A three step supercritical process to improve the dissolution rate of eflucimibe.

PubMed

Rodier, Elisabeth; Lochard, Hubert; Sauceau, Martial; Letourneau, Jean-Jacques; Freiss, Bernard; Fages, Jacques

2005-10-01

The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.

Formulation and performance characterization of radio-sterilized "progestin-only" microparticles intended for contraception.

PubMed

Puthli, Shivanand; Vavia, Pradeep

2009-01-01

The aim of this study was to formulate and characterize a microparticulate system of progestin-only contraceptive. Another objective was to evaluate the effect of gamma radio-sterilization on in vitro and in vivo drug release characteristics. Levonorgestrel (LNG) microspheres were fabricated using poly(lactide-co-glycolide) (PLGA) by a novel solvent evaporation technique. The formulation was optimized for drug/polymer ratio, emulsifier concentration, and process variables like speed of agitation and evaporation method. The drug to polymer ratio of 1:5 gave the optimum encapsulation efficiency. Speed of agitation influenced the spherical shape of the microparticles, lower speeds yielding less spherical particles. The speed did not have a significant influence on the drug payloads. A combination of stabilizers viz. methyl cellulose and poly vinyl alcohol with in-water solvent evaporation technique yielded microparticles without any free drug crystals on the surface. This aspect significantly eliminated the in vitro dissolution "burst effect". The residual solvent content was well within the regulatory limits. The microparticles passed the test for sterility and absence of pyrogens. In vitro dissolution conducted on the product before and after gamma radiation sterilization at 2.5 Mrad indicated no significant difference in the drug release patterns. The drug release followed zero-order kinetics in both static and agitation conditions of dissolution testing. The in vivo studies conducted in rabbits exhibited LNG release up to 1 month duration with drug levels maintained within the effective therapeutic window.

Calcite dissolution rate spectra measured by in situ digital holographic microscopy.

PubMed

Brand, Alexander S; Feng, Pan; Bullard, Jeffrey W

2017-09-01

Digital holographic microscopy in reflection mode is used to track in situ , real-time nanoscale topography evolution of cleaved (104) calcite surfaces exposed to flowing or static deionized water. The method captures full-field holograms of the surface at frame rates of up to 12.5 s -1 . Numerical reconstruction provides 3D surface topography with vertical resolution of a few nanometers and enables measurement of time-dependent local dissolution fluxes. A statistical distribution, or spectrum, of dissolution rates is generated by sampling multiple area domains on multiple crystals. The data show, as has been demonstrated by Fischer et al. (2012), that dissolution is most fully described by a rate spectrum, although the modal dissolution rate agrees well with published mean dissolution rates ( e.g. , 0.1 µmol m -2 s -1 to 0.3 µmol m -2 s -1 ). Rhombohedral etch pits and other morphological features resulting from rapid local dissolution appear at different times and are heterogeneously distributed across the surface and through the depth. This makes the distribution in rates measured on a single crystal dependent both on the sample observation field size and on time, even at nominally constant undersaturation. Statistical analysis of the inherent noise in the DHM measurements indicates that the technique is robust and that it likely can be applied to quantify and interpret rate spectra for the dissolution or growth of other minerals.

Calcite dissolution rate spectra measured by in situ digital holographic microscopy

NASA Astrophysics Data System (ADS)

Brand, Alexander S.; Feng, Pan; Bullard, Jeffrey W.

2017-09-01

Digital holographic microscopy in reflection mode is used to track in situ, real-time nanoscale topography evolution of cleaved (104) calcite surfaces exposed to flowing or static deionized water. The method captures full-field holograms of the surface at frame rates of up to 12.5 s-1. Numerical reconstruction provides 3D surface topography with vertical resolution of a few nanometers and enables measurement of time-dependent local dissolution fluxes. A statistical distribution, or spectrum, of dissolution rates is generated by sampling multiple area domains on multiple crystals. The data show, as has been demonstrated by Fischer et al. (2012), that dissolution is most fully described by a rate spectrum, although the modal dissolution rate agrees well with published mean dissolution rates (e.g., 0.1 μmol m-2 s-1 to 0.3 μmol m-2 s-1). Rhombohedral etch pits and other morphological features resulting from rapid local dissolution appear at different times and are heterogeneously distributed across the surface and through the depth. This makes the distribution in rates measured on a single crystal dependent both on the sample observation field size and on time, even at nominally constant undersaturation. Statistical analysis of the inherent noise in the DHM measurements indicates that the technique is robust and that it likely can be applied to quantify and interpret rate spectra for the dissolution or growth of other minerals.

The effect of fission-energy Xe ion irradiation on the structural integrity and dissolution of the CeO2 matrix

NASA Astrophysics Data System (ADS)

Popel, A. J.; Le Solliec, S.; Lampronti, G. I.; Day, J.; Petrov, P. K.; Farnan, I.

2017-02-01

This work considers the effect of fission fragment damage on the structural integrity and dissolution of the CeO2 matrix in water, as a simulant for the UO2 matrix of spent nuclear fuel. For this purpose, thin films of CeO2 on Si substrates were produced and irradiated by 92 MeV 129Xe23+ ions to a fluence of 4.8 × 1015 ions/cm2 to simulate fission damage that occurs within nuclear fuels along with bulk CeO2 samples. The irradiated and unirradiated samples were characterised and a static batch dissolution experiment was conducted to study the effect of the induced irradiation damage on dissolution of the CeO2 matrix. Complex restructuring took place in the irradiated films and the irradiated samples showed an increase in the amount of dissolved cerium, as compared to the corresponding unirradiated samples. Secondary phases were also observed on the surface of the irradiated CeO2 films after the dissolution experiment.

Evaluation of a biphasic in vitro dissolution test for estimating the bioavailability of carbamazepine polymorphic forms.

PubMed

Deng, Jia; Staufenbiel, Sven; Bodmeier, Roland

2017-07-15

The purpose of this study was to discriminate three crystal forms of carbamazepine (a BCS II drug) by in vitro dissolution testing and to correlate in vitro data with published in vivo data. A biphasic dissolution system (phosphate buffer pH6.8 and octanol) was used to evaluate the dissolution of the three polymorphic forms and to compare it with conventional single phase dissolution tests performed under sink and non-sink conditions. Similar dissolution profiles of three polymorphic forms were observed in the conventional dissolution test under sink conditions. Although a difference in dissolution was seen in the single phase dissolution test under non-sink conditions as well as in the aqueous phase of the biphasic test, little relevance for in vivo data was observed. In contrast, the biphasic dissolution system could discriminate between the different polymorphic forms in the octanol phase with a ranking of form III>form I>dihydrate form. This was in agreement with the in vivo performance. The dissolved drug available for oral absorption, which was dominated by dissolution and solution-mediated phase transformation, could be reflected in the biphasic dissolution test. Moreover, a good correlation was established between in vitro dissolution in the octanol phase of the biphasic test and in vivo pharmacokinetic data (R 2 =0.99). The biphasic dissolution method is a valuable tool to discriminate between different crystal forms in the formulations of poorly soluble drugs. Copyright © 2017. Published by Elsevier B.V.

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models.

PubMed

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer-Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible.

Justification of disintegration testing beyond current FDA criteria using in vitro and in silico models

PubMed Central

Uebbing, Lukas; Klumpp, Lukas; Webster, Gregory K; Löbenberg, Raimar

2017-01-01

Drug product performance testing is an important part of quality-by-design approaches, but this process often lacks the underlying mechanistic understanding of the complex interactions between the disintegration and dissolution processes involved. Whereas a recent draft guideline by the US Food and Drug Administration (FDA) has allowed the replacement of dissolution testing with disintegration testing, the mentioned criteria are not globally accepted. This study provides scientific justification for using disintegration testing rather than dissolution testing as a quality control method for certain immediate release (IR) formulations. A mechanistic approach, which is beyond the current FDA criteria, is presented. Dissolution testing via United States Pharmacopeial Convention Apparatus II at various paddle speeds was performed for immediate and extended release formulations of metronidazole. Dissolution profile fitting via DDSolver and dissolution profile predictions via DDDPlus™ were performed. The results showed that Fickian diffusion and drug particle properties (DPP) were responsible for the dissolution of the IR tablets, and that formulation factors (eg, coning) impacted dissolution only at lower rotation speeds. Dissolution was completely formulation controlled if extended release tablets were tested and DPP were not important. To demonstrate that disintegration is the most important dosage form attribute when dissolution is DPP controlled, disintegration, intrinsic dissolution and dissolution testing were performed in conventional and disintegration impacting media (DIM). Tablet disintegration was affected by DIM and model fitting to the Korsmeyer–Peppas equation showed a growing effect of the formulation in DIM. DDDPlus was able to predict tablet dissolution and the intrinsic dissolution profiles in conventional media and DIM. The study showed that disintegration has to occur before DPP-dependent dissolution can happen. The study suggests that disintegration can be used as performance test of rapidly disintegrating tablets beyond the FDA criteria. The scientific criteria and justification is that dissolution has to be DPP dependent, originated from active pharmaceutical ingredient characteristics and formulations factors have to be negligible. PMID:28442890

On the neutralization of acid rock drainage by carbonate and silicate minerals

NASA Astrophysics Data System (ADS)

Sherlock, E. J.; Lawrence, R. W.; Poulin, R.

1995-02-01

The net result of acid-generating and-neutralizing reactions within mining wastes is termed acid rock drainage (ARD). The oxidation of sulfide minerals is the major contributor to acid generation. Dissolution and alteration of various minerals can contribute to the neutralization of acid. Definitions of alkalinity, acidity, and buffer capacity are reviewed, and a detailed discussion of the dissolution and neutralizing capacity of carbonate and silicate minerals related to equilibium conditions, dissolution mechanism, and kinetics is provided. Factors that determine neutralization rate by carbonate and silicate minerals include: pH, PCO 2, equilibrium conditions, temperature, mineral composition and structure, redox conditions, and the presence of “foreign” ions. Similar factors affect sulfide oxidation. Comparison of rates shows sulfides react fastest, followed by carbonates and silicates. The differences in the reaction mechanisms and kinetics of neutralization have important implications in the prediction, control, and regulation of ARD. Current static and kinetic prediction methods upon which mine permitting, ARD control, and mine closure plans are based do not consider sample mineralogy or the kinetics of the acid-generating and-neutralizing reactions. Erroneous test interpretations and predictions can result. The importance of considering mineralogy for site-specific interpretation is highlighted. Uncertainty in prediction leads to difficulties for the mine operator in developing satisfactory and cost-effective control and remediation measures. Thus, the application of regulations and guidelines for waste management planning need to beflexible.

Developing a quality by design approach to model tablet dissolution testing: an industrial case study.

PubMed

Yekpe, Ketsia; Abatzoglou, Nicolas; Bataille, Bernard; Gosselin, Ryan; Sharkawi, Tahmer; Simard, Jean-Sébastien; Cournoyer, Antoine

2018-07-01

This study applied the concept of Quality by Design (QbD) to tablet dissolution. Its goal was to propose a quality control strategy to model dissolution testing of solid oral dose products according to International Conference on Harmonization guidelines. The methodology involved the following three steps: (1) a risk analysis to identify the material- and process-related parameters impacting the critical quality attributes of dissolution testing, (2) an experimental design to evaluate the influence of design factors (attributes and parameters selected by risk analysis) on dissolution testing, and (3) an investigation of the relationship between design factors and dissolution profiles. Results show that (a) in the case studied, the two parameters impacting dissolution kinetics are active pharmaceutical ingredient particle size distributions and tablet hardness and (b) these two parameters could be monitored with PAT tools to predict dissolution profiles. Moreover, based on the results obtained, modeling dissolution is possible. The practicality and effectiveness of the QbD approach were demonstrated through this industrial case study. Implementing such an approach systematically in industrial pharmaceutical production would reduce the need for tablet dissolution testing.

Dry powder inhalers: An overview of the in vitro dissolution methodologies and their correlation with the biopharmaceutical aspects of the drug products.

PubMed

Velaga, Sitaram P; Djuris, Jelena; Cvijic, Sandra; Rozou, Stavroula; Russo, Paola; Colombo, Gaia; Rossi, Alessandra

2018-02-15

In vitro dissolution testing is routinely used in the development of pharmaceutical products. Whilst the dissolution testing methods are well established and standardized for oral dosage forms, i.e. tablets and capsules, there are no pharmacopoeia methods or regulatory requirements for testing the dissolution of orally inhaled powders. Despite this, a wide variety of dissolution testing methods for orally inhaled powders has been developed and their bio-relevance has been evaluated. This review provides an overview of the in vitro dissolution methodologies for dry inhalation products, with particular emphasis on dry powder inhalers, where the dissolution behavior of the respirable particles can have a role on duration and absorption of the drug. Dissolution mechanisms of respirable particles as well as kinetic models have been presented. A more recent biorelevant dissolution set-ups and media for studying inhalation biopharmaceutics were also reviewed. In addition, factors affecting interplay between dissolution and absorption of deposited particles in the context of biopharmaceutical considerations of inhalation products were examined. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Newell, J; Miller, D; Stone, M

The Savannah River National Laboratory (SRNL) was tasked to provide an assessment of the downstream impacts to the Defense Waste Processing Facility (DWPF) of decisions regarding the implementation of Al-dissolution to support sludge mass reduction and processing. Based on future sludge batch compositional projections from the Liquid Waste Organization's (LWO) sludge batch plan, assessments have been made with respect to the ability to maintain comparable projected operating windows for sludges with and without Al-dissolution. As part of that previous assessment, candidate frits were identified to provide insight into melt rate for average sludge batches representing with and without Al-dissolution flowsheets.more » Initial melt rate studies using the melt rate furnace (MRF) were performed using five frits each for Cluster 2 and Cluster 4 compositions representing average without and with Al-dissolution. It was determined, however, that the REDOX endpoint (Fe{sup 2+}/{Sigma}Fe for the glass) for Clusters 2 and 4 resulted in an overly oxidized feed which negatively affected the initial melt rate tests. After the sludge was adjusted to a more reduced state, additional testing was performed with frits that contained both high and low concentrations of sodium and boron oxides. These frits were selected strictly based on the ability to ascertain compositional trends in melt rate and did not necessarily apply to any acceptability criteria for DWPF processing. The melt rate data are in general agreement with historical trends observed at SRNL and during processing of SB3 (Sludge Batch 3)and SB4 in DWPF. When MAR acceptability criteria were applied, Frit 510 was seen to have the highest melt rate at 0.67 in/hr for Cluster 2 (without Al-dissolution), which is compositionally similar to SB4. For Cluster 4 (with Al-dissolution), which is compositionally similar to SB3, Frit 418 had the highest melt rate at 0.63 in/hr. Based on this data, there appears to be a slight advantage of the Frit 510 based system without Al-dissolution relative to the Frit 418 based system with Al-dissolution. Though the without aluminum dissolution scenario suggests a slightly higher melt rate with frit 510, several points must be taken into consideration: (1) The MRF does not have the ability to assess liquid feeds and, thus, rheology impacts. Instead, the MRF is a 'static' test bed in which a mass of dried melter feed (SRAT product plus frit) is placed in an 'isothermal' furnace for a period of time to assess melt rate. These conditions, although historically effective in terms of identifying candidate frits for specific sludge batches and mapping out melt rate versus waste loading trends, do not allow for assessments of the potential impact of feed rheology on melt rate. That is, if the rheological properties of the slurried melter feed resulted in the mounding of the feed in the melter (i.e., the melter feed was thick and did not flow across the cold cap), melt rate and/or melter operations (i.e., surges) could be negatively impacted. This could affect one or both flowsheets. (2) Waste throughput factors were not determined for Frit 510 and Frit 418 over multiple waste loadings. In order to provide insight into the mission life versus canister count question, one needs to define the maximum waste throughput for both flowsheets. Due to funding limitations, the melt rate testing only evaluated melt rate at a fixed waste loading. (3) DWPF will be processing SB5 through their facility in mid-November 2008. Insight into the over arching questions of melt rate, waste throughput, and mission life can be obtained directly from the facility. It is recommended that processing of SB5 through the facility be monitored closely and that data be used as input into the decision making process on whether to implement Al-dissolution for future sludge batches.« less

Disintegration of highly soluble immediate release tablets: a surrogate for dissolution.

PubMed

Gupta, Abhay; Hunt, Robert L; Shah, Rakhi B; Sayeed, Vilayat A; Khan, Mansoor A

2009-01-01

The purpose of the work was to investigate correlation between disintegration and dissolution for immediate release tablets containing a high solubility drug and to identify formulations where disintegration test, instead of the dissolution test, may be used as the acceptance criteria based on International Conference on Harmonization Q6A guidelines. A statistical design of experiments was used to study the effect of filler, binder, disintegrating agent, and tablet hardness on the disintegration and dissolution of verapamil hydrochloride tablets. All formulation variables, i.e., filler, binder, and disintegrating agent, were found to influence tablet dissolution and disintegration, with the filler and disintegrating agent exerting the most significant influence. Slower dissolution was observed with increasing disintegration time when either the filler or the disintegrating agent was kept constant. However, no direct corelationship was observed between the disintegration and dissolution across all formulations due to the interactions between different formulation components. Although all tablets containing sodium carboxymethyl cellulose as the disintegrating agent, disintegrated in less than 3 min, half of them failed to meet the US Pharmacopeia 30 dissolution criteria for the verapamil hydrochloride tablets highlighting the dependence of dissolution process on the formulation components other than the disintegrating agent. The results identified only one formulation as suitable for using the disintegration test, instead of the dissolution test, as drug product acceptance criteria and highlight the need for systematic studies before using the disintegration test, instead of the dissolution test as the drug acceptance criteria.

Reactive solute transport in streams: A surface complexation approach for trace metal sorption

USGS Publications Warehouse

Runkel, Robert L.; Kimball, Briant A.; McKnight, Diane M.; Bencala, Kenneth E.

1999-01-01

A model for trace metals that considers in-stream transport, metal oxide precipitation-dissolution, and pH-dependent sorption is presented. Linkage between a surface complexation submodel and the stream transport equations provides a framework for modeling sorption onto static and/or dynamic surfaces. A static surface (e.g., an iron- oxide-coated streambed) is defined as a surface with a temporally constant solid concentration. Limited contact between solutes in the water column and the static surface is considered using a pseudokinetic approach. A dynamic surface (e.g., freshly precipitated metal oxides) has a temporally variable solid concentration and is in equilibrium with the water column. Transport and deposition of solute mass sorbed to the dynamic surface is represented in the stream transport equations that include precipitate settling. The model is applied to a pH-modification experiment in an acid mine drainage stream. Dissolved copper concentrations were depressed for a 3 hour period in response to the experimentally elevated pH. After passage of the pH front, copper was desorbed, and dissolved concentrations returned to ambient levels. Copper sorption is modeled by considering sorption to aged hydrous ferric oxide (HFO) on the streambed (static surface) and freshly precipitated HFO in the water column (dynamic surface). Comparison of parameter estimates with reported values suggests that naturally formed iron oxides may be more effective in removing trace metals than synthetic oxides used in laboratory studies. The model's ability to simulate pH, metal oxide precipitation-dissolution, and pH-dependent sorption provides a means of evaluating the complex interactions between trace metal chemistry and hydrologic transport at the field scale.

