereas the hydrophobicry changes significantly from 48.46% to 73. 16%. It is obviously that changes of EPS in sludge alter the negative surface charge and hydrophobieity of microorganisms in granules, enhance the polymeric interaction and promote the aerobic granulation. Moreover, EPS can serve as carbon and energy reserves in granulation, thus the growth between the interior and exterior bacteria is balanced, and the integrality of granules is maintained.SEM observation of the granules exhibits that EPS in granules are ropy ; by mixing with bacteria, compact matrix structure can be formed. The distribution of EPS in granules profiles the importance of EPS storage. It can be concluded that EPS play a crucial role in aerobic granulation.

  18. Study of the iron ores mixture granulation in the sintering process. Part 1. Granulation; Estudio de la granulacion de la mezcla de minerales de hierro en el proceso de sinterizacion. I parte. Granulacion

    Energy Technology Data Exchange (ETDEWEB)

    Formoso, A.; Jimenez, J.; Moro, A.; Cores, A. [Centro Nacional de Investigaciones Metalurgicas CENIM. Madrid (Spain); Moro, A. [Universidad de Oviedo (Spain); Fernandez-Pello, G.; Muniz, M. [ACERALIA. Gijon (Spain)

    2000-07-01

    The granulation process of the ore mixture is described and the fitness for granulation of several iron ores form part of the mixture is studied. With a good granulation and sintering maximum temperature control is possible to achieve the best sintered structure forming by a hematite nucleus bonded by acicular ferrites. The industrial experience of several types of granulation is described. (Author) 33 refs.

  19. MICROMORPHOLOGICAL STUDIES OF STARCH GRANULES IN SELECTED PROCESSED INDIGENOUS FLOUR OF SOUTH WESTERN NIGERIA

    Directory of Open Access Journals (Sweden)

    Adeniyi A. JAYEOLA

    2013-06-01

    Full Text Available Starch granules of yam stem tubers, plantain fruits and cassava root tubers were studied using the light microscope and then compared. Yam and plantain, both monocotyledons, had morphologically similar granules between locations, being mostly oval in shape while the granules of cassava, a dicot, were predominantly globular but varied between locations. Differences in processing methods between locations might be responsible for the observed variation in cassava granules. There is a suggestion that starch granule morphology might follow lineages in a broad sense. The unique micromorphology of cassava starch granule could make it easily detectable when adulterated, substituted or contaminated with yam or plantain granules and this could provide a cost effective clue in forensic determination.

  20. Granular computing classification algorithms based on distance measures between granules from the view of set.

    Science.gov (United States)

    Liu, Hongbing; Liu, Chunhua; Wu, Chang-an

    2014-01-01

    Granular computing classification algorithms are proposed based on distance measures between two granules from the view of set. Firstly, granules are represented as the forms of hyperdiamond, hypersphere, hypercube, and hyperbox. Secondly, the distance measure between two granules is defined from the view of set, and the union operator between two granules is formed to obtain the granule set including the granules with different granularity. Thirdly the threshold of granularity determines the union between two granules and is used to form the granular computing classification algorithms based on distance measures (DGrC). The benchmark datasets in UCI Machine Learning Repository are used to verify the performance of DGrC, and experimental results show that DGrC improved the testing accuracies.

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

    Science.gov (United States)

    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.

  2. GRANULATION TRIALS OF WASTE THE DUST SILICON CARBIDE FOR UTILIZATION IN METALLURGY

    Directory of Open Access Journals (Sweden)

    Gabriel Borowski

    2016-09-01

    Full Text Available The article presents the results of laboratory granulation tests of dust silicon carbide and the results of research on the selection of the binder and the properties of the granules obtained. The research material was a waste of the silicon carbide powder with a high fragmentation, mixed with a cement or an organic modified starch specimen. Six tests were performed in a disc granulator with 100 cm in diameter. In each series of trial specified: the type and share of the binder, the diameter of the granules, tenderness, type of structure and mechanical properties. Good granules of silicon carbide obtained with the addition of cement binder with 4% of the mass fraction and at least 24 hours of seasoning. The binder should be added twice by powdering, first in a stirred granulator, and again after manufacture. It was found that the resulting granules may be used as a replacement of ferrosilicon in the process of steelmaking.