The differences between the branded and generic medicines using solid dosage forms: In-vitro dissolution testing

PubMed Central

Al Ameri, Mubarak Nasser; Nayuni, Nanda; Anil Kumar, K.G.; Perrett, David; Tucker, Arthur; Johnston, Atholl

2011-01-01

Introduction Dissolution is the amount of substance that goes into solution per unit time under standardised conditions of liquid/solid interface, solvent composition and temperature. Dissolution is one of the most important tools to predict the in-vivo bioavailability and in some cases to determine bioequivalence and assure interchangeability. Aim To compare the differences in dissolution behaviour of solid dosage forms between innovators (reference products) and their generic counterparts (tested products). Methods Four replicates for each batch of 37 tested medicines was carried out using A PT-DT70 dissolution tester from Pharma Test. A total of 13 branded medicines and 24 generic counterparts were obtained locally and internationally to detect any differences in their dissolution behaviour. They were tested according to the British Pharmacopeia, European Pharmacopeia and the US Pharmacopeia with the rate of dissolution determined by ultra-violet Spectrophotometery. Results Most tested medicines complied with the pharmacopoeial specifications and achieved 85% dissolution in 60 min. However, some generic medicines showed significant differences in dissolution rate at 60 and 120 min. Many generic medicines showed a slower dissolution rate than their branded counterparts such as the generic forms of omeprazole 20 mg. Some showed an incomplete dissolution such as the generic form of nifedipine 10 mg. Other generics showed faster dissolution rate than their branded counterpart such as the generic forms of meloxicam 15 mg. Moreover, some generics from different batches of the same manufacturer showed significant differences in their dissolution rate such as the generic forms of meloxicam 7.5 mg. Nevertheless, some generic medicines violated the EMA and the FDA guidelines for industry when they failed to achieve 85% dissolution at 60 min, such as the generic form of diclofenac sodium 50 mg. Conclusion Most medicines in this study complied with the pharmacopeial limits. However, some generics dissolved differently than their branded counterparts. This can clearly question the interchangeability between the branded and its generic counterpart or even among generics. PMID:25755988

Impact of vibration and agitation speed on dissolution of USP prednisone tablets RS and various IR tablet formulations.

PubMed

Seeger, Nicole; Lange, Sigrid; Klein, Sandra

2015-08-01

Dissolution testing is an in vitro procedure which is widely used in quality control (QC) of solid oral dosage forms and, given that real biorelevant test conditions are applied, can also be used as a predictive tool for the in vivo performance of such formulations. However, if a dissolution method is intended to be used for such purposes, it has to deliver results that are only determined by the quality of the test product, but not by other variables. In the recent past, more and more questions were arising on how to address the effects of vibration on dissolution test results. The present study was performed to screen for the correlation of prednisone dissolution of USP Prednisone Tablets RS with vibration caused by a commercially available vibration source as well as to investigate how drug release from a range of immediate release formulations containing class 1-4 drugs of the biopharmaceutical classification scheme is affected by vibration when performing dissolution experiments at different agitation rates. Results of the present study show that the dissolution process of oral drug formulations can be affected by vibration. However, it also becomes clear that the degree of which a certain level of vibration impacts dissolution is strongly dependent on several factors such as drug properties, formulation parameters, and the design of the dissolution method. To ensure the establishment of robust and predictive dissolution test methods, the impact of variation should thus be considered in method design and validation.

Results of Characterization and Retrieval Testing on Tank 241-C-109 Heel Solids

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

Callaway, William S.

Eight samples of heel solids from tank 241-C-109 were delivered to the 222-S Laboratory for characterization and dissolution testing. After being drained thoroughly, one-half to two-thirds of the solids were off-white to tan solids that, visually, were fairly evenly graded in size from coarse silt (30-60 μm) to medium pebbles (8-16 mm). The remaining solids were mostly strongly cemented aggregates ranging from coarse pebbles (16-32 mm) to fine cobbles (6-15 cm) in size. Solid phase characterization and chemical analysis indicated that the air-dry heel solids contained ≈58 wt% gibbsite [Al(OH){sub 3}] and ≈37 wt% natrophosphate [Na{sub 7}F(PO{sub 4}){sub 2}·19H{sub 2}O].more » The strongly cemented aggregates were mostly fine-grained gibbsite cemented with additional gibbsite. Dissolution testing was performed on two test samples. One set of tests was performed on large pieces of aggregate solids removed from the heel solids samples. The other set of dissolution tests was performed on a composite sample prepared from well-drained, air-dry heel solids that were crushed to pass a 1/4-in. sieve. The bulk density of the composite sample was 2.04 g/mL. The dissolution tests included water dissolution followed by caustic dissolution testing. In each step of the three-step water dissolution tests, a volume of water approximately equal to 3 times the initial volume of the test solids was added. In each step, the test samples were gently but thoroughly mixed for approximately 2 days at an average ambient temperature of 25 °C. The caustic dissolution tests began with the addition of sufficient 49.6 wt% NaOH to the water dissolution residues to provide ≈3.1 moles of OH for each mole of Al estimated to have been present in the starting composite sample and ≈2.6 moles of OH for each mole of Al potentially present in the starting aggregate sample. Metathesis of gibbsite to sodium aluminate was then allowed to proceed over 10 days of gentle mixing of the test samples at temperatures ranging from 26-30 °C. The metathesized sodium aluminate was then dissolved by addition of volumes of water approximately equal to 1.3 times the volumes of caustic added to the test slurries. Aluminate dissolution was allowed to proceed for 2 days at ambient temperatures of ≈29 °C. Overall, the sequential water and caustic dissolution tests dissolved and removed 80.0 wt% of the tank 241-C-109 crushed heel solids composite test sample. The 20 wt% of solids remaining after the dissolution tests were 85-88 wt% gibbsite. If the density of the residual solids was approximately equal to that of gibbsite, they represented ≈17 vol% of the initial crushed solids composite test sample. In the water dissolution tests, addition of a volume of water ≈6.9 times the initial volume of the crushed solids composite was sufficient to dissolve and recover essentially all of the natrophosphate present. The ratio of the weight of water required to dissolve the natrophosphate solids to the estimated weight of natrophosphate present was 8.51. The Environmental Simulation Program (OLI Systems, Inc., Morris Plains, New Jersey) predicts that an 8.36 w/w ratio would be required to dissolve the estimated weight of natrophosphate present in the absence of other components of the heel solids. Only minor amounts of Al-bearing solids were removed from the composite solids in the water dissolution tests. The caustic metathesis/aluminate dissolution test sequence, executed at temperatures ranging from 27-30 °C, dissolved and recovered ≈69 wt% of the gibbsite estimated to have been present in the initial crushed heel solids composite. This level of gibbsite recovery is consistent with that measured in previous scoping tests on the dissolution of gibbsite in strong caustic solutions. Overall, the sequential water and caustic dissolution tests dissolved and removed 80.3 wt% of the tank 241-C-109 aggregate solids test sample. The residual solids were 92-95 wt% gibbsite. Only a minor portion (≈4.5 wt%) of the aggregate solids was dissolved and recovered in the water dissolution test. Other than some smoothing caused by continuous mixing, the aggregates were essentially unaffected by the water dissolution tests. During the caustic metathesis/aluminate dissolution test sequence, ≈81 wt% of the gibbsite estimated to have been present in the aggregate solids was dissolved and recovered. The pieces of aggregate were significantly reduced in size but persisted as distinct pieces of solids. The increased level of gibbsite recovery, as compared to that for the crushed heel solids composite, suggests that the way the gibbsite solids and caustic solution are mixed is a key determinant of the overall efficiency of gibbsite dissolution and recovery. The liquids recovered after the caustic dissolution tests on the crushed solids composite and the aggregate solids were observed for 170 days. No precipitation of gibbsite was observed. The distribution of particle sizes in the residual solids recovered following the dissolution tests on the crushed heel solids composite was characterized. Wet sieving indicated that 21.4 wt% of the residual solids were >710 μm in size, and laser light scattering indicated that the median equivalent spherical diameter in the <710-μm solids was 35 μm. The settling behavior of the residual solids following the large-scale dissolution tests was also studied. When dispersed at a concentration of ≈1 vol% in water, ≈24 wt% of the residual solids settled at a rate >0.43 in./s; ≈68 wt% settled at rates between 0.02 and 0.43 in./s; and ≈7 wt% settled slower than 0.02 in./s.« less

In-vitro Drug Dissolution Studies in Medicinal Compounds.

PubMed

Bozal-Palabiyik, Burcin; Uslu, Bengi; Ozkan, Yalcin; Ozkan, Sibel A

2018-03-22

After oral administration, drug absorption from solid dosage forms depend on the release of the drug active compounds from the dosage form, the dissolution or solubilization of the drug under physiological conditions, and the permeability across the gastrointestinal tract. Dissolution testing is an essential part of designing more effective solid dosage forms in pharmaceutical industry. Moreover dissolution testing contributes to the selection of appropriate formulation excipients for improving the dosage form efficiency. This study aims to analyze in-vitro drug dissolution testing in solid dosage forms since 2010 in order to present a comprehensive outlook of recent trends. In doing that the previous studies in the literature are summarized in the form of a table to demonstrate the apparatuses used for dissolution testing, the media in which the solid dosage form is dissolved, the method preferred for analysis from dissolution media, the conditions of analyses and the results obtained. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Optimization of Dissolution Compartments in a Biorelevant Dissolution Apparatus Golem v2, Supported by Multivariate Analysis.

PubMed

Stupák, Ivan; Pavloková, Sylvie; Vysloužil, Jakub; Dohnal, Jiří; Čulen, Martin

2017-11-23

Biorelevant dissolution instruments represent an important tool for pharmaceutical research and development. These instruments are designed to simulate the dissolution of drug formulations in conditions most closely mimicking the gastrointestinal tract. In this work, we focused on the optimization of dissolution compartments/vessels for an updated version of the biorelevant dissolution apparatus-Golem v2. We designed eight compartments of uniform size but different inner geometry. The dissolution performance of the compartments was tested using immediate release caffeine tablets and evaluated by standard statistical methods and principal component analysis. Based on two phases of dissolution testing (using 250 and 100 mL of dissolution medium), we selected two compartment types yielding the highest measurement reproducibility. We also confirmed a statistically ssignificant effect of agitation rate and dissolution volume on the extent of drug dissolved and measurement reproducibility.

Development and validation of a discriminating in vitro dissolution method for a poorly soluble drug, olmesartan medoxomil: comparison between commercial tablets.

PubMed

Bajerski, Lisiane; Rossi, Rochele Cassanta; Dias, Carolina Lupi; Bergold, Ana Maria; Fröehlich, Pedro Eduardo

2010-06-01

A dissolution test for tablets containing 40 mg of olmesartan medoxomil (OLM) was developed and validated using both LC-UV and UV methods. After evaluation of the sink condition, dissolution medium, and stability of the drug, the method was validated using USP apparatus 2, 50 rpm rotation speed, and 900 ml of deaerated H(2)O + 0.5% sodium lauryl sulfate (w/v) at pH 6.8 (adjusted with 18% phosphoric acid) as the dissolution medium. The model-independent method using difference factor (f(1)) and similarity factor (f(2)), model-dependent method, and dissolution efficiency were employed to compare dissolution profiles. The kinetic parameters of drug release were also investigated. The obtained results provided adequate dissolution profiles. The developed dissolution test was validated according to international guidelines. Since there is no monograph for this drug in tablets, the dissolution method presented here can be used as a quality control test for OLM in this dosage form, especially in a batch to batch evaluation.

Investigating the Impact of Drug Crystallinity in Amorphous Tacrolimus Capsules on Pharmacokinetics and Bioequivalence Using Discriminatory In Vitro Dissolution Testing and Physiologically Based Pharmacokinetic Modeling and Simulation.

PubMed

Purohit, Hitesh S; Trasi, Niraj S; Sun, Dajun D; Chow, Edwin C Y; Wen, Hong; Zhang, Xinyuan; Gao, Yi; Taylor, Lynne S

2018-05-01

Delivering a drug in amorphous form in a formulated product is a strategy used to enhance the apparent solubility of a drug substance and its oral bioavailability. Drug crystallization in such products may occur during the manufacturing process or on storage, reducing the solubility advantage of the amorphous drug. However, the impact of partial drug crystallization in the drug product on the resulting bioavailability and pharmacokinetics is unknown. In this study, dissolution testing of commercial tacrolimus capsules (which are formulated to contain amorphous drug), both fresh and those containing different amounts of crystalline drug, was conducted using both United States Pharmacopeia and noncompendial dissolution tests with different dissolution media and volumes. A physiologically based pharmacokinetic (PBPK) absorption model was developed to predict the impact of crystallinity extent on the oral absorption of the products and to evaluate the discriminatory ability of the different dissolution methods. Virtual bioequivalence simulations between partially crystallized tacrolimus capsules versus fresh Prograf or generic tacrolimus capsules were performed using the PBPK model and in vitro dissolution data of the various fresh and partially crystallized capsules under United States Pharmacopeia and noncompendial dissolution conditions. The results suggest that compendial dissolution tests may not be sufficiently discriminatory with respect to the presence of crystallinity in an amorphous formulation. Nonsink dissolution tests using lower dissolution volumes generate more discriminatory profiles that predict different pharmacokinetics of tacrolimus capsules containing different extents of drug crystallinity. In conclusion, the PBPK modeling approach can be used to assess the impact of partial drug crystallinity in the formulated product and to guide the development of appropriate dissolution methods. Copyright © 2018 American Pharmacists Association®. All rights reserved.

Dissolution testing of orally disintegrating tablets.

PubMed

Kraemer, Johannes; Gajendran, Jayachandar; Guillot, Alexis; Schichtel, Julian; Tuereli, Akif

2012-07-01

For industrially manufactured pharmaceutical dosage forms, product quality tests and performance tests are required to ascertain the quality of the final product. Current compendial requirements specify a disintegration and/or a dissolution test to check the quality of oral solid dosage forms. These requirements led to a number of compendial monographs for individual products and, at times, the results obtained may not be reflective of the dosage form performance. Although a general product performance test is desirable for orally disintegrating tablets (ODTs), the complexity of the release controlling mechanisms and short time-frame of release make such tests difficult to establish. For conventional oral solid dosage forms (COSDFs), disintegration is often considered to be the prerequisite for subsequent dissolution. Hence, disintegration testing is usually insufficient to judge product performance of COSDFs. Given the very fast disintegration of ODTs, the relationship between disintegration and dissolution is worthy of closer scrutiny. This article reviews the current status of dissolution testing of ODTs to establish the product quality standards. Based on experimental results, it appears that it may be feasible to rely on the dissolution test without a need for disintegration studies for selected ODTs on the market. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

Dissolution Failure of Solid Oral Drug Products in Field Alert Reports.

PubMed

Sun, Dajun; Hu, Meng; Browning, Mark; Friedman, Rick L; Jiang, Wenlei; Zhao, Liang; Wen, Hong

2017-05-01

From 2005 to 2014, 370 data entries of dissolution failures of solid oral drug products were assessed with respect to the solubility of drug substances, dosage forms [immediate release (IR) vs. modified release (MR)], and manufacturers (brand name vs. generic). The study results show that the solubility of drug substances does not play a significant role in dissolution failures; however, MR drug products fail dissolution tests more frequently than IR drug products. When multiple variables were analyzed simultaneously, poorly water-soluble IR drug products failed the most dissolution tests, followed by poorly soluble MR drug products and very soluble MR drug products. Interestingly, the generic drug products fail dissolution tests at an earlier time point during a stability study than the brand name drug products. Whether the dissolution failure of these solid oral drug products has any in vivo implication will require further pharmacokinetic, pharmacodynamic, clinical, and drug safety evaluation. Food and Drug Administration is currently conducting risk-based assessment using in-house dissolution testing, physiologically based pharmacokinetic modeling and simulation, and post-market surveillance tools. At the meantime, this interim report will outline a general scheme of monitoring dissolution failures of solid oral dosage forms as a pharmaceutical quality indicator. Published by Elsevier Inc.

Industry's View on Using Quality Control, Biorelevant, and Clinically Relevant Dissolution Tests for Pharmaceutical Development, Registration, and Commercialization.

PubMed

Grady, Haiyan; Elder, David; Webster, Gregory K; Mao, Yun; Lin, Yiqing; Flanagan, Talia; Mann, James; Blanchard, Andy; Cohen, Michael J; Lin, Judy; Kesisoglou, Filippos; Hermans, Andre; Abend, Andreas; Zhang, Limin; Curran, David

2018-01-01

This article intends to summarize the current views of the IQ Consortium Dissolution Working Group, which comprises various industry companies, on the roles of dissolution testing throughout pharmaceutical product development, registration, commercialization, and beyond. Over the past 3 decades, dissolution testing has evolved from a routine and straightforward test as a component of end-product release into a comprehensive set of tools that the developer can deploy at various stages of the product life cycle. The definitions of commonly used dissolution approaches, how they relate to one another and how they may be applied in modern drug development, and life cycle management is described in this article. Specifically, this article discusses the purpose, advantages, and limitations of quality control, biorelevant, and clinically relevant dissolution methods. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Dissolution comparisons using a Multivariate Statistical Distance (MSD) test and a comparison of various approaches for calculating the measurements of dissolution profile comparison.

PubMed

Cardot, J-M; Roudier, B; Schütz, H

2017-07-01

The f 2 test is generally used for comparing dissolution profiles. In cases of high variability, the f 2 test is not applicable, and the Multivariate Statistical Distance (MSD) test is frequently proposed as an alternative by the FDA and EMA. The guidelines provide only general recommendations. MSD tests can be performed either on raw data with or without time as a variable or on parameters of models. In addition, data can be limited-as in the case of the f 2 test-to dissolutions of up to 85% or to all available data. In the context of the present paper, the recommended calculation included all raw dissolution data up to the first point greater than 85% as a variable-without the various times as parameters. The proposed MSD overcomes several drawbacks found in other methods.

Dissolution enhancement of tadalafil by liquisolid technique.

PubMed

Lu, Mei; Xing, Haonan; Yang, Tianzhi; Yu, Jiankun; Yang, Zhen; Sun, Yanping; Ding, Pingtian

2017-02-01

This study aimed to enhance the dissolution of tadalafil, a poorly water-soluble drug by applying liquisolid technique. The effects of two critical formulation variables, namely drug concentration (17.5% and 35%, w/w) and excipients ratio (10, 15 and 20) on dissolution rates were investigated. Pre-compression tests, including particle size distribution, flowability determination, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and scanning electron microscopy (SEM), were carried out to investigate the mechanism of dissolution enhancement. Tadalafil liquisolid tablets were prepared and their quality control tests, dissolution study, contact angle measurement, Raman mapping, and storage stability test were performed. The results suggested that all the liquisolid tablets exhibited significantly higher dissolution rates than the conventional tablets and pure tadalafil. FT-IR spectrum reflected no drug-excipient interactions. DSC and XRD studies indicated reduction in crystallinity of tadalafil, which was further confirmed by SEM and Raman mapping outcomes. The contact angle measurement demonstrated obvious increase in wetting property. Taken together, the reduction of particle size and crystallinity, and the improvement of wettability were the main mechanisms for the enhanced dissolution rate. No significant changes were observed in drug crystallinity and dissolution behavior after storage based on XRD, SEM and dissolution results.