  3. Operator Formulation of Classical Mechanics.

    Science.gov (United States)

    Cohn, Jack

    1980-01-01

    Discusses the construction of an operator formulation of classical mechanics which is directly concerned with wave packets in configuration space and is more similar to that of convential quantum theory than other extant operator formulations of classical mechanics. (Author/HM)

  4. Formulation of supergravity without superspace

    CERN Document Server

    Ferrara, S

    1979-01-01

    Supergravity, the particle theory which unifies under a unique gauge principle the quantum-mechanical concept of spin and space-time geometry, is formulated in terms of quantities defined over Minkowski space-time. 'l'he relation between this formulation and the fonnulation which uses superspace, the space-time supplemented by spinning degrees of freedom, is also briefly discussed.

  5. Study of Viability of Phosphate Solubilizing Bacteria in Phosphate granules

    Directory of Open Access Journals (Sweden)

    hajar rajabi

    2017-06-01

    Full Text Available Introduction: sustainable development and the environment are interconnected. Sustainable agriculture is continuous utilization of a farm with respect to various aspects of environmental conditions by using fewer inputs (other than Bio-fertilizers. Phosphorus is one of the essential elements for the plants. Management of soil is possible by using biological fertilizers pillar of sustainable agriculture and providing some of the phosphorus needed by plants via bio-fertilizers. Phosphorus deficiency is extremely effective on the plant growth and productivity. The application of phosphorus fertilizers is expensive and dangerous. In addition, phosphorus in the soilmay become insoluble and will be unavailable to the plants. Studies showed that phosphate solubilizing bacteria in the soil rhizosphere are active and by root exudates solve insoluble phosphates such as tricalcium phosphate, and form absorbable P for plant. Consequently, the use of microbial fertilizers could reduce excessive use of chemical fertilizers and lead to decrease their harmful effects and protect the environment and conservation of available resources. The biological phosphate fertilizer industry uses sugar beet molasses as a binder and drying granules at high temperatures. Therefore, it is important to evaluate the durability of the bacteria in molasses at high temperature. Materials and Methods: This study was designed as completely randomized design in a factorial arrangement.10 isolates were selected and the ratios of 50%, 25%, 15% and 10% of the apatite, organic matter, sulfur and soluble granule (ratio 1: 1 and 2: 1 bacteria and molasses, respectively, for each isolate was prepared. The final product was dried at 28 and 40 °C and remained for 4 months and population counted at first day and 10, 20, 30, 60, 90 and 120 days after the preparing. The population was counted by the serial dilution technique and cultured at Sperber media. Results and Discussion:Comparing the

  6. FORMULATION AND IN VITRO EVALUATION OF ARAUCARIA BIDWILLI GUM-BASED SUSTAIN RELEASE MATRIX TABLETS OF DICLOFENAE SODIUM

    Directory of Open Access Journals (Sweden)