Comprehensive validation scheme for in situ fiber optics dissolution method for pharmaceutical drug product testing.

PubMed

Mirza, Tahseen; Liu, Qian Julie; Vivilecchia, Richard; Joshi, Yatindra

2009-03-01

There has been a growing interest during the past decade in the use of fiber optics dissolution testing. Use of this novel technology is mainly confined to research and development laboratories. It has not yet emerged as a tool for end product release testing despite its ability to generate in situ results and efficiency improvement. One potential reason may be the lack of clear validation guidelines that can be applied for the assessment of suitability of fiber optics. This article describes a comprehensive validation scheme and development of a reliable, robust, reproducible and cost-effective dissolution test using fiber optics technology. The test was successfully applied for characterizing the dissolution behavior of a 40-mg immediate-release tablet dosage form that is under development at Novartis Pharmaceuticals, East Hanover, New Jersey. The method was validated for the following parameters: linearity, precision, accuracy, specificity, and robustness. In particular, robustness was evaluated in terms of probe sampling depth and probe orientation. The in situ fiber optic method was found to be comparable to the existing manual sampling dissolution method. Finally, the fiber optic dissolution test was successfully performed by different operators on different days, to further enhance the validity of the method. The results demonstrate that the fiber optics technology can be successfully validated for end product dissolution/release testing. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association

Selection of a discriminant and biorelevant in vitro dissolution test for the development of fenofibrate self-emulsifying lipid-based formulations.

PubMed

Pestieau, Aude; Krier, Fabrice; Brouwers, Adeline; Streel, Bruno; Evrard, Brigitte

2016-09-20

Fenofibrate, a BCS class II compound, has a low bioavailability especially when taken orally on an empty stomach. The challenge to find a new formulation for providing bioavailability, independent of food, is still ongoing. If the development of a suitable oral delivery formulation of BCS class II compounds is a frequent and great challenge to formulation scientists, the in vitro evaluation of these new formulations is also a great challenge. The purpose of this study was therefore to select an in vitro dissolution test that would be useful and as biorelevant as possible for the development of fenofibrate self-emulsifying lipid-based formulations. In this context, three different fenofibrate formulations, for which in vivo data are available in the literature, were tested using different dissolution tests until we found the one that was the most suitable. As part of this approach, we started with the simplest in vitro dissolution tests and progressed to tests that were increasingly more complex. The first tests were different single phase dissolution tests: a test under sink conditions based on the USP monograph, and different tests under non-sink conditions in non-biorelevant and biorelevant media. Given the inconclusive results obtained with these tests, biphasic dissolution systems were then tested: one with USP apparatus type II alone and another which combined USP apparatus types II and IV. This last combined test seemed the most suitable in vitro dissolution test for the development of the future fenofibrate lipid-based formulations we intend to develop in our own laboratory. Copyright © 2016 Elsevier B.V. All rights reserved.

Coherent anti-Stokes Raman Scattering (CARS) Microscopy Visualizes Pharmaceutical Tablets During Dissolution

PubMed Central

Fussell, Andrew L.; Kleinebudde, Peter; Herek, Jennifer; Strachan, Clare J.; Offerhaus, Herman L.

2014-01-01

Traditional pharmaceutical dissolution tests determine the amount of drug dissolved over time by measuring drug content in the dissolution medium. This method provides little direct information about what is happening on the surface of the dissolving tablet. As the tablet surface composition and structure can change during dissolution, it is essential to monitor it during dissolution testing. In this work coherent anti-Stokes Raman scattering microscopy is used to image the surface of tablets during dissolution while UV absorption spectroscopy is simultaneously providing inline analysis of dissolved drug concentration for tablets containing a 50% mixture of theophylline anhydrate and ethyl cellulose. The measurements showed that in situ CARS microscopy is capable of imaging selectively theophylline in the presence of ethyl cellulose. Additionally, the theophylline anhydrate converted to theophylline monohydrate during dissolution, with needle-shaped crystals growing on the tablet surface during dissolution. The conversion of theophylline anhydrate to monohydrate, combined with reduced exposure of the drug to the flowing dissolution medium resulted in decreased dissolution rates. Our results show that in situ CARS microscopy combined with inline UV absorption spectroscopy is capable of monitoring pharmaceutical tablet dissolution and correlating surface changes with changes in dissolution rate. PMID:25045833

Insight into the Development of Dissolution Media for BCS Class II Drugs: A Review from Quality Control and Prediction of In Vivo Performance Perspectives.

PubMed

Wu, Chunnuan; Liu, Yan; He, Zhonggui; Sun, Jin

2016-01-01

To assess in vivo behavior through in vitro method, the dissolution test is mostly used, both for quality control (QC) and for development purpose. In view of the fact that a dissolution test can hardly achieve two goals at the same time, the design of dissolution testing generally varies along with the development stage of drug products and therefore the selection of dissolution media may change with the goals of the dissolution test. To serve the QC purpose, a dissolution medium is designed to provide a sink condition; for development purpose, the dissolution medium is required to simulate the physiological conditions in the gastrointestinal tract as far as possible. In this review, we intended to provide an initial introduction to the various dissolution media applied for QC and formulation development purposes for poorly water soluble drugs. We focused on these methods like addition of cosolvents, surfactants and utilization of biphasic media, applied to provide sink conditions which are difficult to be achieved by simple aqueous buffers for lipophilic drugs, and introduced the development of physiologically relevant media for human and animals like dog and rat with respect to the choice of buffers, bile salts, lipids and so on. In addition, we further discussed the influence of biorelevant dissolution media on the modification of drug Biopharmaceutical Classification System (BCS) classification, especially for BCS class II drugs with low solubility and high permeability, the solubility of which is relatively sensitive to the presence of bile salts and lipids.

Investigation and simulation of dissolution with concurrent degradation under healthy and hypoalbuminaemic simulated parenteral conditions- case example Amphotericin B.

PubMed

Díaz de León-Ortega, Ricardo; D'Arcy, Deirdre M; Bolhuis, A; Fotaki, N

2018-06-01

Guidance on dissolution testing for parenteral formulations is limited and not often related in vivo performance. Critically ill patients represent a target cohort, frequently hypoalbuminaemic, to whom certain parenteral formulations are administered. Amphotericin B (AmB) is a poorly soluble, highly protein-bound drug, available as lipid-based formulations and used in critical illness. The aim of this study was to develop media representing hypoalbuminaemic and healthy plasma, and to understand and simulate the dissolution profile of AmB in biorelevant media. Dissolution media were prepared with bovine serum albumin (BSA) in Krebs-Ringer buffer, and tested in a flow through cell apparatus and a bottle/stirrer setup. Drug activity was tested against Candida albicans. BSA concentration was positively associated with solubility, degradation rate and maximum amount dissolved and negatively associated with dissolution rate constant and antifungal activity. In the bottle/stirrer setup, a biexponential model successfully described simultaneous dissolution and degradation and increased in agitation reduced the discriminatory ability of the test. The hydrodynamics provided by the flow-through cell apparatus was not adequate to dissolve the drug. Establishing discriminating test methods with albumin present in the dissolution media, representing the target population, supports future development of biorelevant and clinically relevant tests for parenteral formulations. Copyright © 2018 Elsevier B.V. All rights reserved.

Validation of Dissolution Testing with Biorelevant Media: An OrBiTo Study.

PubMed

Mann, James; Dressman, Jennifer; Rosenblatt, Karin; Ashworth, Lee; Muenster, Uwe; Frank, Kerstin; Hutchins, Paul; Williams, James; Klumpp, Lukas; Wielockx, Kristina; Berben, Philippe; Augustijns, Patrick; Holm, Rene; Hofmann, Michael; Patel, Sanjaykumar; Beato, Stefania; Ojala, Krista; Tomaszewska, Irena; Bruel, Jean-Luc; Butler, James

2017-12-04

Dissolution testing with biorelevant media has become widespread in the pharmaceutical industry as a means of better understanding how drugs and formulations behave in the gastrointestinal tract. Until now, however, there have been few attempts to gauge the reproducibility of results obtained with these methods. The aim of this study was to determine the interlaboratory reproducibility of biorelevant dissolution testing, using the paddle apparatus (USP 2). Thirteen industrial and three academic laboratories participated in this study. All laboratories were provided with standard protocols for running the tests: dissolution in FaSSGF to simulate release in the stomach, dissolution in a single intestinal medium, FaSSIF, to simulate release in the small intestine, and a "transfer" (two-stage) protocol to simulate the concentration profile when conditions are changed from the gastric to the intestinal environment. The test products chosen were commercially available ibuprofen tablets and zafirlukast tablets. The biorelevant dissolution tests showed a high degree of reproducibility among the participating laboratories, even though several different batches of the commercially available medium preparation powder were used. Likewise, results were almost identicalbetween the commercial biorelevant media and those produced in-house. Comparing results to previous ring studies, including those performed with USP calibrator tablets or commercially available pharmaceutical products in a single medium, the results for the biorelevant studies were highly reproducible on an interlaboratory basis. Interlaboratory reproducibility with the two-stage test was also acceptable, although the variability was somewhat greater than with the single medium tests. Biorelevant dissolution testing is highly reproducible among laboratories and can be relied upon for cross-laboratory comparisons.

Combined Experimental and Computational Approach to Predict the Glass-Water Reaction

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

Pierce, Eric M.; Bacon, Diana H.

2011-10-01

The use of mineral and glass dissolution rates measured in laboratory experiments to predict the weathering of primary minerals and volcanic and nuclear waste glasses in field studies requires the construction of rate models that accurately describe the weathering process over geologic timescales. Additionally, the need to model the long-term behavior of nuclear waste glass for the purpose of estimating radionuclide release rates requires that rate models be validated with long-term experiments. Several long-term test methods have been developed to accelerate the glass-water reaction [drip test, vapor hydration test, product consistency test B, and pressurized unsaturated flow (PUF)], thereby reducingmore » the duration required to evaluate long-term performance. Currently, the PUF test is the only method that mimics the unsaturated hydraulic properties expected in a subsurface disposal facility and simultaneously monitors the glass-water reaction. PUF tests are being conducted to accelerate the weathering of glass and validate the model parameters being used to predict long-term glass behavior. A one-dimensional reactive chemical transport simulation of glass dissolution and secondary phase formation during a 1.5-year-long PUF experiment was conducted with the Subsurface Transport Over Reactive Multiphases (STORM) code. Results show that parameterization of the computer model by combining direct bench scale laboratory measurements and thermodynamic data provides an integrated approach to predicting glass behavior over the length of the experiment. Over the 1.5-year-long test duration, the rate decreased from 0.2 to 0.01 g/(m2 day) based on B release for low-activity waste glass LAWA44. The observed decrease is approximately two orders of magnitude higher than the decrease observed under static conditions with the SON68 glass (estimated to be a decrease by four orders of magnitude) and suggests that the gel-layer properties are less protective under these dynamic conditions.« less

Combined Experimental and Computational Approach to Predict the Glass-Water Reaction

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

Pierce, Eric M; Bacon, Diana

2011-01-01

The use of mineral and glass dissolution rates measured in laboratory experiments to predict the weathering of primary minerals and volcanic and nuclear waste glasses in field studies requires the construction of rate models that accurately describe the weathering process over geologic time-scales. Additionally, the need to model the long-term behavior of nuclear waste glass for the purpose of estimating radionuclide release rates requires that rate models are validated with long-term experiments. Several long-term test methods have been developed to accelerate the glass-water reaction [drip test, vapor hydration test, product consistency test-B, and pressurized unsaturated flow (PUF)], thereby reducing themore » duration required to evaluate long-term performance. Currently, the PUF test is the only method that mimics the unsaturated hydraulic properties expected in a subsurface disposal facility and simultaneously monitors the glass-water reaction. PUF tests are being conducted to accelerate the weathering of glass and validate the model parameters being used to predict long-term glass behavior. A one-dimensional reactive chemical transport simulation of glass dissolution and secondary phase formation during a 1.5-year long PUF experiment was conducted with the subsurface transport over reactive multi-phases code. Results show that parameterization of the computer model by combining direct bench-scale laboratory measurements and thermodynamic data provides an integrated approach to predicting glass behavior over the length of the experiment. Over the 1.5-year long test duration, the rate decreased from 0.2 to 0.01 g/(m2 d) base on B release. The observed decrease is approximately two orders of magnitude higher than the decrease observed under static conditions with the SON68 glass (estimated to be a decrease by 4 orders of magnitude) and suggest the gel-layer properties are less protective under these dynamic conditions.« less

In vitro dynamic solubility test: influence of various parameters.

PubMed Central

Thélohan, S; de Meringo, A

1994-01-01

This article discusses the dissolution of mineral fibers in simulated physiological fluids (SPF), and the parameters that affect the solubility measurement in a dynamic test where an SPF runs through a cell containing fibers (Scholze and Conradt test). Solutions simulate either the extracellular fluid (pH 7.6) or the intracellular fluid (pH 4.5). The fibers have various chemical compositions and are either continuously drawn or processed as wool. The fiber solubility is determined by the amount of SiO2 (and occasionally other ions) released in the solution. Results are stated as percentage of the initial silica content released or as dissolution rate v in nm/day. The reproducibility of the test is higher with the less soluble fibers (10% solubility), than with highly soluble fibers (20% solubility). The influence of test parameters, including SPF, test duration, and surface area/volume (SA/V), has been studied. The pH and the inorganic buffer salts have a major influence: industrial glasswool composition is soluble at pH 7.6 but not at pH 4.5. The opposite is true for rock- (basalt) wool composition. For slightly soluble fibers, the dissolution rate v remains constant with time, whereas for highly soluble fibers, the dissolution rate decreases rapidly. The dissolution rates believed to occur are v1, initial dissolution rate, and v2, dissolution rate of the residual fibers. The SA of fibers varies with the mass of the fibers tested, or with the fiber diameter at equal mass. Volume, V, is the chosen flow rate. An increase in the SA/V ratio leads to a decrease in the dissolution rate.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882964

In vitro dynamic solubility test: influence of various parameters.

PubMed

Thélohan, S; de Meringo, A

1994-10-01

This article discusses the dissolution of mineral fibers in simulated physiological fluids (SPF), and the parameters that affect the solubility measurement in a dynamic test where an SPF runs through a cell containing fibers (Scholze and Conradt test). Solutions simulate either the extracellular fluid (pH 7.6) or the intracellular fluid (pH 4.5). The fibers have various chemical compositions and are either continuously drawn or processed as wool. The fiber solubility is determined by the amount of SiO2 (and occasionally other ions) released in the solution. Results are stated as percentage of the initial silica content released or as dissolution rate v in nm/day. The reproducibility of the test is higher with the less soluble fibers (10% solubility), than with highly soluble fibers (20% solubility). The influence of test parameters, including SPF, test duration, and surface area/volume (SA/V), has been studied. The pH and the inorganic buffer salts have a major influence: industrial glasswool composition is soluble at pH 7.6 but not at pH 4.5. The opposite is true for rock- (basalt) wool composition. For slightly soluble fibers, the dissolution rate v remains constant with time, whereas for highly soluble fibers, the dissolution rate decreases rapidly. The dissolution rates believed to occur are v1, initial dissolution rate, and v2, dissolution rate of the residual fibers. The SA of fibers varies with the mass of the fibers tested, or with the fiber diameter at equal mass. Volume, V, is the chosen flow rate. An increase in the SA/V ratio leads to a decrease in the dissolution rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Field-scale Prediction of Enhanced DNAPL Dissolution Using Partitioning Tracers and Flow Pattern Effects

NASA Astrophysics Data System (ADS)

Wang, F.; Annable, M. D.; Jawitz, J. W.

2012-12-01

The equilibrium streamtube model (EST) has demonstrated the ability to accurately predict dense nonaqueous phase liquid (DNAPL) dissolution in laboratory experiments and numerical simulations. Here the model is applied to predict DNAPL dissolution at a PCE-contaminated dry cleaner site, located in Jacksonville, Florida. The EST is an analytical solution with field-measurable input parameters. Here, measured data from a field-scale partitioning tracer test were used to parameterize the EST model and the predicted PCE dissolution was compared to measured data from an in-situ alcohol (ethanol) flood. In addition, a simulated partitioning tracer test from a calibrated spatially explicit multiphase flow model (UTCHEM) was also used to parameterize the EST analytical solution. The ethanol prediction based on both the field partitioning tracer test and the UTCHEM tracer test simulation closely matched the field data. The PCE EST prediction showed a peak shift to an earlier arrival time that was concluded to be caused by well screen interval differences between the field tracer test and alcohol flood. This observation was based on a modeling assessment of potential factors that may influence predictions by using UTCHEM simulations. The imposed injection and pumping flow pattern at this site for both the partitioning tracer test and alcohol flood was more complex than the natural gradient flow pattern (NGFP). Both the EST model and UTCHEM were also used to predict PCE dissolution under natural gradient conditions, with much simpler flow patterns than the forced-gradient double five spot of the alcohol flood. The NGFP predictions based on parameters determined from tracer tests conducted with complex flow patterns underestimated PCE concentrations and total mass removal. This suggests that the flow patterns influence aqueous dissolution and that the aqueous dissolution under the NGFP is more efficient than dissolution under complex flow patterns.

The use of ordered mixtures for improving the dissolution rate of low solubility compounds.

PubMed

Nyström, C; Westerberg, M

1986-03-01

The dissolution rate of micronized griseofulvin has been investigated, both for the agglomerated raw material and the material formulated as an ordered mixture, by means of the USP XX paddle method. During the experiments, which were performed at sink condition and constant temperature, the effects of adding a surfactant and of agitation were tested. The ordered mixture with sodium chloride gave a fast dissolution rate, practically independent of the test parameters. Micronized griseofulvin alone gave dissolution profiles that were improved by adding polysorbate 80 and by increased agitation, but the dissolution rates obtained were much lower than those for the ordered mixture. It was concluded that the rate limiting step in the dissolution of griseofulvin as the raw material is the penetration of the dissolution medium into the agglomerates. With an ordered mixture, these agglomerates were deaggregated during the mixing process, producing a system in which the entire external surface area of the primary particles was exposed to the dissolution medium. This conclusion was supported by calculation of the contact surface areas taking part in the dissolution process for the systems tested. The procedure developed in this study could be applied to preformulation work where a cohesive, low solubility drug of hydrophobic nature is to be formulated.

Lyophilic matrix method for dissolution and release studies of nanoscale particles.

PubMed

Pessi, Jenni; Svanbäck, Sami; Lassila, Ilkka; Hæggström, Edward; Yliruusi, Jouko

2017-10-25

We introduce a system with a lyophilic matrix to aid dissolution studies of powders and particulate systems. This lyophilic matrix method (LM method) is based on the ability to discriminate between non-dissolved particles and the dissolved species. In the LM method the test substance is embedded in a thin lyophilic core-shell matrix. This permits rapid contact with the dissolution medium while minimizing dispersion of non-dissolved particles without presenting a substantial diffusion barrier. The method produces realistic dissolution and release results for particulate systems, especially those featuring nanoscale particles. By minimizing method-induced effects on the dissolution profile of nanopowders, the LM method overcomes shortcomings associated with current dissolution tests. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative Application of PLS and PCR Methods to Simultaneous Quantitative Estimation and Simultaneous Dissolution Test of Zidovudine - Lamivudine Tablets.

PubMed

Üstündağ, Özgür; Dinç, Erdal; Özdemir, Nurten; Tilkan, M Günseli

2015-01-01

In the development strategies of new drug products and generic drug products, the simultaneous in-vitro dissolution behavior of oral dosage formulations is the most important indication for the quantitative estimation of efficiency and biopharmaceutical characteristics of drug substances. This is to force the related field's scientists to improve very powerful analytical methods to get more reliable, precise and accurate results in the quantitative analysis and dissolution testing of drug formulations. In this context, two new chemometric tools, partial least squares (PLS) and principal component regression (PCR) were improved for the simultaneous quantitative estimation and dissolution testing of zidovudine (ZID) and lamivudine (LAM) in a tablet dosage form. The results obtained in this study strongly encourage us to use them for the quality control, the routine analysis and the dissolution test of the marketing tablets containing ZID and LAM drugs.

The impact of calcium carbonate as pore forming agent and drug entrapment method towards drug dissolution mechanism of amoxicillin trihydrate encapsulated by chitosan-methyl cellulose semi-IPN hydrogel for floating drug delivery system

NASA Astrophysics Data System (ADS)

Dewantara, Fauzi; Budianto, Emil

2018-04-01

Chitosan-methyl cellulose semi-IPN hydrogel is used as floating drug delivery system, and calcium carbonate also added as pore forming agent. The hydrogel network arranged by not only using biopolymer chitosan and methyl cellulose, but also the crosslink agent that is glutaraldehyde. Amoxicillin trihydrate entrapped into the polymer network with two different method, in situ loading and post loading. Furthermore both method has been tested for drug entrapment efficiency along with drug dissolution test, and the result for drug entrapment efficiency is in situ loading method has highest value of 100%, compared to post loading method which has value only 71%. Moreover, at the final time of drug dissolution test shows in situ loading method has value of 96% for total accumulative of drug dissolution, meanwhile post loading method has 72%. The value of drug dissolution test from both method is used for analyzing drug dissolution mechanism of amoxicillin trihydrate from hydrogel network with four mathematical drug mechanism models as parameter. The polymer network encounter destructive degradation causes by acid solution which used as dissolution medium, and the level of degradation is observed with optical microscope. However the result shows that degradation of the polymer network doesn't affect drug dissolution mechanism directly. Although the pore forming agent causes the pore inside the hydrogel network create interconnection and it was quite influential to drug dissolution mechanism. Interconnected pore is observed with Scanning Electron Microscope (SEM) and shows that the amount and area of interconnected pore inside the hydrogel network is increasing as drug dissolution goes on.

Using the technique of computed tomography for nondestructive analysis of pharmaceutical dosage forms

NASA Astrophysics Data System (ADS)

de Oliveira, José Martins, Jr.; Mangini, F. Salvador; Carvalho Vila, Marta Maria Duarte; ViníciusChaud, Marco

2013-05-01

This work presents an alternative and non-conventional technique for evaluatingof physic-chemical properties of pharmaceutical dosage forms, i.e. we used computed tomography (CT) technique as a nondestructive technique to visualize internal structures of pharmaceuticals dosage forms and to conduct static and dynamical studies. The studies were conducted involving static and dynamic situations through the use of tomographic images, generated by the scanner at University of Sorocaba - Uniso. We have shown that through the use of tomographic images it is possible to conduct studies of porosity, densities, analysis of morphological parameters and performing studies of dissolution. Our results are in agreement with the literature, showing that CT is a powerful tool for use in the pharmaceutical sciences.

Errors in reporting on dissolution research: methodological and statistical implications.

PubMed

Jasińska-Stroschein, Magdalena; Kurczewska, Urszula; Orszulak-Michalak, Daria

2017-02-01

In vitro dissolution testing provides useful information at clinical and preclinical stages of the drug development process. The study includes pharmaceutical papers on dissolution research published in Polish journals between 2010 and 2015. They were analyzed with regard to information provided by authors about chosen methods, performed validation, statistical reporting or assumptions used to properly compare release profiles considering the present guideline documents addressed to dissolution methodology and its validation. Of all the papers included in the study, 23.86% presented at least one set of validation parameters, 63.64% gave the results of the weight uniformity test, 55.68% content determination, 97.73% dissolution testing conditions, and 50% discussed a comparison of release profiles. The assumptions for methods used to compare dissolution profiles were discussed in 6.82% of papers. By means of example analyses, we demonstrate that the outcome can be influenced by the violation of several assumptions or selection of an improper method to compare dissolution profiles. A clearer description of the procedures would undoubtedly increase the quality of papers in this area.

Development and Validation of New Discriminative Dissolution Method for Carvedilol Tablets

PubMed Central

Raju, V.; Murthy, K. V. R.

2011-01-01

The objective of the present study was to develop and validate a discriminative dissolution method for evaluation of carvedilol tablets. Different conditions such as type of dissolution medium, volume of dissolution medium and rotation speed of paddle were evaluated. The best in vitro dissolution profile was obtained using Apparatus II (paddle), 50 rpm, 900 ml of pH 6.8 phosphate buffer as dissolution medium. The drug release was evaluated by high-performance liquid chromatographic method. The dissolution method was validated according to current ICH and FDA guidelines using parameters such as the specificity, accuracy, precision and stability were evaluated and obtained results were within the acceptable range. The comparison of the obtained dissolution profiles of three different products were investigated using ANOVA-based, model-dependent and model-independent methods, results showed that there is significant difference between the products. The dissolution test developed and validated was adequate for its higher discriminative capacity in differentiating the release characteristics of the products tested and could be applied for development and quality control of carvedilol tablets. PMID:22923865

Dissolution of Simulated and Radioactive Savannah River Site High-Level Waste Sludges with Oxalic Acid & Citric Acid Solutions

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

STALLINGS, MARY

This report presents findings from tests investigating the dissolution of simulated and radioactive Savannah River Site sludges with 4 per cent oxalic acid and mixtures of oxalic and citric acid previously recommended by a Russian team from the Khlopin Radium Institute and the Mining and Chemical Combine (MCC). Testing also included characterization of the simulated and radioactive waste sludges. Testing results showed the following: Dissolution of simulated HM and PUREX sludges with oxalic and citric acid mixtures at SRTC confirmed general trends reported previously by Russian testing. Unlike the previous Russian testing six sequential contacts of a mixture of oxalicmore » acid citric acids at a 2:1 ratio (v/w) of acid to sludge did not produce complete dissolution of simulated HM and PUREX sludges. We observed that increased sludge dissolution occurred at a higher acid to sludge ratio, 50:1 (v/w), compared to the recommended ratio of 2:1 (v/w). We observed much lower dissolution of aluminum in a simulated HM sludge by sodium hydroxide leaching. We attribute the low aluminum dissolution in caustic to the high fraction of boehmite present in the simulated sludge. Dissolution of HLW sludges with 4 per cent oxalic acid and oxalic/citric acid followed general trends observed with simulated sludges. The limited testing suggests that a mixture of oxalic and citric acids is more efficient for dissolving HM and PUREX sludges and provides a more homogeneous dissolution of HM sludge than oxalic acid alone. Dissolution of HLW sludges in oxalic and oxalic/citric acid mixtures produced residual sludge solids that measured at higher neutron poison to equivalent 235U weight ratios than that in the untreated sludge solids. This finding suggests that residual solids do not present an increased nuclear criticality safety risk. Generally the neutron poison to equivalent 235U weight ratios of the acid solutions containing dissolved sludge components are lower than those in the untreated sludge solids. We recommend that these results be evaluated further to determine if these solutions contain sufficient neutron poisons. We observed low general corrosion rates in tests in which carbon steel coupons were contacted with solutions of oxalic acid, citric acid and mixtures of oxalic and citric acids. Wall thinning can be minimized by maintaining short contact times with these acid solutions. We recommend additional testing with oxalic and oxalic/citric acid mixtures to measure dissolution performance of sludges that have not been previously dried. This testing should include tests to clearly ascertain the effects of total acid strength and metal complexation on dissolution performance. Further work should also evaluate the downstream impacts of citric acid on the SRS High-Level Waste System (e.g., radiochemical separations in the Salt Waste Processing Facility and addition of organic carbon in the Saltstone and Defense Waste Processing facilities).« less

A novel dissolution media for testing drug release from a nanostructured polysaccharide-based colon specific drug delivery system: an approach to alternative colon media.

PubMed

Kotla, Niranjan G; Singh, Sima; Maddiboyina, Balaji; Sunnapu, Omprakash; Webster, Thomas J

2016-01-01

The aim of this study was to develop a novel microbially triggered and animal-sparing dissolution method for testing of nanorough polysaccharide-based micron granules for colonic drug delivery. In this method, probiotic cultures of bacteria present in the colonic region were prepared and added to the dissolution media and compared with the performance of conventional dissolution methodologies (such as media with rat cecal and human fecal media). In this study, the predominant species (such as Bacteroides, Bifidobacterium, Lactobacillus species, Eubacterium and Streptococcus) were cultured in 12% w/v skimmed milk powder and 5% w/v grade "A" honey. Approximately 10(10)-10(11) colony forming units m/L of probiotic culture was added to the dissolution media to test the drug release of polysaccharide-based formulations. A USP dissolution apparatus I/II using a gradient pH dissolution method was used to evaluate drug release from formulations meant for colonic drug delivery. Drug release of guar gum/Eudragit FS30D coated 5-fluorouracil granules was assessed under gastric and small intestine conditions within a simulated colonic environment involving fermentation testing with the probiotic culture. The results with the probiotic system were comparable to those obtained from the rat cecal and human fecal-based fermentation model, thereby suggesting that a probiotic dissolution method can be successfully applied for drug release testing of any polysaccharide-based oral formulation meant for colonic delivery. As such, this study significantly adds to the nanostructured biomaterials' community by elucidating an easier assay for colonic drug delivery.

Crushed tablets: does the administration of food vehicles and thickened fluids to aid medication swallowing alter drug release?

PubMed

Manrique, Yady J; Lee, Danielle J; Islam, Faiza; Nissen, Lisa M; Cichero, Julie A Y; Stokes, Jason R; Steadman, Kathryn J

2014-01-01

To evaluate the influence of co-administered vehicles on in vitro dissolution in simulated gastric fluid of crushed immediate release tablets as an indicator for potential drug bioavailability compromise. Release and dissolution of crushed amlodipine, atenolol, carbamazepine and warfarin tablets were tested with six foods and drinks that are frequently used in the clinical setting as mixers for crushed medications (water, orange juice, honey, yoghurt, strawberry jam and water thickened with Easythick powder) in comparison to whole tablets. Five commercial thickening agents (Easythick Advanced, Janbak F, Karicare, Nutilis, Viscaid) at three thickness levels were tested for their effect on the dissolution of crushed atenolol tablets. Atenolol dissolution was unaffected by mixing crushed tablets with thin fluids or food mixers in comparison to whole tablets or crushed tablets in water, but amlodipine was delayed by mixing with jam. Mixing crushed warfarin and carbamazepine tablets with honey, jam or yoghurt caused them to resemble the slow dissolution of whole tablets rather than the faster dissolution of crushed tablets in water or orange juice. Crushing and mixing any of the four medications with thickened water caused a significant delay in dissolution. When tested with atenolol, all types of thickening agents at the greatest thickness significantly restricted dissolution, and products that are primarily based on xanthan gum also delayed dissolution at the intermediate thickness level. Dissolution testing, while simplistic, is a widely used and accepted method for comparing drug release from different formulations as an indicator for in vivo bioavailability. Thickened fluids have the potential to retard drug dissolution when used at the thickest levels. These findings highlight potential clinical implications of the addition of these agents to medications for the purpose of dose delivery and indicate that further investigation of thickened fluids and their potential to influence therapeutic outcomes is warranted.

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets

PubMed Central

Anumolu, P. D.; Sunitha, G.; Bindu, S. Hima; Satheshbabu, P. R.; Subrahmanyam, C. V. S.

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias. PMID:26180277

Development and Validation of Discriminating and Biorelevant Dissolution Test for Lornoxicam Tablets.

PubMed

Anumolu, P D; Sunitha, G; Bindu, S Hima; Satheshbabu, P R; Subrahmanyam, C V S

2015-01-01

The establishment of biorelevant and discriminating dissolution procedure for drug products with limited water solubility is a useful technique for qualitative forecasting of the in vivo behavior of formulations. It also characterizes the drug product performance in pharmaceutical development. Lornoxicam, a BCS class-II drug is a nonsteroidal antiinflammatory drug of the oxicam class, has no official dissolution media available in the literature. The objective of present work was to develop and validate a discriminating and biorelevant dissolution test for lornoxicam tablet dosage forms. To quantify the lornoxicam in dissolution samples, UV spectrophotometric method was developed using 0.01M sodium hydroxide solution as solvent at λma×376 nm. After evaluation of saturation solubility, dissolution, sink conditions and stability of lornoxicam bulk drug in different pH solutions and biorelevant media, the dissolution method was optimized using USP paddle type apparatus at 50 rpm rotation speed and 500 ml simulated intestinal fluid as discriminating and biorelevant dissolution medium. The similarity factor (f2) were investigated for formulations with changes in composition and manufacturing variations, values revealed that dissolution method having discriminating power and method was validated as per standard guidelines. The proposed dissolution method can be effectively applied for routine quality control in vitro dissolution studies of lornoxicam in tablets and helpful to pharmacopoeias.

Developing dissolution testing methodologies for extended-release oral dosage forms with supersaturating properties. Case example: Solid dispersion matrix of indomethacin.

PubMed

Tajiri, Tomokazu; Morita, Shigeaki; Sakamoto, Ryosaku; Mimura, Hisahi; Ozaki, Yukihiro; Reppas, Christos; Kitamura, Satoshi

2015-07-25

The objective of this study was to develop an in vitro dissolution test method with discrimination ability for an extended-release solid dispersion matrix of a lipophilic drug using the United States Pharmacopeia (USP) Apparatus 4, flow-through cell apparatus. In the open-loop configuration, the sink condition was maintained by manipulating the flow rate of the dissolution medium. To evaluate the testing conditions, the drug release mechanism from an extended-release solid dispersion matrix containing hydrophobic and hydrophilic polymers was investigated. As the hydroxypropyl methylcellulose (HPMC) maintained concentrations of indomethacin higher than the solubility in a dissolution medium, the release of HPMC into the dissolution medium was also quantified using size-exclusion chromatography. We concluded that the USP Apparatus 4 is suitable for application to an in vitro dissolution method for orally administered extended-release solid dispersion matrix formulations containing poorly water-soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

Rapid analysis of drug dissolution by paper spray ionization mass spectrometry.

PubMed

Liu, Yang; Liu, Ning; Zhou, Ya-Nan; Lin, Lan; He, Lan

2017-03-20

With a great quantity of solid dosage tested by dissolution technology, developing a rapid and sensitive method to access the content of drug within dissolution media is highly desired by analysts and scientists. Traditionally, dissolution media is not compatible with mass spectrometry since the inorganic salts in the media might damage the mass spectrometer. Here, paper spray ionization mass spectrometry (PSI-MS), one of the ambient mass spectrometry technologies, is developed to characterize the content of drugs in dissolution media. The porous structure of paper can effectively retain salts from entering mass spectrometer. This makes the measurement of drug content within dissolution media by mass spectrometer possible. After the experimental parameters were optimized, calibration curves of model drugs - enalapril, quinapril and benazepril were established by using corresponding deuterated internal standards. PSI-MS was then deployed to characterize the content of enalapril from the dissolution testing of enalapril tablets. The results from PSI-MS are comparable to those from HPLC characterization. More importantly, the analysis time of 6 samples is shortened from 90min to 6min. Detection limit of enalapril maleate tablets by PSI-MS is 1/300 of LC. PSI-MS is rapid, sensitive and accurate in analyzing drug content from dissolution tests. Copyright © 2016 Elsevier B.V. All rights reserved.

Physiological Parameters for Oral Delivery and In vitro Testing

PubMed Central

Mudie, Deanna M.; Amidon, Gordon L.; Amidon, Gregory E.

2010-01-01

Pharmaceutical solid oral dosage forms must undergo dissolution in the intestinal fluids of the gastrointestinal tract before they can be absorbed and reach the systemic circulation. Therefore, dissolution is a critical part of the drug-delivery process. The rate and extent of drug dissolution and absorption depend on the characteristics of the active ingredient as well as properties of the dosage form. Just as importantly, characteristics of the physiological environment such as buffer species, pH, bile salts, gastric emptying rate, intestinal motility, and hydrodynamics can significantly impact dissolution and absorption. While significant progress has been made since 1970 when the first compendial dissolution test was introduced (USP Apparatus 1), current dissolution testing does not take full advantage of the extensive physiologic information that is available. For quality control purposes, where the question is one of lot-to-lot consistency in performance, using nonphysiologic test conditions that match drug and dosage form properties with practical dissolution media and apparatus may be appropriate. However, where in vitro – in vivo correlations are desired, it is logical to consider and utilize knowledge of the in vivo condition. This publication critically reviews the literature that is relevant to oral human drug delivery. Physiologically relevant information must serve as a basis for the design of dissolution test methods and systems that are more representative of the human condition. As in vitro methods advance in their physiological relevance, better in vitro - in vivo correlations will be possible. This will, in turn, lead to in vitro systems that can be utilized to more effectively design dosage forms that have improved and more consistent oral bioperformance. PMID:20822152

Flow-injection system for automated dissolution testing of isoniazid tablets with chemiluminescence detection.

PubMed

Li, B; Zhang, Z; Liu, W

2001-05-30

A simple and sensitive flow-injection chemiluminescence (CL) system for automated dissolution testing is described and evaluated for monitoring of dissolution profiles of isoniazid tablets. The undissolved suspended particles in the dissolved solution were eliminated via on-line filter. The novel CL system of KIO(4)-isoniazid was also investigated. The sampling frequency of the system was 120 h(-1). The dissolution profiles of isoniazid fast-release tablets from three sources were determined, which demonstrates the stability, great sensitivity, large dynamic measuring range and robustness of the system.

Regulatory Perspectives on Strength-Dependent Dissolution Profiles and Biowaiver Approaches for Immediate Release (IR) Oral Tablets in New Drug Applications.