    J. ASHOK KUMAR, M.RAJESH, S.MYTHIESH KUMAR,T. GIRIRAJ KULKARNI, V.GOPAL

    2013-10-01

    Full Text Available A gel forming Polysaccharide gum obtained form the bark of Araucaria bidwilli was employed as a matrix sustained release tablet formulation of Diclofenac sodium (a non steroidal anti inflammatory agent. The effect of Araucaria bidwilli gum (Natural and Synthetic polymer Hydroxypropyl methyl cellulose (HPMC K4 M on the release of Diclofenac sodium was studied. The FT-IR spectroscopic studies of drug, gum and mixture indicated no chemical interaction. Six formulations were prepared by wet granulation method containing Araucaria bidwilli gum powder concentration 10% 20% & 30% w\\w and 10% 20% &30% w\\w of HPMC K4 M with sufficient volume of granulating agent Polyvinyl pyrrolene (PVP K 30, Avicel pH101 as diluents, Magnesium stearate and Aerosil is used lubricant and glidant respectively.This study was carried out to find out the difference between synthetic and natural gum and whether synthetic gum can be replaced by natural gums. Physical and technological studies of granules and tablets were compliance with Pharmacopoial standards.The drug release increased with Araucaria bidwilli gum when compared to synthetics polymer concentration .The value of release exponent were found to be almost straight line and regression coefficient value between 0.938 and 0.998.This implies that the release mechanism is diffusion. Formulation F3 ( contained 30% w\\w Araucaria bidwilli gum met the desired requirements for a sustained release dosage form.

  7. Multivariate modelling of the tablet manufacturing process with wet granulation for tablet optimization and in-process control

    NARCIS (Netherlands)

    Westerhuis, J.A; Coenegracht, P.M J; Lerk, C.F

    1997-01-01

    The process of tablet manufacturing with granulation is described as a two-step process. The first step comprises wet granulation of the powder mixture, and in the second step the granules are compressed into tablets. For the modelling of the pharmaceutical process of wet granulation and tableting,

  8. Computational and structural evidence for neurotransmitter-mediated modulation of the oligomeric states of human insulin in storage granules.

    Science.gov (United States)

    Palivec, Vladimír; Viola, Cristina M; Kozak, Mateusz; Ganderton, Timothy R; Křížková, Květoslava; Turkenburg, Johan P; Halušková, Petra; Žáková, Lenka; Jiráček, Jiří; Jungwirth, Pavel; Brzozowski, Andrzej M

    2017-05-19

    Human insulin is a pivotal protein hormone controlling metabolism, growth, and aging and whose malfunctioning underlies diabetes, some cancers, and neurodegeneration. Despite its central position in human physiology, the in vivo oligomeric state and conformation of insulin in its storage granules in the pancreas are not known. In contrast, many in vitro structures of hexamers of this hormone are available and fall into three conformational states: T6, T3R(f)3, and R6 As there is strong evidence for accumulation of neurotransmitters, such as serotonin and dopamine, in insulin storage granules in pancreatic β-cells, we probed by molecular dynamics (MD) and protein crystallography (PC) if these endogenous ligands affect and stabilize insulin oligomers. Parallel studies independently converged on the observation that serotonin binds well within the insulin hexamer (site I), stabilizing it in the T3R3 conformation. Both methods indicated serotonin binding on the hexamer surface (site III) as well. MD, but not PC, indicated that dopamine was also a good site III ligand. Some of the PC studies also included arginine, which may be abundant in insulin granules upon processing of pro-insulin, and stable T3R3 hexamers loaded with both serotonin and arginine were obtained. The MD and PC results were supported further by in solution spectroscopic studies with R-state-specific chromophore. Our results indicate that the T3R3 oligomer is a plausible insulin pancreatic storage form, resulting from its complex interplay with neurotransmitters, and pro-insulin processing products. These findings may have implications for clinical insulin formulations. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. A study on the production processes of granulated iron

    Science.gov (United States)

    Nokhrina, O. I.; Rozhikhina, I. D.; Khodosov, I. E.

    2016-09-01

    The results of theoretical and experimental studies on the production process of high-quality granulated iron using hematite-magnetite iron ore and coal of different brands as a raw material are presented. According to the research the optimal coal consumption, temperature and time parameters of the metallization process, necessary for obtaining metallized materials with the specified composition and metallization degree, are defined. The conditions for the formation of metal granules with high content (over 98%) of primary iron are found. The process includes two stages: initially the solid-phase reduction of iron from oxides with production of metallized sponge material is carried out, further as the temperature increases the separation of slag and metal phases takes place.