PubMed

Suarez-Sharp, Sandra; Delvadia, Poonam R; Dorantes, Angelica; Duan, John; Externbrink, Anna; Gao, Zongming; Ghosh, Tapash; Miksinski, Sarah Pope; Seo, Paul

2016-05-01

Dissolution profile comparisons are used by the pharmaceutical industry to assess the similarity in the dissolution characteristics of two formulations to decide whether the implemented changes, usually minor/moderate in nature, will have an impact on the in vitro/in vivo performance of the drug product. When similarity testing is applied to support the approval of lower strengths of the same formulation, the traditional approach for dissolution profile comparison is not always applicable for drug products exhibiting strength-dependent dissolution and may lead to incorrect conclusions about product performance. The objective of this article is to describe reasonable biopharmaceutic approaches for developing a biowaiver strategy for low solubility, proportionally similar/non-proportionally similar in composition immediate release drug products that exhibit strength-dependent dissolution profiles. The paths highlighted in the article include (1) approaches to address biowaiver requests, such as the use of multi-unit dissolution testing to account for sink condition differences between the higher and lower strengths; (2) the use of a single- vs. strength-dependent dissolution method; and (3) the use of single- vs. strength-dependent dissolution acceptance criteria. These approaches are cost- and time-effective and can avoid unnecessary bioequivalence studies.

Effects of Pump Pulsation on Hydrodynamic Properties and Dissolution Profiles in Flow-Through Dissolution Systems (USP 4).

PubMed

Yoshida, Hiroyuki; Kuwana, Akemi; Shibata, Hiroko; Izutsu, Ken-Ichi; Goda, Yukihiro

2016-06-01

To clarify the effects of pump pulsation and flow-through cell (FTC) dissolution system settings on the hydrodynamic properties and dissolution profiles of model formulations. Two FTC systems with different cell temperature control mechanisms were used. Particle image velocimetry (PIV) was used to analyze the hydrodynamic properties of test solutions in the flow-through dissolution test cell. Two pulsation pumps (semi-sine, full-sine) and a non-pulsatile pump were used to study the effects of varied flows on the dissolution profiles of United States Pharmacopeia standard tablets. PIV analysis showed periodic changes in the aligned upward fluid flow throughout the dissolution cell that was designed to reduce the temperature gradient during pump pulsation (0.5 s/pulse). The maximum instantaneous flow from the semi-sine pump was higher than that of the full-sine pump under all conditions. The flow from the semi-sine wave pump showed faster dissolution of salicylic acid and prednisone tablets than those from other pumps. The semi-sine wave pump flow showed similar dissolution profiles in the two FTC systems. Variations in instantaneous fluid flow caused by pump pulsation that meets the requirements of pharmacopoeias are a factor that affects the dissolution profiles of tablets in FTC systems.

Hydrodynamic investigation of USP dissolution test apparatus II.

PubMed

Bai, Ge; Armenante, Piero M; Plank, Russell V; Gentzler, Michael; Ford, Kenneth; Harmon, Paul

2007-09-01

The USP Apparatus II is the device commonly used to conduct dissolution testing in the pharmaceutical industry. Despite its widespread use, dissolution testing remains susceptible to significant error and test failures, and limited information is available on the hydrodynamics of this apparatus. In this work, laser-Doppler velocimetry (LDV) and computational fluid dynamics (CFD) were used, respectively, to experimentally map and computationally predict the velocity distribution inside a standard USP Apparatus II under the typical operating conditions mandated by the dissolution test procedure. The flow in the apparatus is strongly dominated by the tangential component of the velocity. Secondary flows consist of an upper and lower recirculation loop in the vertical plane, above and below the impeller, respectively. A low recirculation zone was observed in the lower part of the hemispherical vessel bottom where the tablet dissolution process takes place. The radial and axial velocities in the region just below the impeller were found to be very small. This is the most critical region of the apparatus since the dissolving tablet will likely be at this location during the dissolution test. The velocities in this region change significantly over short distances along the vessel bottom. This implies that small variations in the location of the tablet on the vessel bottom caused by the randomness of the tablet descent through the liquid are likely to result in significantly different velocities and velocity gradients near the tablet. This is likely to introduce variability in the test. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.

Modeling solid-state transformations occurring in dissolution testing.

PubMed

Laaksonen, Timo; Aaltonen, Jaakko

2013-04-15

Changes in the solid-state form can occur during dissolution testing of drugs. This can often complicate interpretation of results. Additionally, there can be several mechanisms through which such a change proceeds, e.g. solvent-mediated transformation or crystal growth within the drug material itself. Here, a mathematical model was constructed to study the dissolution testing of a material, which undergoes such changes. The model consisted of two processes: the recrystallization of the drug from a supersaturated liquid state caused by the dissolution of the more soluble solid form and the crystal growth of the stable solid form at the surface of the drug formulation. Comparison to experimental data on theophylline dissolution showed that the results obtained with the model matched real solid-state changes and that it was able to distinguish between cases where the transformation was controlled either by solvent-mediated crystallization or solid-state crystal growth. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of a discriminative biphasic in vitro dissolution test and correlation with in vivo pharmacokinetic studies for differently formulated racecadotril granules.

PubMed

Deng, Jia; Staufenbiel, Sven; Hao, Shilei; Wang, Bochu; Dashevskiy, Andriy; Bodmeier, Roland

2017-06-10

The purpose of this study was to discriminate the release behavior from three differently formulated racecadotril (BCS II) granules and to establish an in vitro-in vivo correlation. Three granule formulations of the lipophilic drug were prepared with equivalent composition but prepared with different manufacturing processes (dry granulation, wet granulation with or without binder). In vitro release of the three granules was investigated using a biphasic dissolution system (phosphate buffer pH6.8 and octanol) and compared to the conventional single phase USP II dissolution test performed under sink and non-sink conditions. In vivo studies with each granule formulation were performed in rats. Interestingly, the granule formulations exhibited pronouncedly different behavior in the different dissolution systems depending on different wetting and dissolution conditions. Single phase USP II dissolution tests lacked discrimination. In contrast, remarkable discrimination between the granule formulations was observed in the octanol phase of biphasic dissolution system with a rank order of release from granules prepared by wet granulation with binder>wet granulation without binder>dry granulation. This release order correlated well with the wettability of these granules. An excellent correlation was also established between in vitro release in the octanol phase of the biphasic test and in vivo data (R 2 =0.999). Compared to conventional dissolution methods, the biphasic method provides great potential to discriminate between only minor formulation and process changes within the same dosage form for poorly soluble drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Dissolution of lanthanide alumino-silicate oxynitride glasses

NASA Astrophysics Data System (ADS)

Bois, L.; Barré, N.; Guillopé, S.; Guittet, M. J.; Gautier-Soyer, M.; Duraud, J. P.; Trocellier, P.; Verdier, P.; Laurent, Y.

2000-01-01

The aqueous corrosion behavior of lanthanide aluminosilicate glasses has been studied under static conditions ( T=96°C, duration=1 and 3 months, glass surface area/leachate volume, S/ V=0.3 cm -1) by means of solution and solid analyses. It was found that these glasses exhibit a high chemical durability. The influence of yttrium, magnesium and nitrogen, which are supposed to improve the mechanical properties, on the chemical durability, has been investigated. After a one-month experiment, lanthanum and yttrium releases were found to be about 10 -7 mol l -1, while silicon and aluminum releases were about 10 -5 mol l -1. Yttrium seems to improve the chemical durability. The presence of nitrogen does not seem to modify the glass constituents releases, but seems to improve the surface state of the altered glass. XPS experiments reveal that lanthanum and yttrium are more concentrated near the surface (20-30 Å) of the glass after the leaching test.

Statistical Considerations Concerning Dissimilar Regulatory Requirements for Dissolution Similarity Assessment. The Example of Immediate-Release Dosage Forms.

PubMed

Jasińska-Stroschein, Magdalena; Kurczewska, Urszula; Orszulak-Michalak, Daria

2017-05-01

When performing in vitro dissolution testing, especially in the area of biowaivers, it is necessary to follow regulatory guidelines to minimize the risk of an unsafe or ineffective product being approved. The present study examines model-independent and model-dependent methods of comparing dissolution profiles based on various compared and contrasted international guidelines. Dissolution profiles for immediate release solid oral dosage forms were generated. The test material comprised tablets containing several substances, with at least 85% of the labeled amount dissolved within 15 min, 20-30 min, or 45 min. Dissolution profile similarity can vary with regard to the following criteria: time point selection (including the last time point), coefficient of variation, and statistical method selection. Variation between regulatory guidance and statistical methods can raise methodological questions and result potentially in a different outcome when reporting dissolution profile testing. The harmonization of existing guidelines would address existing problems concerning the interpretation of regulatory recommendations and research findings. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Hydrodynamics-induced variability in the USP apparatus II dissolution test.

PubMed

Baxter, Jennifer L; Kukura, Joseph; Muzzio, Fernando J

2005-03-23

The USP tablet dissolution test is an analytical tool used for the verification of drug release processes and formulation selection within the pharmaceutical industry. Given the strong impact of this test, it is surprising that operating conditions and testing devices have been selected empirically. In fact, the flow phenomena in the USP test have received little attention in the past. An examination of the hydrodynamics in the USP apparatus II shows that the device is highly vulnerable to mixing problems that can affect testing performance and consistency. Experimental and computational techniques reveal that the flow field within the device is not uniform, and dissolution results can vary dramatically with the position of the tablet within the vessel. Specifically, computations predict sharp variations in the shear along the bottom of the vessel where the tablet is most likely to settle. Experiments in which the tablet location was carefully controlled reveal that the variation of shear within the testing device can affect the measured dissolution rate.

Indomethacin-Kollidon VA64 Extrudates: A Mechanistic Study of pH-Dependent Controlled Release.

PubMed

Tres, Francesco; Treacher, Kevin; Booth, Jonathan; Hughes, Leslie P; Wren, Stephen A C; Aylott, Jonathan W; Burley, Jonathan C

2016-03-07

Because of its weakly acidic nature (pKa of 4.5), indomethacin presents an aqueous solubility that significantly increases when changing from acidic to neutral/alkaline pH (1.5 μg/mL at pH 1.2 and 105.2 μg/mL at pH 7.4). We have therefore investigated the impact of the dissolution medium pH on the dissolution performance of indomethacin:Kollidon VA64 extrudates. The impact of the drug loading on the dissolution properties of these systems was also examined (5%, 15%, 30%, 50%, 70%, and 90% drug loading). Time-resolved Raman spectroscopy along with in-line UV-vis spectrophotometry was employed to directly relate changes in dissolution behavior to physicochemical changes that occur to the extrudate during the test. The dissolution tests were performed in pH 2 HCl (to mimic the stomach conditions), and this was then switched during the experiment to pH 6.8 phosphate buffer (to simulate the poststomach conditions). The rotating disc dissolution rate test was also used to simultaneously measure the dissolution rate of both the drug and the polymer. We found that in pH 2 HCl buffer, for the 15% or higher drug-loaded extrudates, Kollidon VA64 preferentially dissolves from the exterior of the compact leaving an amorphous drug-rich hydrophobic shell, which, similarly to an enteric coating, inhibits the drug release. The in situ formation of an enteric coating has been previously hypothesized, and this has been the first time that is directly observed in a pH-variable dissolution test. The dissolution medium switch to pH 6.8 phosphate buffer, due to the large increase of the aqueous solubility of indomethacin at this pH, leads to rapid dissolution of the material forming the coating and therefore total drug release. In contrast, the 5% extrudate is fully hydrated and quickly dissolves at low pH pointing to a dissolution performance dependent on highly water-soluble Kollidon VA64.

Oxidation and the Effects of High Temperature Exposures on Notched Fatigue Life of an Advanced Powder Metallurgy Disk Superalloy

NASA Technical Reports Server (NTRS)

Sudbrack, Chantal K.; Draper, Susan L.; Gorman, Timothy T.; Telesman, Jack; Gab, Timothy P.; Hull, David R.

2012-01-01

Oxidation and the effects of high temperature exposures on notched fatigue life were considered for a powder metallurgy processed supersolvus heat-treated ME3 disk superalloy. The isothermal static oxidation response at 704 C, 760 C, and 815 C was consistent with other chromia forming nickel-based superalloys: a TiO2-Cr2O3 external oxide formed with a branched Al2O3 internal subscale that extended into a recrystallized - dissolution layer. These surface changes can potentially impact disk durability, making layer growth rates important. Growth of the external scales and dissolution layers followed a cubic rate law, while Al2O3 subscales followed a parabolic rate law. Cr- rich M23C6 carbides at the grain boundaries dissolved to help sustain Cr2O3 growth to depths about 12 times thicker than the scale. The effect of prior exposures was examined through notched low cycle fatigue tests performed to failure in air at 704 C. Prior exposures led to pronounced debits of up to 99 % in fatigue life, where fatigue life decreased inversely with exposure time. Exposures that produced roughly equivalent 1 m thick external scales at the various isotherms showed statistically equivalent fatigue lives, establishing that surface damage drives fatigue debit, not exposure temperature. Fractographic evaluation indicated the failure mode for the pre-exposed specimens involved surface crack initiations that shifted with exposure from predominately single intergranular initiations with transgranular propagation to multi-initiations from the cracked external oxide with intergranular propagation. Weakened grain boundaries at the surface resulting from the M23C6 carbide dissolution are partially responsible for the intergranular cracking. Removing the scale and subscale while leaving a layer where M23C6 carbides were dissolved did not lead to a significant fatigue life improvement, however, also removing the M23C6 carbide dissolution layer led to nearly full recovery of life, with a transgranular initiation typical to that observed in unexposed specimens.

Evaluating bioequivalence of meloxicam tablets: is in-vitro dissolution test overdiscriminating?

PubMed

Jin, Chan; Zhao, Chenyao; Shen, Dachao; Dong, Wenxiang; Liu, Hongzhuo; He, Zhonggui

2018-02-01

The aim of the study was to assess the impact of the differences in dissolution profiles of meloxicam tablets on the in-vivo bioavailability parameters after oral administration. Compare in-vitro dissolution testing in the recommended media to evaluate in-vivo bioequivalence outcomes for the Biopharmaceutics Classification System Class II weak acidic drugs. Nine Beagle dogs received a single oral administration of each formulation (7.5 mg) in a three-way crossover design. The dissolution of meloxicam from both test products showed marked differences with that from the reference tablet in pH 1.0, 4.5 and 6.8 media at 50 or 75 rpm. Both formulations exhibiting slow or fast dissolution were then compared with the reference product for in-vivo bioequivalence study. Both products were bioequivalent with the reference tablet in either extent or rate of oral absorption. It indicated that the dissolution profiles which discriminated between the formulations in vitro did not accurately predict the in-vivo bioequivalence outcomes. Comparative dissolution profiles using similarity factor (f 2 ) in the recommended media should be relaxed to fulfil the requirements for the development, scale-up and postapproval changes to immediate release oral solid dosage forms of meloxicam. © 2017 Royal Pharmaceutical Society.

Accelerated dissolution testing for controlled release microspheres using the flow-through dissolution apparatus.

PubMed

Collier, Jarrod W; Thakare, Mohan; Garner, Solomon T; Israel, Bridg'ette; Ahmed, Hisham; Granade, Saundra; Strong, Deborah L; Price, James C; Capomacchia, A C

2009-01-01

Theophylline controlled release capsules (THEO-24 CR) were used as a model system to evaluate accelerated dissolution tests for process and quality control and formulation development of controlled release formulations. Dissolution test acceleration was provided by increasing temperature, pH, flow rate, or adding surfactant. Electron microscope studies on the theophylline microspheres subsequent to each experiment showed that at pH values of 6.6 and 7.6 the microspheres remained intact, but at pH 8.6 they showed deterioration. As temperature was increased from 37-57 degrees C, no change in microsphere integrity was noted. Increased flow rate also showed no detrimental effect on integrity. The effect of increased temperature was determined to be the statistically significant variable.

The Relationship Between the Evolution of an Internal Structure and Drug Dissolution from Controlled-Release Matrix Tablets.

PubMed

Kulinowski, Piotr; Hudy, Wiktor; Mendyk, Aleksander; Juszczyk, Ewelina; Węglarz, Władysław P; Jachowicz, Renata; Dorożyński, Przemysław

2016-06-01

In the last decade, imaging has been introduced as a supplementary method to the dissolution tests, but a direct relationship of dissolution and imaging data has been almost completely overlooked. The purpose of this study was to assess the feasibility of relating magnetic resonance imaging (MRI) and dissolution data to elucidate dissolution profile features (i.e., kinetics, kinetics changes, and variability). Commercial, hydroxypropylmethyl cellulose-based quetiapine fumarate controlled-release matrix tablets were studied using the following two methods: (i) MRI inside the USP4 apparatus with subsequent machine learning-based image segmentation and (ii) dissolution testing with piecewise dissolution modeling. Obtained data were analyzed together using statistical data processing methods, including multiple linear regression. As a result, in this case, zeroth order release was found to be a consequence of internal structure evolution (interplay between region's areas-e.g., linear relationship between interface and core), which eventually resulted in core disappearance. Dry core disappearance had an impact on (i) changes in dissolution kinetics (from zeroth order to nonlinear) and (ii) an increase in variability of drug dissolution results. It can be concluded that it is feasible to parameterize changes in micro/meso morphology of hydrated, controlled release, swellable matrices using MRI to establish a causal relationship between the changes in morphology and drug dissolution. Presented results open new perspectives in practical application of combined MRI/dissolution to controlled-release drug products.

Development and validation of a dissolution test for lodenafil carbonate based on in vivo data.

PubMed

Codevilla, Cristiane Franco; Castilhos, Tamara dos Santos; Cirne, Carolina Araújo; Froehlich, Pedro Eduardo; Bergold, Ana Maria

2014-04-01

Lodenafil carbonate is a phosphodiesterase type 5 inhibitor used for the treatment of erectile dysfunction. Currently, there is no dissolution test reported for lodenafil carbonate and this drug is not listed in any pharmacopoeia. The present study focused on the development and validation of a dissolution test for lodenafil carbonate tablets, using a simulated absorption profile based on in vivo data. The appropriate conditions were determined after testing sink conditions. Different conditions as medium, surfactant concentration and rotation speed were evaluated. The percentage of dose absorbed was calculated by deconvolution, using the Wagner-Nelson method. According to the obtained results, the use of 0.1 M HCl + 1.5% SLS (900 mL, at 37 + 0.5 °C) as the dissolution medium, paddles at 25 rpm were considered adequate. The samples were quantified by UV spectroscopy at 295 nm and the validation was performed according to international guidelines. The method showed specificity, linearity, accuracy and precision, within the acceptable range. Kinetics of drug release was better described by the first-order model. The proposed dissolution test can be used for the routine quality control of lodenafil carbonate in tablets.

Effect of drug loading method against drug dissolution mechanism of encapsulated amoxicillin trihydrate in matrix of semi-IPN chitosan-poly(N-vinylpyrrolidone) hydrogel with KHCO3 as pore forming agent in floating drug delivery system

NASA Astrophysics Data System (ADS)

Fimantari, Khansa; Budianto, Emil

2018-04-01

Helicobacterpylori infection can be treated using trihydrate amoxicillin. However, this treatment is not effective enough, as the conventional dosage treatment has a relatively short retention time in the human stomach. In the present study, the amoxicillin trihydrate drug will be encapsulated into a semi-IPN K-PNVP hydrogel matrix with 7,5% KHCO3 as a pore-forming agent. The encapsulated drug is tested with in vitro method to see the efficiency of its encapsulation and dissolution. The hydrogel in situ loading produces an encapsulation efficiency value. The values of the encapsulation efficiency are 95% and 98%, while post loading hydrogel yields an encapsulation efficiency value is 77% and the dissolution is 84%. The study of drug dissolution mechanism was done by using mathematical equation model to know its kinetics and its mechanism of dissolution. The post loading hydrogel was done by using thefirst-order model, while hydrogel in situ loading used Higuchi model. The Korsmeyer-Peppas model shows that post loading hydrogel dissolution mechanism is a mixture of diffusion and erosion, and in situ loading hydrogel in the form of diffusion. It is supported by the results of hydrogel characterization, before and after dissolution test with an optical microscope. The results of the optical microscope show that the hydrogel surface before and after the dissolution tested for both methods shows the change becomes rougher.

Discriminative Dissolution Method for Benzoyl Metronidazole Oral Suspension.

PubMed

da Silva, Aline Santos; da Rosa Silva, Carlos Eduardo; Paula, Fávero Reisdorfer; da Silva, Fabiana Ernestina Barcellos

2016-06-01

A dissolution method for benzoyl metronidazole (BMZ) oral suspensions was developed and validated using a high-performance liquid chromatography (HPLC) method. After determination of sink conditions, dissolution profiles were evaluated using different dissolution media and agitation speeds. The sample insertion mode in dissolution media was also evaluated. The best conditions were obtained using a paddle, 50 rpm stirring speed, simulated gastric fluid (without pepsin) as the dissolution medium, and sample insertion by a syringe. These conditions were suitable for providing sink conditions and discriminatory power between different formulations. Through the tested conditions, the results can be considered specific, linear, precise, accurate, and robust. The dissolution profiles of five samples were compared using the similarity factor (f 2) and dissolution efficiency. The dissolution kinetics were evaluated and described by the Weibull model. Whereas there is no monograph for this pharmaceutical formulation, the dissolution method proposed can be considered suitable for quality control and dissolution profile comparison of different commercial formulations.

Development and validation of dissolution study of sustained release dextromethorphan hydrobromide tablets.

PubMed

Rajan, Sekar; Colaco, Socorrina; Ramesh, N; Meyyanathan, Subramania Nainar; Elango, K

2014-02-01

This study describes the development and validation of dissolution tests for sustained release Dextromethorphan hydrobromide tablets using an HPLC method. Chromatographic separation was achieved on a C18 column utilizing 0.5% triethylamine (pH 7.5) and acetonitrile in the ratio of 50:50. The detection wavelength was 280 nm. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The suitable conditions were clearly decided after testing sink conditions, dissolution medium and agitation intensity. The most excellent dissolution conditions tested, for the Dextromethorphan hydrobromide was applied to appraise the dissolution profiles. The method was validated and response was found to be linear in the drug concentration range of 10-80 microg mL(-1). The method was established to have sufficient intermediate precision as similar separation was achieved on another instrument handled by different operators. Mean Recovery was 101.82%. Intra precisions for three different concentrations were 1.23, 1.10 0.72 and 1.57, 1.69, 0.95 and inter run precisions were % RSD 0.83, 1.36 and 1.57%, respectively. The method was successfully applied for dissolution study of the developed Dextromethorphan hydrobromide tablets.

Development of a Suitable Dissolution Method for the Combined Tablet Formulation of Atorvastatin and Ezetimibe by RP-LC Method.

PubMed

Ozkan Cansel, Kose; Ozgur, Esim; Sevinc, Kurbanoglu; Ayhan, Savaser; Ozkan, Sibel A; Yalcin, Ozkan

2016-01-01

Pharmaceutical preparations of ezetimibe and atorvastatin are generally used to regulate the lipid level in blood. It decreases the secondary events for patients with high cholesterol and clinical cardiovascular disease such as non-fatal or fatal heart attack. There is no any pharmacopoeia method available for the dissolution testing recommended by the FDA. Development of dissolution tests method is very critical parameter especially for the pharmaceutical preparations that contain Class II drugs (slightly soluble, good permeable). In the proposed method, the effects of pH and surfactant on the dissolution of poorly water soluble combined drug therapy with a different pKa values in an in vitro environment is investigated. The content of our study was designed to answer these open-ended questions. The optimized test conditions achieved under sink conditions with USP apparatus 2 at a paddle rotation speed of 75 rpm and 900 ml in 0.01 M Acetate buffer (pH= 6.8) containing 0.45% SDS as a dissolution medium. Quantification of dissolution samples were analyzed with a new fully validated RP-LC method with UV detection at 242 nm.

Dissolution of pulp tissue by aqueous solution of chlorhexidine digluconate and chlorhexidine digluconate gel.

PubMed

Okino, L A; Siqueira, E L; Santos, M; Bombana, A C; Figueiredo, J A P

2004-01-01

To evaluate the activity of various root canal irrigants on bovine pulp tissue. The irrigants tested were: 0.5, 1.0 and 2.5% sodium hypochlorite; 2% aqueous solution of chlorhexidine digluconate; 2% chlorhexidine digluconate gel (Natrosol); and distilled water as control. Bovine pulp fragments were weighed and placed in contact with 20 mL of each tested substance in a centrifuge at 150 r.p.m. until total dissolution. Dissolution speed was calculated by dividing pulp weight by dissolution time. Statistical analysis was performed using the Kruskal-Wallis test. Distilled water and both solutions of chlorhexidine did not dissolve the pulp tissue within 6 h. Mean dissolution speeds for 0.5, 1.0 and 2.5% sodium hypochlorite solutions were 0.31, 0.43 and 0.55 mg min(-1), respectively. The solvent ability of chlorhexidine solutions was similar to that of distilled water. The results for sodium hypochlorite solutions, chlorhexidine solutions and distilled water were statistically different (P>0.01). Both chlorhexidine preparations and distilled water were not able to dissolve pulp tissue. All sodium hypochlorite solutions were efficient in dissolving pulp tissue; the dissolution speed varied with the concentration of the solution.

Biotic and abiotic interactions in aquatic microcosms determine fate and toxicity of Ag nanoparticles. Part 1. Aggregation and dissolution.

PubMed

Unrine, Jason M; Colman, Benjamin P; Bone, Audrey J; Gondikas, Andreas P; Matson, Cole W

2012-07-03

To better understand their fate and toxicity in aquatic environments, we compared the aggregation and dissolution behavior of gum arabic (GA) and polyvinylpyrrolidone (PVP) coated Ag nanoparticles (NPs) in aquatic microcosms. There were four microcosm types: surface water; water and sediment; water and aquatic plants; or water, sediment, and aquatic plants. Dissolution and aggregation behavior of AgNPs were examined using ultracentrifugation, ultrafiltration, and asymmetrical flow field flow fractionation coupled to ultraviolet-visible spectroscopy, dynamic and static laser light scattering, and inductively coupled plasma mass spectrometry. Plants released dissolved organic matter (DOM) into the water column either through active or passive processes in response to Ag exposure. This organic matter fraction readily bound Ag ions. The plant-derived DOM had the effect of stabilizing PVP-AgNPs as primary particles, but caused GA-AgNPs to be removed from the water column, likely by dissolution and binding of released Ag ions on sediment and plant surfaces. The destabilization of the GA-AgNPs also corresponded with X-ray absorption near edge spectroscopy results which suggest that 22-28% of the particulate Ag was associated with thiols and 5-14% was present as oxides. The results highlight the potential complexities of nanomaterial behavior in response to biotic and abiotic modifications in ecosystems, and may help to explain differences in toxicity of Ag observed in realistic exposure media compared to simplified laboratory exposures.

Reaction processes and permeability changes during CO2-rich brine flow through fractured Portland cement

NASA Astrophysics Data System (ADS)

Abdoulghafour, H.; Luquot, L.; Gouze, P.

2012-12-01

So far, cement alteration was principally studied experimentally using batch reactor (with static or renewed fluid). All exhibit similar carbonation mechanisms. The acidic solution, formed by the dissolution of the CO2 into the pore water or directly surrounding the cement sample, diffuses into the cement and induces dissolution reactions of the cement hydrates in particular portlandite and CSH. The calcium released by the dissolution of these calcium bearing phases combining with carbonate ions of the fluid forms calcium carbonates. The cement pH, initially around 13, falls to values where carbonate ion is the most dominant element (pH ~ 9), then CaCO3 phases can precipitate. These studies mainly associate carbonation process with a reduction of porosity and permeability. Indeed an increase of volume (about 10%) is expected during the formation of calcite from portlandite (equation 2) assuming a stoichiometric reaction. Here we investigated the cement alteration mechanisms in the frame of a controlled continuous renewal of CO2-rich fluid in a fracture. This situation is that expected when seepage is activated by the mechanical failure of the cement material that initially seals two layers of distinctly different pressure: the storage reservoir and the aquifer above the caprock, for instance. We study the effect of flow rates from quasi-static flow to higher flow rates for well-connected fractures. In the quasi-static case we observed an extensive conversion of portlandite (Ca(OH)2) to calcite in the vicinity of the fracture similar to that observed in the published batch experiments. Eventually, the fracture was almost totally healed. The experiments with constant flow revealed a different behaviour triggered by the continuous renewing of the reactants and withdrawal of reaction products. We showed that calcite precipitation is more efficient for low flow rate. With intermediate flow rate, we measured that permeability increases slowly at the beginning of the experiment and then remains constant due to calcite precipitation in replacement of CSH and CH into fracture border. With higher flow rate, we measured a constant permeability which can be explained by the development of a highly hydrated Si-rich zone which maintains the initial fracture aperture during all over the experiment while noticeable mass is released from the sample. These preliminary results emphasize that more complex behaviours than that envisaged from batch experiments may take place in the vicinity of flowing fractures. We demonstrated that if only micro-cracks appear in the cement well, carbonation reaction may heal these micro-cracks and mitigate leakage whereas conductive fractures allowing high flow may represent a risk of perennial leakage because the net carbonation process, including the calcite precipitation and its subsequent re-dissolution, is sufficiently to heal the fracture. However, the precipitation of Si-rich amorphous phases may maintain the initial fracture aperture and limit the leakage rate. Keywords: leakage, cement alteration, flow rate, fracture, permeability changes, reaction processes.

Fractured cement reactivity during CO2-rich brine leakage: Consequences on hydrodynamic and structural properties

NASA Astrophysics Data System (ADS)

abdelghafour, H.; Luquot, L.; Gouze, P.

2013-12-01

So far, cement alteration was principally studied experimentally using batch reactor (with static or renewed fluid). All exhibit similar carbonation mechanisms. The acidic solution, formed by the dissolution of the CO2 into the pore water or directly surrounding the cement sample, diffuses into the cement and induces dissolution reactions of the cement hydrates in particular portlandite and CSH. The calcium released by the dissolution of these calcium bearing phases combining with carbonate ions of the fluid forms calcium carbonates. The cement pH, initially around 13, falls to values where carbonate ion is the most dominant element (pH ~ 9), then CaCO3 phases can precipitate. These studies mainly associate carbonation process with a reduction of porosity and permeability. Indeed an increase of volume (about 10%) is expected during the formation of calcite from portlandite assuming a stoichiometric reaction. Here we investigated the cement alteration mechanisms in the frame of a controlled continuous renewal of CO2-rich fluid in a fracture. This situation is that expected when seepage is activated by the mechanical failure of the cement material that initially seals two layers of distinctly different pressure: the storage reservoir and the aquifer above the caprock, for instance. We study the effect of flow rates from quasi-static flow to higher flow rates for well-connected fractures. In the quasi-static case we observed an extensive conversion of portlandite (Ca(OH)2) to calcite in the vicinity of the fracture similar to that observed in the published batch experiments. Eventually, the fracture was almost totally healed. The experiments with constant flow revealed a different behavior triggered by the continuous renewing of the reactants and withdrawal of the reaction products. We showed that calcite precipitation is more efficient for low flow rate. With intermediate flow rate, we measured that permeability increases slowly at the beginning of the experiment and then remains constant due to calcite precipitation in replacement of CSH and CH into fracture border. With higher flow rate, we measured a constant permeability which can be explained by the development of a highly hydrated Si-rich zone which maintains the initial fracture aperture during all over the experiment while noticeable mass is released from the sample. These results emphasize that more complex behaviors than that envisaged from batch experiments may take place in the vicinity of flowing fractures. We demonstrated that if only micro-cracks appear in the cement well, carbonation reaction may heal these micro-cracks and mitigate leakage whereas conductive fractures allowing high flow may represent a risk of perennial leakage because the net carbonation process, including the calcite precipitation and its subsequent re-dissolution, is sufficiently to heal the fracture. However, the precipitation of Si-rich amorphous phases may maintain the initial fracture aperture and limit the leakage rate.

Oral Solid Dosage Form Disintegration Testing - The Forgotten Test.

PubMed

Al-Gousous, Jozef; Langguth, Peter

2015-09-01

Since its inception in the 1930s, disintegration testing has become an important quality control (QC) test in pharmaceutical industry, and disintegration test procedures for various dosage forms have been described by the different pharmacopoeias, with harmonization among them still not quite complete. However, because of the fact that complete disintegration does not necessarily imply complete dissolution, much more research has been focused on dissolution rather than on disintegration testing. Nevertheless, owing to its simplicity, disintegration testing seems to be an attractive replacement to dissolution testing as recognized by the International Conference on Harmonization guidelines, in some cases. Therefore, with proper research being carried out to overcome the associated challenges, the full potential of disintegration testing could be tapped saving considerable efforts allocated to QC testing and quality assurance. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

Integrating In Vitro, Modeling, and In Vivo Approaches to Investigate Warfarin Bioequivalence

PubMed Central

Wen, H; Fan, J; Vince, B; Li, T; Gao, W; Kinjo, M; Brown, J; Sun, W; Jiang, W; Lionberger, R

2017-01-01

We demonstrate the use of modeling and simulation to investigate bioequivalence (BE) concerns raised about generic warfarin products. To test the hypothesis that the loss of isopropyl alcohol and slow dissolution in acidic pH has significant impact on the pharmacokinetics of warfarin sodium tablets, we conducted physiologically based pharmacokinetic absorption modeling and simulation using formulation factors or in vitro dissolution profiles as input parameters. Sensitivity analyses indicated that warfarin pharmacokinetics was not sensitive to solubility, particle size, density, or dissolution rate in pH 4.5, but was affected by dissolution rate in pH 6.8 and potency. Virtual BE studies suggested that stressed warfarin sodium tablets with slow dissolution rate in pH 4.5 but having similar dissolution rate in pH 6.8 would be bioequivalent to the unstressed warfarin sodium tablets. A four‐way, crossover, single‐dose BE study in healthy subjects was conducted to test the same hypothesis and confirmed the simulation conclusion. PMID:28379643

Designing a dynamic dissolution method: a review of instrumental options and corresponding physiology of stomach and small intestine.

PubMed

Culen, Martin; Rezacova, Anna; Jampilek, Josef; Dohnal, Jiri

2013-09-01

Development of new pharmaceutical compounds and dosage forms often requires in vitro dissolution testing with the closest similarity to the human gastrointestinal (GI) tract. To create such conditions, one needs a suitable dissolution apparatus and the appropriate data on the human GI physiology. This review discusses technological approaches applicable in biorelevant dissolutions as well as the physiology of stomach and small intestine in both fasted and fed state, that is, volumes of contents, transit times for water/food and various solid oral dosage forms, pH, osmolality, surface tension, buffer capacity, and concentrations of bile salts, phospholipids, enzymes, and Ca(2+) ions. The information is aimed to provide clear suggestions on how these conditions should be set in a dynamic biorelevant dissolution test. Copyright © 2013 Wiley Periodicals, Inc.

Use of bicarbonate buffer systems for dissolution characterization of enteric-coated proton pump inhibitor tablets.

PubMed

Shibata, Hiroko; Yoshida, Hiroyuki; Izutsu, Ken-Ichi; Goda, Yukihiro

2016-04-01

The aim of this study was to assess the effects of buffer systems (bicarbonate or phosphate at different concentrations) on the in vitro dissolution profiles of commercially available enteric-coated tablets. In vitro dissolution tests were conducted using an USP apparatus II on 12 enteric-coated omeprazole and rabeprazole tablets, including innovator and generic formulations in phosphate buffers, bicarbonate buffers and a media modified Hanks (mHanks) buffer. Both omeprazole and rabeprazole tablets showed similar dissolution profiles among products in the compendial phosphate buffer system. However, there were large differences between products in dissolution lag time in mHanks buffer and bicarbonate buffers. All formulations showed longer dissolution lag times at lower concentrations of bicarbonate or phosphate buffers. The dissolution rank order of each formulation differed between mHanks buffer and bicarbonate buffers. A rabeprazole formulation coated with a methacrylic acid copolymer showed the shortest lag time in the high concentration bicarbonate buffer, suggesting varied responses depending on the coating layer and buffer components. Use of multiple dissolution media during in vitro testing, including high concentration bicarbonate buffer, would contribute to the efficient design of enteric-coated drug formulations. © 2016 Royal Pharmaceutical Society, Journal of Pharmacy and Pharmacology.

[Evaluation of Dissolution Profiles of Famotidine from Over-the-counter Drugs].

PubMed

Saito, Yuji; Adachi, Naoki; Kato, Miki; Nadai, Masayuki

2018-03-27

  In recent years, self-medication has started to receive more attention in Japan owing to increasing medical costs and health awareness among people. One of the main roles of pharmacists in self-medication is to provide appropriate information regarding over-the-counter (OTC) drugs. However, pharmacists promoting the proper use of OTC drugs have little information on their formulation properties. In this study, we performed dissolution tests on both OTC drugs and ethical drug (ED) containing famotidine, and evaluated the differences in their dissolution profiles. Marked differences in dissolution profiles of OTC drugs were observed in test solutions at pH 1.2, 4.0, and 6.8 and in water. To evaluate the differences quantitatively, we calculated the lag time and dissolution rate constant from the dissolution profiles. Significant differences in lag times and dissolution rate constants between some OTC drugs and ED were observed. We also used similarity factor (f2), to quantify the similarity between dissolution profiles of OTC drugs and ED. f2 values less than 42 were observed in some OTC drugs, suggesting that these differences might influence absorption in vivo resulting in differences in their onset time and efficacy. The findings of this study will provide useful information for the promotion of proper use of OTC drugs.

[Comparison in dissolution behavior of ethical and over-the counter scopolamine butylbromide].