  10. Self-organized criticality of liquefaction in saturated granules

    Institute of Scientific and Technical Information of China (English)

    吴爱祥; 孙业志; 李青松

    2003-01-01

    Utilizing the dissipative structure theory, the evolutionary process of vibrating liquefaction in saturatedgranules was analyzed. When the irreversible force increases to some degree, the system will be in a state far fromequilibrium, and the new structure probably occurs. According to synergetics, the equation of liquefaction evolutionwas deduced, and the evolutionary process was analyzed by dynamics. The evolutionary process of vibrating lique-faction is a process in which the period doubling accesses to chaos, and the fluctuation is the original driving force ofsystem evolution. The liquefaction process was also analyzed by fractal geometry. The steady process of vibratingliquefaction obeys the scaling form, and shows self-organized criticality in the course of vibration. With the incre-ment of the recurrence number, the stress of saturated granules will decrease rapidly or lose completely, and thestrain will increase rapidly, so that the granules can not sustain load and the "avalanche" phenomenon takes place.

  11. A PRELIMINARY PHARMACOGNOSTICAL AND PHYSICOCHEMICAL ASSAY OF VASAKHANDA KUSHMANDAKA GRANULES

    Directory of Open Access Journals (Sweden)

    Ghosh Kuntal

    2012-02-01

    Full Text Available Vasaka (Adhatoda vasica Nees of Acanthaceae family and Kushmanda (Benincasa hispida Thunb. of Cucurbitaceae family are the commonly used herbs in Ayurvedic system of medicine with its vivid action on various Systems. In Ayurveda, Vasaka is used in bronchial asthma, cough, diabetes mellitus and also in the pitta-kapha predominant diseases where as Kushmanda is used in Acid reflux syndrome, mental diseases, alcoholism, etc. Samsakara is a tool mentioned in Ayurveda which refers to modification or processing of drug to potentiate it, or to get desired action or to change its form. An attempt was made to change the form of Vasakhanda Kushmandaka avaleha into Vasakhanda Kushmandaka granules and assessed for its pharmacognostical and pharmaceutical characters. The present study provides the details of Vasakhanda Kushmandaka granules preparation, its pharmacognostical and physicochemical characters which may help in laying down a standard protocol for future research works.

  12. A constitutive model for sintering of granulated ceramic powders

    Science.gov (United States)

    Shinagawa, K.; Hirashima, Y.

    1998-05-01

    Sintering behavior of granulated powder is investigated to develop a constitutive model for deformation analysis of ceramic powder compacts during sintering. Spray-dried alumina is compacted by CIPing (cold isostatic pressing) and sintered at various temperatures. Shrinkage and the change in grain size of the compacts during sintering are revealed in relation to the inhomogeneous microstructure consisting of fractured and unfractured granules as a consequence of the compaction. A constitutive model for the ceramic powder compacts having the internal structure is presented; The difference in grain growth in dense and sparse regions of the compacts is taken into consideration to the model. The results calculated by the model show good agreement with that obtained by experiment.

  13. Relation between trees of fragmenting granules and supergranulation evolution

    CERN Document Server

    Roudier, Th; Rieutord, M; Frank, Z

    2016-01-01

    Context: The determination of the underlying mechanisms of the magnetic elements diffusion over the solar surface is still a challenge. Understanding the formation and evolution of the solar network (NE) is a challenge, because it provides a magnetic flux over the solar surface comparable to the flux of active regions at solar maximum. Aims: We investigate the structure and evolution of interior cells of solar supergranulation. From Hinode observations, we explore the motions on solar surface at high spatial and temporal resolution. We derive the main organization of the flows inside supergranules and their effect on the magnetic elements. Method: To probe the superganule interior cell, we used the Trees of Fragmenting Granules (TFG) evolution and their relations to horizontal Results: Evolution of TFG and their mutual interactions result in cumulative effects able to build horizontal coherent flows with longer lifetime than granulation (1 to 2 hours) over a scale up to 12\\arcsec. These flows clearly act on t...

  14. Isolating stromal stem cells from periodontal granulation tissues.

    Science.gov (United States)

    Hung, Tzu-Yuan; Lin, Hsiang-Chun; Chan, Ying-Jen; Yuan, Kuo

    2012-08-01

    Stem cell therapy is a promising area in regenerative medicine. Periodontal granulation tissues are often discarded during conventional surgery. If stromal stem cells can be isolated from these tissues, they can be used for subsequent surgery on the same patient. Fifteen human periodontal granulation tissue samples were obtained from intrabony defects during surgery. Immunohistochemistry (IHC) was carried out on five of the samples to identify STRO-1, a marker of mesenchymal stem cells. Five samples underwent flow cytometry analysis for the same marker. The remaining five samples were characterized by "colony formation unit-fibroblast" (CFU-f) assay and selected for proliferation assay, flow cytometry of stem cell markers, immunocytochemistry (ICC), multipotent differentiation assays, and repairing critical-size defects in mice. The ratio of STRO-1(+) cells detected by IHC was 5.91 ± 1.50%. The analysis of flow cytometry for STRO-1 was 6.70 ± 0.81%. Approximately two thirds of the CFU-f colonies had a strong reaction to STRO-1 in ICC staining. The cells were multipotent both in vitro and in vivo. Mice given bone grafts and stem cells showed significantly better bone healing than those without stem cells. Multipotent stromal stem cells can be isolated from human periodontal granulation tissues. These cells improve new bone formation when transplanted in mouse calvarial defects. Isolating stem cells from relatively accessible sites without extra procedures is clinically advantageous. This study demonstrated that human periodontal granulation tissues contain isolatable multipotent stem cells. The cells may be a good source for autotransplantation in subsequent treatment.

  15. Excess granulation tissue and hair loss following acitretin

    Directory of Open Access Journals (Sweden)

    Francesca Gaudiello

    2011-02-01

    Full Text Available Retinoids are routinely used in dermatology for various clinical entities including acne vulgaris, rosacea, hypertrophic scars, strie distensae, psoriasis, disorders of dyskeratinization, cancer prevention and other chronic hyperkeratotic disorders. Oral acitretin therapy is effective in the treatment of psoriasis normalizing cellular differentiation and maturation but clinical side-effects are reported. We describe the occurrence of excess granulation tissue in the nails sulcus and noncicatricial universal alopecia in a psoriatic patient receiving oral acitretin.

  16. Granule-Dependent Natural Killer Cell Cytotoxicity to Fungal Pathogens

    Science.gov (United States)

    Ogbomo, Henry; Mody, Christopher H.

    2017-01-01

    Natural killer (NK) cells kill or inhibit the growth of a number of fungi including Cryptococcus, Candida, Aspergillus, Rhizopus, and Paracoccidioides. Although many fungi are not dangerous, invasive fungal pathogens, such as Cryptococcus neoformans, cause life-threatening disease in individuals with impaired cell-mediated immunity. While there are similarities to cell-mediated killing of tumor cells, there are also important differences. Similar to tumor killing, NK cells directly kill fungi in a receptor-mediated and cytotoxic granule-dependent manner. Unlike tumor cell killing where multiple NK cell-activating receptors cooperate and signal events that mediate cytotoxicity, only the NKp30 receptor has been described to mediate signaling events that trigger the NK cell to mobilize its cytolytic payload to the site of interaction with C. neoformans and Candida albicans, subsequently leading to granule exocytosis and fungal killing. More recently, the NKp46 receptor was reported to bind Candida glabrata adhesins Epa1, 6, and 7 and directly mediate fungal clearance. A number of unanswered questions remain. For example, is only one NK cell-activating receptor sufficient for signaling leading to fungal killing? Are the signaling pathways activated by fungi similar to those activated by tumor cells during NK cell killing? How do the cytolytic granules traffic to the site of interaction with fungi, and how does this process compare with tumor killing? Recent insights into receptor use, intracellular signaling and cytolytic granule trafficking during NK cell-mediated fungal killing will be compared to tumor killing, and the implications for therapeutic approaches will be discussed. PMID:28123389