PubMed

Suzuki, Ichie; Miyazaki, Yasunori; Uchino, Tomonobu; Kagawa, Yoshiyuki

2011-01-01

Marketing authorization holders do not disclose any information on the pharmaceutical properties of over-the-counter drugs (OTC). When a drug is switched from a prescription drug to OTC, pharmacists can acquire that information from the corresponding ethical drug (ED) through the package insert, interview form, and so on. However, the pharmaceutical equivalence between ED and OTC is unclear. In this study, we examined the drug dissolution behavior of both ED and OTCs containing scopolamine butylbromide. Dissolution tests were performed by the paddle method using Japanese Pharmacopeia (JP) XV test fluids at pH 1.2, 4.0 and 6.8 and water based on the guidelines for bioequivalence studies of generic products. The dissolution profiles of OTCs differed significantly from ED showing a similarity factor (f2) value ranging from 8.9 to 42.9. Time until 85% dissolution ranged from 23 to 95 min and from 17 to 174 min at pH 1.2 and pH 6.8, respectively. Then JP XV disintegration tests were conducted to investigate differences in the disintegration process. The disintegration time of preparations showing delayed dissolution was prolonged compared to that of others, suggesting that the disintegration of the tablet or capsule is one of the important factors affecting the drug dissolution. These differences in the disintegration and drug dissolution might cause differences in the bioavailability of the drug. For patient safety, more detailed product information of OTCs should be supplied by the manufacturer, and not be assumed from that of corresponding ED.

Mineral displacement and -dissolution processes and their relevance to rock porosity and permeability in Rotliegend sandstones of the Altmark natural gas field (central Germany) - results from CO2 laboratory batch experiments

NASA Astrophysics Data System (ADS)

Pudlo, Dieter; Enzmann, Frieder; Heister, Katja; Werner, Lars; Ganzer, Leonhard; Reitenbach, Viktor; Henkel, Steven; Albrecht, Daniel; Gaupp, Reinhard

2014-05-01

The Rotliegend reservoir sandstones of the Altmark area (central Germany) comprise the second largest natural gas field of Europe. These sandstones were deposited on a playa-like continental platform with braided river systems, ephemeral lakes and aeolian dunes under semi-arid conditions. Some of the pristine, red coloured deposits suffered intensive late diagenetic alteration and are now preserved as bleached, high porous and permeable sandstones. To evaluate the relevance of distinct fluids and their fluid-rock alteration reactions on such bleaching processes we performed laboratory static batch experiments on the Altmark sandstones. These 4-6 week lasting runs were conducted with CO2 saturated synthetic brines under typical Altmark reservoir conditions (p= 20 MPa, T= 125°C). Thereby mineralogical, petrophysical and (hydro- and geo-) chemical rock features were maintained prior and after the experiments. Chemical data proved the dissolution of carbonate and sulphate minerals during the runs, whereas the variation in abundance of further elements was within the detection limit of analytical accuracy. However, FE-SEM investigations on used, evaporated brines reveal the presence of illite and chlorite minerals within a matrix of Ca-, Si-, Fe, Al-, Na- and S components (carbonate, anhydrite, albite and Fe-(hydr-) oxides ?). By porosity and relative permeability measurements an increase in both rock features was observed after the runs, indicating that mineral dissolution and/or (clay) fine migration/detachment occurred during the experiments. Mineral dissolution, especially of pore-filling cements (e.g. carbonate-, sulphate minerals) is also deduced by BET analysis, in determining the specific surface of the sandstones. The size of these reactive surfaces increased after the experiments, suggesting that after the dissolution of pore-filling cements, formerly armoured grain rimming clay cutans were exposed to potential migrating fluids. These findings are also supported by µ-CT investigations. Here, the achieved 3D modelling data indicate an increase in reactive surface areas exposed to the pore space (which is in accord to the BET observations), as well as an enhancement in rock porosity and permeability after the runs. Moreover, these simulations showed that a remarkable mass (mineral) transfer was induced by the experiments, which led to a displacement of the porosity and permeability distribution in the sandstones and therefore a change in the fluid flow characteristics within the rocks - a parameter most important for every fluid-rock process. These observations are quite astonishing because they suggest that not only fluid velocity (e.g. during fluid flow experiments) might detach and transport grain rimming (clay) minerals, but also that physico-chemical reactions may enforce the release of such solids, even during almost static p-/T-/Xfluid conditions, as used in our experiments.

[Troubleshooting of bioinequivalence of compound valsartan tablets].

PubMed

Shao, Da; Zhang, Yi-Fan; Zhan, Yan; Chen, Xiao-Yan; Zhong, Da-Fang

2014-04-01

The study aims to evaluate the bioequivalence of valsartan hydrochlorothiazide tablets, and to investigate the potential cause of bioinequivalence. This was a single-center study with an open, randomized double-way crossover design. Test and reference preparations containing 160 mg of valsartan and 25 mg of hydrochlorothiazide were given to 36 healthy male volunteers. Plasma concentrations of valsartan and hydrochlorothiazide were determined simultaneously by LC-MS/MS. The pharmacokinetic parameters and relative bioavailability were calculated, while the bioequivalence between test and reference preparations were evaluated. The dissolution profiles of test and reference preparations in four different mediums were determined via dissolution test and HPLC. The similarity was investigated according to the similarity factors (f2). The F(o-t) and F(0-infinity) were (139.4 +/- 65.2)% and (137.5 +/- 61.2)% for valsartan of test preparations. It led to get the conclusion that test and reference preparations were not bioequivalent for valsartan. A significant difference was observed between test and reference tablets in the valsartan dissolution test of pH 1.2 hydrochloric acid solution. The key factor of the bioinequivalence might be that dissolution of valsartan in acid medium has marked difference between two preparations.

Novel biorelevant dissolution medium as a prognostic tool for polysaccharide-based colon-targeted drug delivery system.

PubMed

Yadav, Ankit Kumar; Sadora, Manik; Singh, Sachin Kumar; Gulati, Monica; Maharshi, Peddi; Sharma, Abhinav; Kumar, Bimlesh; Rathee, Harish; Ghai, Deepak; Malik, Adil Hussain; Garg, Varun; Gowthamrajan, K

2017-01-01

To overcome the limitations of the conventionally used methods for evaluation of orally administered colon-targeted delivery systems, a novel dissolution method using probiotics has been recently reported. In the present study, universal suitability of this medium composed of five different probiotics is established. Different delivery systems - mini tablets, liquisolid compacts, and microspheres coated with different polysaccharides - were prepared and subjected to sequential dissolution testing in medium with and without microbiota. The results obtained from fluid thioglycollate medium (FTM)-based probiotic medium for all the polysaccharide-based formulations showed statistically similar dissolution profile to that in the rat and goat cecal content media. Hence, it can be concluded that the developed FTM-based probiotic medium, once established, may eliminate the need for further animal sacrifice in the dissolution testing of polysaccharide-based colon-targeted delivery system.

Development and validation of a discriminative dissolution method for atorvastatin calcium tablets using in vivo data by LC and UV methods.

PubMed

Machado, J C; Lange, A D; Todeschini, V; Volpato, N M

2014-02-01

A dissolution method to analyze atorvastatin tablets using in vivo data for RP and test pilot (PB) was developed and validated. The appropriate conditions were determined after solubility tests using different media, and sink conditions were established. The conditions used were equipment paddle at 50 rpm and 900 mL of potassium phosphate buffer pH 6.0 as dissolution medium. In vivo release profiles were obtained from the bioequivalence study of RP and the generic candidate PB. The fraction of dose absorbed was calculated using the Loo-Riegelman method. It was necessary to use a scale factor of time similar to 6.0, to associate the values of absorbed fraction and dissolved fraction, obtaining an in vivo-in vitro correlation level A. The dissolution method to quantify the amount of drug dissolved was validated using high-performance liquid chromatography and ultraviolet spectrophotometry, and validated according to the USP protocol. The discriminative power of dissolution conditions was assessed using two different pilot batches of atorvastatin tablets (PA and PB) and RP. The dissolution test was validated and may be used as a discriminating method in quality control and in the development of the new formulations.

Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS): A rapid test for enteric coating thickness and integrity of controlled release pellet formulations.

PubMed

Alfarsi, Anas; Dillon, Amy; McSweeney, Seán; Krüse, Jacob; Griffin, Brendan; Devine, Ken; Sherry, Patricia; Henken, Stephan; Fitzpatrick, Stephen; Fitzpatrick, Dara

2018-06-10

There are no rapid dissolution based tests for determining coating thickness, integrity and drug concentration in controlled release pellets either during production or post-production. The manufacture of pellets requires several coating steps depending on the formulation. The sub-coating and enteric coating steps typically take up to six hours each followed by additional drying steps. Post production regulatory dissolution testing also takes up to six hours to determine if the batch can be released for commercial sale. The thickness of the enteric coating is a key factor that determines the release rate of the drug in the gastro-intestinal tract. Also, the amount of drug per unit mass decreases with increasing thickness of the enteric coating. In this study, the coating process is tracked from start to finish on an hourly basis by taking samples of pellets during production and testing those using BARDS (Broadband Acoustic Resonance Dissolution Spectroscopy). BARDS offers a rapid approach to characterising enteric coatings with measurements based on reproducible changes in the compressibility of a solvent due to the evolution of air during dissolution. This is monitored acoustically via associated changes in the frequency of induced acoustic resonances. A steady state acoustic lag time is associated with the disintegration of the enteric coatings in basic solution. This lag time is pH dependent and is indicative of the rate at which the coating layer dissolves. BARDS represents a possible future surrogate test for conventional USP dissolution testing as its data correlates directly with the thickness of the enteric coating, its integrity and also with the drug loading as validated by HPLC. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of formulation additives on in vitro dissolution-absorption profile and in vivo bioavailability of telmisartan from brand and generic formulations.

PubMed

Borbás, Enikő; Nagy, Zsombor K; Nagy, Brigitta; Balogh, Attila; Farkas, Balázs; Tsinman, Oksana; Tsinman, Konstantin; Sinkó, Bálint

2018-03-01

In this study, brand and four generic formulations of telmisartan, an antihypertensive drug, were used in in vitro simultaneous dissolution-absorption, investigating the effect of different formulation additives on dissolution and on absorption through an artificial membrane. The in vitro test was found to be sensitive enough to show even small differences between brand and generic formulations caused by the use of different excipients. By only changing the type of filler from sorbitol to mannitol in the formulation, the flux through the membrane was reduced by approximately 10%. Changing the salt forming agent as well resulted in approximately 20% of flux reduction compared to the brand formulation. This significant difference was clearly shown in the published in vivo results as well. The use of additional lactose monohydrate in the formulation also leads to approximately 10% reduction in flux. The results show that by changing excipients, the dissolution of telmisartan was not altered significantly, but the flux through the membrane was found to be significantly changed. These results pointed out the limitations of traditional USP dissolution tests and emphasized the importance of simultaneously measuring dissolution and absorption, which allows the complex effect of formulation excipients on both processes to be measured. Moreover, the in vivo predictive power of the simultaneous dissolution-absorption test was demonstrated by comparing the in vitro fluxes to in vivo bioequivalence study results. Copyright © 2018 Elsevier B.V. All rights reserved.

The effect of 8.25% sodium hypochlorite on dental pulp dissolution and dentin flexural strength and modulus.

PubMed

Cullen, James K T; Wealleans, James A; Kirkpatrick, Timothy C; Yaccino, John M

2015-06-01

The purpose of this study was to evaluate the effect of various concentrations of sodium hypochlorite (NaOCl), including 8.25%, on dental pulp dissolution and dentin flexural strength and modulus. Sixty dental pulp samples and 55 plane parallel dentin bars were retrieved from extracted human teeth. Five test groups (n = 10) were formed consisting of a pulp sample and dentin bar immersed in various NaOCl solutions. The negative control group (n = 5) consisted of pulp samples and dentin bars immersed in saline. The positive control group (n = 5) consisted of pulp samples immersed in 8.25% NaOCl without a dentin bar. Every 6 minutes for 1 hour, the solutions were refreshed. The dentin bars were tested for flexural strength and modulus with a 3-point bend test. The time until total pulp dissolution and any changes in dentin bar flexural strength and modulus for the different NaOCl solutions were statistically analyzed. An increase in NaOCl concentration showed a highly significant decrease in pulp dissolution time. The pulp dissolution property of 8.25% NaOCl was significantly faster than any other tested concentration of NaOCl. The presence of dentin did not have a significant effect on the dissolution capacity of NaOCl if the solutions were refreshed. NaOCl concentration did not have a statistically significant effect on dentin flexural strength or modulus. Dilution of NaOCl decreases its pulp dissolution capacity. Refreshing the solution is essential to counteract the effects of dentin. In this study, NaOCl did not have a significant effect on dentin flexural strength or modulus. Published by Elsevier Inc.

Development of a biphasic dissolution test for Deferasirox dispersible tablets and its application in establishing an in vitro-in vivo correlation.

PubMed

Al Durdunji, Amal; AlKhatib, Hatim S; Al-Ghazawi, Mutasim

2016-05-01

In a biphasic dissolution medium, the integration of the in vitro dissolution of a drug in an aqueous phase and its subsequent partitioning into an organic phase is hypothesized to simulate the in vivo drug absorption. Such a methodology is expected to improve the probability of achieving a successful in vitro-in vivo correlation. Dissolution of Dispersible tablets of Deferasirox, a biopharmaceutics classification system type II compound, was studied in a biphasic dissolution medium using a flow-through dissolution apparatus coupled to a paddle apparatus. The experimental parameters associated with dissolution were optimized to discriminate between Deferasirox dispersible tablets of different formulations. The dissolution profiles obtained from this system were subsequently used to construct a level A in vitro-in vivo correlation. Copyright © 2016 Elsevier B.V. All rights reserved.

Tissue dissolution by a novel multisonic ultracleaning system and sodium hypochlorite.

PubMed

Haapasalo, Markus; Wang, Zhejun; Shen, Ya; Curtis, Allison; Patel, Payal; Khakpour, Mehrzad

2014-08-01

This study aimed to evaluate the effectiveness of a novel Multisonic Ultracleaning System (Sonendo Inc, Laguna Hills, CA) in tissue dissolution in comparison with conventional irrigation devices. Pieces of bovine muscle tissue (68 ± 2 mg) were placed in 0.7-mL test tubes (height: 23.60 mm, inner diameter: 6.00 mm, outer diameter: 7.75 mm) and exposed to 5 minutes of irrigation by different devices. Endodontic devices included the Multisonic Ultracleaning System, the Piezon Master 700 (EMS, Dallas, TX) ultrasonic system with agitation, the EndoVac negative-pressure irrigation system (SybronEndo, Orange, CA), and a conventional positive-pressure 27-G irrigation needle at a flow rate of 10 mL/min. The systems were tested with 0.5%, 3%, and 6% sodium hypochlorite (NaOCl) at room temperature (21°C) as well as 40°C. Irrigation with sterile water was used as a control. The mass of tissue specimens was measured and recorded before and after the use of each device, and if the specimen was completely dissolved visually within 5 minutes, the dissolution time was recorded. The rate of tissue dissolution (%/s) was then calculated. The Multisonic Ultracleaning System had the fastest rate of tissue dissolution (P < .05), at 1.0% ± 0.1% per second using 0.5% NaOCl, 2.3% ± 0.9% per second using 3% NaOCl, and 2.9% ± 0.7% per second using 6% NaOCl. This tissue dissolution rate was more than 8 times greater than the second fastest device tested (P < .01), the Piezon Master 700 ultrasonic system, which resulted in a tissue dissolution rate of 0.328% ± 0.002% per second using 6% NaOCl at 40°C. For all irrigation devices tested, the rate of tissue dissolution increased with a higher concentration and temperature of the NaOCl solution. The novel Multisonic Ultracleaning System achieved a significantly faster tissue dissolution rate when compared with the other systems examined in vitro. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Formulation Predictive Dissolution (fPD) Testing to Advance Oral Drug Product Development: an Introduction to the US FDA Funded '21st Century BA/BE' Project.

PubMed

Hens, Bart; Sinko, Patrick; Job, Nicholas; Dean, Meagan; Al-Gousous, Jozef; Salehi, Niloufar; Ziff, Robert M; Tsume, Yasuhiro; Bermejo, Marival; Paixão, Paulo; Brasseur, James G; Yu, Alex; Talattof, Arjang; Benninghoff, Gail; Langguth, Peter; Lennernäs, Hans; Hasler, William L; Marciani, Luca; Dickens, Joseph; Shedden, Kerby; Sun, Duxin; Amidon, Gregory E; Amidon, Gordon L

2018-06-23

Over the past decade, formulation predictive dissolution (fPD) testing has gained increasing attention. Another mindset is pushed forward where scientists in our field are more confident to explore the in vivo behavior of an oral drug product by performing predictive in vitro dissolution studies. Similarly, there is an increasing interest in the application of modern computational fluid dynamics (CFD) frameworks and high-performance computing platforms to study the local processes underlying absorption within the gastrointestinal (GI) tract. In that way, CFD and computing platforms both can inform future PBPK-based in silico frameworks and determine the GI-motility-driven hydrodynamic impacts that should be incorporated into in vitro dissolution methods for in vivo relevance. Current compendial dissolution methods are not always reliable to predict the in vivo behavior, especially not for biopharmaceutics classification system (BCS) class 2/4 compounds suffering from a low aqueous solubility. Developing a predictive dissolution test will be more reliable, cost-effective and less time-consuming as long as the predictive power of the test is sufficiently strong. There is a need to develop a biorelevant, predictive dissolution method that can be applied by pharmaceutical drug companies to facilitate marketing access for generic and novel drug products. In 2014, Prof. Gordon L. Amidon and his team initiated a far-ranging research program designed to integrate (1) in vivo studies in humans in order to further improve the understanding of the intraluminal processing of oral dosage forms and dissolved drug along the gastrointestinal (GI) tract, (2) advancement of in vitro methodologies that incorporates higher levels of in vivo relevance and (3) computational experiments to study the local processes underlying dissolution, transport and absorption within the intestines performed with a new unique CFD based framework. Of particular importance is revealing the physiological variables determining the variability in in vivo dissolution and GI absorption from person to person in order to address (potential) in vivo BE failures. This paper provides an introduction to this multidisciplinary project, informs the reader about current achievements and outlines future directions. Copyright © 2018. Published by Elsevier B.V.

Silicon Isotopes doping experiments to measure quartz dissolution and precipitation rates at equilibrium and test the principle of detailed balance

NASA Astrophysics Data System (ADS)

Zhu, C.; Rimstidt, J. D.; Liu, Z.; Yuan, H.

2016-12-01

The principle of detailed balance (PDB) has been a cornerstone for irreversible thermodynamics and chemical kinetics for a long time, and its wide application in geochemistry has mostly been implicit and without experimental testing of its applicability. Nevertheless, many extrapolations based on PDB without experimental validation have far reaching impacts on society's mega environmental enterprises. Here we report an isotope doping method that independently measures simultaneous dissolution and precipitation rates and can test this principle. The technique reacts a solution enriched in a rare isotope of an element with a solid having natural isotopic abundances (Beck et al., 1992; Gaillardet, 2008; Gruber et al., 2013). Dissolution and precipitation rates are found from the changing isotopic ratios. Our quartz experiment doped with 29Si showed that the equilibrium dissolution rate remains unchanged at all degrees of undersaturation. We recommend this approach to test the validity of using the detailed balance relationship in rate equations for other substances.

The influence of co-formers on the dissolution rates of co-amorphous sulfamerazine/excipient systems.