  17. A study of the piezoelectric resonance in metal organic NLO single crystals: Sodium D-isoascorbate monohydrate and Lithium L-ascorbate dihydrate

    Energy Technology Data Exchange (ETDEWEB)

    Saripalli, Ravi Kiran, E-mail: rksaripalli@physics.iisc.ernet.in; Sanath Kumar, R.; Elizabeth, Suja [Department of Physics, Indian Institute of Science, Bengaluru-560012 (India); Raghavendra Rao, K. [Department of Physics, Indian Institute of Science, Bengaluru-560012 (India); PES University, 100 Feet Ring Road,Banashankari Stage III, Banashankari, Bengaluru-560085 (India); Bhat, H. L. [Department of Physics, Indian Institute of Science, Bengaluru-560012 (India); Centre for Nano and Soft Matter Sciences, Professor UR Rao Road, Jalahalli, Bengaluru-560013 (India)

    2016-05-06

    Large single crystals of Sodium D-isoacsorbate monohydrate and Lithium L-ascorbate dehydrate were grown using solution growth technique. Dielectric constant and dielectric loss were monitored as a function of frequency at different temperatures. These are typically characterized by strong resonance peaks. The piezoelectric coefficients d{sub 31}, elastic coefficient (S{sub 11}) and electromechanical coupling coefficient (k{sub 31}) were estimated by resonance-antiresonance method. The temperature dependence of the resonance-peaks frequencies was studied.

  18. A study of the piezoelectric resonance in metal organic NLO single crystals: Sodium D-isoascorbate monohydrate and Lithium L-ascorbate dihydrate

    Science.gov (United States)

    Saripalli, Ravi Kiran; Raghavendra Rao, K.; Sanath Kumar, R.; Bhat, H. L.; Elizabeth, Suja

    2016-05-01

    Large single crystals of Sodium D-isoacsorbate monohydrate and Lithium L-ascorbate dehydrate were grown using solution growth technique. Dielectric constant and dielectric loss were monitored as a function of frequency at different temperatures. These are typically characterized by strong resonance peaks. The piezoelectric coefficients d31, elastic coefficient (S11) and electromechanical coupling coefficient (k31) were estimated by resonance-antiresonance method. The temperature dependence of the resonance-peaks frequencies was studied.

  19. Comment on the paper: "Crystal growth and spectroscopic characterization of Aloevera amino acid added lithium sulfate monohydrate: a non-linear optical crystal".

    Science.gov (United States)

    Srinivasan, Bikshandarkoil R

    2015-01-05

    The title paper (Manimekalai et al., 2014) reports a slow evaporation solution growth of a so called 'Aloevera amino acid added lithium sulfate monohydrate' (AALSMH) crystal. In this communication, many points of criticism, concerning the crystal growth, NMR spectrum and X-ray powder pattern of this so called AALSMH nonlinear optical crystal are highlighted. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Study on Thermodynamic Properties for Binary Systems of Water + L-Cysteine Hydrochloride Monohydrate, Glycerol, and D-Sorbitol at Various Temperatures

    OpenAIRE

    F. Koohyar; Rostami, A. A.; Chaichi, M. J.; F. kiani

    2013-01-01

    Viscosities, refractive indices, and densities for aqueous solution of L-cysteine hydrochloride monohydrate ([LCHCMH]) and D-sorbitol, and also densities (ρ), refractive indices ( ), excess molar volumes ( ), and change of refractive indices on mixing ( ) for aqueous solution of glycerol have been measured at several mole fractions and temperatures (between  K and  K) at atmospheric pressure. The measurements were carried out using a vibrating-tube density meter for density, an Abbe refractom...