PubMed

Gniado, Katarzyna; Löbmann, Korbinian; Rades, Thomas; Erxleben, Andrea

2016-05-17

A comprehensive study on the dissolution properties of three co-amorphous sulfamerazine/excipient systems, namely sulfamerazine/deoxycholic acid, sulfamerazine/citric acid and sulfamerazine/sodium taurocholate (SMZ/DA, SMZ/CA and SMZ/NaTC; 1:1 molar ratio), is reported. While all three co-formers stabilize the amorphous state during storage, only co-amorphization with NaTC provides a dissolution advantage over crystalline SMZ and the reasons for this were analyzed. In the case of SMZ/DA extensive gelation of DA protects the amorphous phase from crystallization upon contact with buffer, but at the same time prevents the release of SMZ into solution. Disk dissolution studies showed an improved dissolution behavior of SMZ/CA compared to crystalline SMZ. However, enhanced dissolution properties were not seen in powder dissolution testing due to poor dispersibility. Co-amorphization of SMZ and NaTC resulted in a significant increase in dissolution rate, both in powder and disk dissolution studies. Copyright © 2016. Published by Elsevier B.V.

Testing lyoequivalency for three commercially sustained-release tablets containing diltiazem hydrochloride.

PubMed

Maswadeh, Hamzah A; Al-Hanbali, Othman A; Kanaan, Reem A; Shakya, Ashok K; Maraqa, Anwar

2010-01-01

In vitro release kinetics of three commercially available sustained release tablets (SR) diltiazem hydrochloride were studied at pH 1.1 for 2 h and for another 6 h at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process was studied by analyzing the dissolution data using five kinetic equations: the zero-order equation, the first-order equation, the Higuchi square root equation, the Hixson-Crowell cube root law and the Peppas equation. Analyses of the dissolution kinetic data for diltiazem hydrochloride commercial SR tablets showed that both Dilzacard and Dilzem SR tablets released drug by Non-Fickian (Anomalous transport) release with release exponent (n) equal to 0.59 and 0.54, respectively, which indicate the summation of both diffusion and dissolution controlled drug release. Bi-Tildiem SR tablets released drug by super case II (n = 1.29) which indicate zero-order release due to the dissolution of polymeric matrix and relaxation of the polymer chain. This finding was also in agreement with results obtained from application of zero-order and Hixson-Crowell equations. A dissolution profile comparative study was done to test the lyoequivelancy of the three products by using the mean dissolution time (MDT), dissimilarity factor f1 and similarity factor f2. Results showed that the three products are different and not lyoequivalent.

75 FR 8081 - Patrick J. Lais: Debarment Order

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-23

..., among other things, subpotent burn spray, aspirin that had failed dissolution testing, and antacid... as ``Uncoated Aspirin.'' This drug failed its final dissolution testing. Neither Mr. Lais nor the... coated the failed aspirin and renumbered the lot. Part of this lot then was packaged as ``Coated Aspirin...

Addition of Sodium Bicarbonate to Irrigation Solution May Assist in Dissolution of Uric Acid Fragments During Ureteroscopy.

PubMed

Paonessa, Jessica E; Williams, James C; Lingeman, James E

2018-04-01

We hypothesized that adding sodium bicarbonate (bicarb) to normal saline (NS) irrigation during ureteroscopy in patients with uric acid (UA) nephrolithiasis may assist in dissolving small stone fragments produced during laser lithotripsy. In vitro testing was performed to determine whether dissolution of UA fragments could be accomplished within 1 hour. In total 100% UA renal calculi were fragmented, filtered, and separated by size. Fragment sizes were <0.5 mm and 0.5 to 1 mm. Similar amounts of stone material were agitated in solution at room temperature. Four solutions were tested (NS, NS +1 ampule bicarb/L, NS +2, NS +3). Both groups were filtered to remove solutions after fixed periods. Filtered specimens were dried and weighed. Fragment dissolution rates were calculated as percent removed per hour. Additional testing was performed to determine whether increasing the temperature of solution affected dissolution rates. For fragments <0.5 mm, adding 2 or 3 bicarb ampules/L NS produced a dissolution rate averaging 91% ± 29% per hour. This rate averaged 226% faster than NS alone. With fragments 0.5 to 1 mm, addition of 2 or 3 bicarb ampules/L NS yielded a dissolution rate averaging 22% ± 7% per hour, which was nearly five times higher than NS alone. There was a trend for an increase in mean dissolution rate with higher temperature but this increase was not significant (p = 0.30). The addition of bicarbonate to NS more than doubles the dissolution rate of UA stone fragments and fragments less than 0.5 mm can be completely dissolved within 1 hour. Addition of bicarb to NS irrigation is a simple and inexpensive approach that may assist in the dissolution of UA fragments produced during ureteroscopic laser lithotripsy. Further studies are needed to determine whether a clinical benefit exists.

Investigation of the Dissolution Profile of Gliclazide Modified-Release Tablets Using Different Apparatuses and Dissolution Conditions.

PubMed

Skripnik, K K S; Riekes, M K; Pezzini, B R; Cardoso, S G; Stulzer, H K

2017-07-01

In the absence of an official dissolution method for modified-release tablets of gliclazide, dissolution parameters, such as apparatuses (1, 2, and 3), rotation speeds, pH, and composition of the dissolution medium were investigated. The results show that although the drug presents a pH-mediated solubility (pH 7.0 > 6.8 > 6.4 > 6.0 > 5.5 > 4.5), the in vitro release of the studied tablets was not dependent on this parameter, despite of the apparatus tested. On the other hand, the rotation speed demonstrated a greater influence (100 rpm >50 rpm). Using similar hydrodynamic conditions, the three different apparatuses were compared in pH 6.8 and provided the following trend: apparatus 1 at 100 rpm >2 at 50 rpm ≈3 at 10 dpm. As a complete, but slow release is expected from modified-release formulations, apparatus 2, in phosphate buffer pH 6.8 and 100 rpm, were selected as the optimized dissolution method. In comparison to apparatus 1 under the same conditions, the paddle avoids the stickiness of formulation excipients at the mesh of the basket, which could prejudice the release of gliclazide. Results obtained with biorelevant medium through the developed dissolution method were similar to the buffer solution pH 6.8. The application of the optimized method as a quality control test between two different brands of gliclazide modified-release tablets showed that both dissolution profiles were considered similar by the similarity factor (f2 = 51.8). The investigation of these dissolution profiles indicated a dissolution kinetic following first-order model.

Experimental study on corrosion and precipitation in non-isothermal Pb-17Li system for development of liquid breeder blanket of fusion reactor

NASA Astrophysics Data System (ADS)

Kondo, Masatoshi; Ishii, Masaomi; Norimatsu, Takayoshi; Muroga, Takeo

2017-07-01

The corrosion characteristics of RAFM steel JLF-1 in a non-isothermal Pb-17Li flowing system were investigated by means of the corrosion test using a non-isothermal mixing pot. The corrosion test was performed at 739K with a temperature gradient of 14K for 500 hours. The corrosion tests at a static and a flowing conditions in an isothermal Pb-17Li system were also performed at the same temperature for the same duration with the non-isothermal test. Then, the effect of mass transfer both by the flow and the temperature gradient on the corrosion behaviors was featured by the comparison of these results. The corrosion was caused by the dissolution of Fe and Cr from the steel surface into the flowing Pb-17Li. The specimen surface revealed a fine granular microstructure after the corrosion tests. A large number of pebbleshaped protrusions were observed on the specimen surface. This microstructure was different from the original martensite microstructure of the steel, and might be formed by the influence of the reaction with Li component in the alloy. The formation of the granular microstructure was accelerated by the flow and the temperature gradient. Some pebble-shaped protrusions had gaps at their bases. The removal of these pebble-shaped granules by the flowing Pb-17Li might cause a small-scale corrosion-erosion. The results of metallurgical analysis indicated that a large-scale corrosion-erosion was also caused by their destruction of the corroded layer on the surface. The non-isothermal mixing pot equipped a cold trap by a metal mesh in the low temperature region. The metal elements of Fe and Cr were recovered as they precipitated on the surface of the metal mesh. It was found that a Fe-Cr binary intermetallic compound was formed in the precipitation procedure. The overall mass transfer coefficient for the dissolution type corrosion in the non-isothermal system was much bigger than that in the isothermal system. This model evaluation indicated that the temperature gradient accelerated the corrosion.

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

PubMed

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

Preventing Small Molecule Nucleation and Crystallization by Sequestering in a Micelle Corona

NASA Astrophysics Data System (ADS)

Li, Ziang; Johnson, Lindsay; Ricarte, Ralm; Yao, Letitia; Hillmyer, Marc; Bates, Frank; Lodge, Timothy

We exploited a blend of hydroxypropyl methylcellulose acetate succinate and poly(N-isopropylacrylamide) (PNIPAm) to improve the solubility and dissolution of a rapidly crystallizing model drug molecule phenytoin and observed synergistic effect in vitro at constant drug loading by varying the blending ratio. Dynamic and static light scattering experiments showed that PNIPAm self-assembled into micelles in aqueous solution. We believe that adding these PNIPAm micelles inhibited both nucleation and crystal growth of phenytoin based on the polarized light micrographs taken from the dissolution media. The drug-polymer intermolecular interaction was revealed by nuclear Overhauser effect spectroscopy and further quantified by diffusion ordered spectroscopy. We found that the phenytoin molecules were sequestered in aqueous solution by partitioning into the corona of the micelle. The blend strategy through the use of self-assembled micelles showcased in this study offers a new platform for designing advanced excipients for oral drug delivery. This study was funded by The Dow Chemical Company through Agreement 224249AT with the University of Minnesota.

Effects of Temperature and Method of Solution Preparation on the Performance of a Typical Red Mud Flocculent

NASA Astrophysics Data System (ADS)

Ferland, Pierre; Malito, John T.; Phillips, Everett C.

Alcan International Ltd. in collaboration with Ondeo Nalco Company have carried out a fundamental study on the dissolution and performance of a 100% anionic polymer. The effects of method of preparation, solvent composition, temperature and exposure time on flocculent activity under conditions relevant to both atmospheric and pressure decantation were investigated. Flocculent activity was determined using static and dynamic settling tests, and the results were correlated with the reduced specific viscosity (RSV). For any given method of preparation of the flocculent solutions (makeup/dilution) the RSV tended to decrease with increasing solution ionic strength, independent of ionic speciation. While a significant loss in flocculent activity occurred with long exposure of the solution to high temperature, only a minor loss occurred in the short time required to flocculate and settle the mud in a decanter operating at 150 °C. Recent results in an actual plant pressure decanter appear to validate this conclusion.

The effects of redox fluctuation on iron-organic matter interactions in wet tropical soils

NASA Astrophysics Data System (ADS)

Bhattacharyya, A.; Campbell, A.; Lin, Y.; Nico, P. S.; Silver, W. L.; Pett-Ridge, J.

2016-12-01

Two-thirds of the C in the terrestrial biosphere is stored as soil organic C, and much of this is stabilized via iron (Fe) mineral-organic matter (OM) associations that are susceptible to redox effects. The rapid C cycling typical of wet tropical ecosystems- driven by ample moisture and temperature- may also be fueled by a characteristically dynamic redox environment. Yet the net result of altered tropical soil climate and fluctuating soil redox regimes on Fe-organic matter associations is poorly understood. In this study, we hypothesized that the timing of redox transitions (frequency of O2 introduction and ferrous iron (Fe2+) generation) will lead to differences in Fe (oxyhydr)oxide mineral crystallinity and C degradation rates and alter the proportion of organic C associated with iron minerals. Surface soils from a humid tropical forest in Puerto Rico were incubated for 44 days under four redox regimes: (1) static anoxic, (2) static oxic, (3) 4 days anoxic, 4 days oxic, and (4) 4 days anoxic, 8 days oxic. Replicate microcosms were harvested at multiple time points, including before and after a redox switch (oxic to anoxic or vice versa). Selective chemical extractions, bulk Fe K-edge EXAFS and STXM/NEXAFS spectromicroscopy were used to comprehensively probe treatment effects on Fe and C speciation. Static redox conditions had a significant effect on Fe2+ and dissolved organic carbon (DOC) concentrations, and prolonged anoxia promoted reductive dissolution of Fe-oxides and an increase in amorphous or short-range ordered (SRO) Fe oxides. Preferential dissolution of this less-crystalline Fe pool was more prominent during rapid redox switches from oxic to anoxic conditions, and coincided with increased DOC. Bulk Fe K-edge EXAFS spectroscopy identified Fe3+ as the dominant Fe species in all treatments and indicated O/N atoms in the first Fe co-ordination sphere and features similar to SRO Fe-oxide phases (e.g. ferrihydrite or nano-goethite) in the second co-ordination sphere. STXM/NEXAFS analyses indicated an increase in lignin-like biomolecules under static anoxic conditions, and a potential role of Fe-lignin interactions under strong reducing conditions. Our current findings highlight the necessity to explore natural redox-dynamic systems in greater detail in order to develop a better model for climate change.

Low temperature dissolution flowsheet for plutonium metal

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

Daniel, W. E.; Almond, P. M.; Rudisill, T. S.

2016-05-01

The H-Canyon flowsheet used to dissolve Pu metal for PuO 2 production utilizes boiling HNO 3. SRNL was requested to develop a complementary dissolution flowsheet at two reduced temperature ranges. The dissolution and H 2 generation rates of Pu metal were investigated using a dissolving solution at ambient temperature (20-30 °C) and for an intermediate temperature of 50-60 °C. Additionally, the testing included an investigation of the dissolution rates and characterization of the off-gas generated from the ambient temperature dissolution of carbon steel cans and the nylon bags that contain the Pu metal when charged to the dissolver.

Development and validation of a discriminative dissolution test for nimesulide suspensions.

PubMed

da Fonseca, Laís Bastos; Labastie, Márcio; de Sousa, Valéria Pereira; Volpato, Nadia Maria

2009-01-01

The dissolution test for oral dosage forms has recently widened to a variety of special dosage forms such as suspensions. For class II drugs, such as nimesulide (NMS), this study is very important because formulation problems may compromise drug bioavailability. In the present work, tests with four brands of commercially available NMS (RA, TS, TB, and TC) have been performed in order to study their dissolution at different conditions. The suspensions have been characterized relatively to particle size, pH, and density besides NMS assay and the amount of drug in solution in the suspension vehicles. The dissolution study was conducted using the following media: simulated intestinal fluid, pH 6.8, containing polysorbate 80 (P80) or sodium lauryl sulfate (SLS); phosphate buffer, pH 7.4, with P80 and aqueous solution of SLS. Concerning the quantitative analysis, the UV-VIS spectrophotometry could have been used in substitution to high-performance liquid chromatography since the methodology had been adequately validated. The influence of the drug particle size distribution was significant on the dissolution profiles of NMS formulations, confirming to be a factor that should be strictly controlled in the development of oral suspensions.

Preparation and in vitro/in vivo Evaluation of Lacidipine by Adsorption onto Fumed Silica Using Supercritical Carbon Dioxide.

PubMed

Geng, Yajie; Fu, Qiang; Guo, Bei; Li, Yun; Zhang, Xiangrong; Wang, Xianglin; Zhang, Tianhong

2016-01-01

The aim of this study was to design a silica-supported solid dispersion of lacidipine (LCDP) to enhance the dissolution rate and oral absorption using supercritical CO2 (scCO2) as a solvent. The formulation was characterized using differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy and fourier transformed infrared spectroscopy. In the dissolution test, LCDP-scCO2 formulation showed a significantly enhanced dissolution compared with LCDPsilica physical mixture and a faster dissolution rate than Lacipil® under different dissolution conditions. In an in vivo test, the area under concentration-time curve and Cmax of LCDP-scCO2 formulation was 9.23 and 23.78 fold greater than LCDP-silica physical mixture (1:15, w/w), respectively, whereas the corresponding values were 1.92 and 2.80 fold greater than Lacipil®, respectively. Our results showed that the solid dispersion prepared by supercritical fluids technology is a feasible method to enhance the oral bioavailability of LCDP.

Microenvironmental pH measurement during sodium naproxenate dissolution in acidic medium by UV/vis imaging.

PubMed

Østergaard, Jesper; Jensen, Henrik; Larsen, Susan W; Larsen, Claus; Lenke, Jim

2014-11-01

Variable dissolution from sodium salts of drugs containing a carboxylic acid group after passing the acidic environment of the stomach may affect oral bioavailability. The aim of the present proof of concept study was to investigate pH effects in relation to the dissolution of sodium naproxenate in 0.01M hydrochloric acid. For this purpose a UV/vis imaging-based approach capable of measuring microenvironmental pH in the vicinity of the solid drug compact as well as monitoring drug dissolution was developed. Using a pH indicating dye real-time spatially resolved measurement of pH was achieved. Sodium naproxenate, can significantly alter the local pH of the dissolution medium, is eventually neutralized and precipitates as the acidic species naproxen. The developed approach is considered useful for detailed studies of pH dependent dissolution phenomena in dissolution testing. Copyright © 2014 Elsevier B.V. All rights reserved.

Can dosage form-dependent food effects be predicted using biorelevant dissolution tests? Case example extended release nifedipine.

PubMed

Andreas, Cord J; Tomaszewska, Irena; Muenster, Uwe; van der Mey, Dorina; Mueck, Wolfgang; Dressman, Jennifer B

2016-08-01

Food intake is known to have various effects on gastrointestinal luminal conditions in terms of transit times, hydrodynamic forces and/or luminal fluid composition and can therefore affect the dissolution behavior of solid oral dosage forms. The aim of this study was to investigate and detect the dosage form-dependent food effect that has been observed for two extended-release formulations of nifedipine using in vitro dissolution tests. Two monolithic extended release formulations, the osmotic pump Adalat® XL 60mg and matrix-type Adalat® Eins 30mg formulation, were investigated with biorelevant dissolution methods using the USP apparatus III and IV under both simulated prandial states, and their corresponding quality control dissolution method. In vitro data were compared to published and unpublished in vivo data using deconvolution-based in vitro - in vivo correlation (IVIVC) approaches. Quality control dissolution methods tended to overestimate the dissolution rate due to the excessive solubilizing capabilities of the sodium dodecyl sulfate (SDS)-containing dissolution media. Using Level II biorelevant media the dosage form dependent food effect for nifedipine was described well when studied with the USP apparatus III, whereas the USP apparatus IV failed to detect the positive food effect for the matrix-type dosage form. It was demonstrated that biorelevant methods can serve as a useful tool during formulation development as they were able to qualitatively reflect the in vivo data. Copyright © 2016 Elsevier B.V. All rights reserved.

Initial dissolution kinetics of cocrystal of carbamazepine with nicotinamide.

PubMed

Hattori, Yusuke; Sato, Maiko; Otsuka, Makoto

2015-11-01

Objectives of this study are investigating the initial dissolution kinetics of the cocrystal of carbamazepine (CBZ) with nicotinamide (NIC) and understanding its initial dissolution process. Cocrystal solids of CBZ with NIC were prepared by co-milling and solvent evaporation methods. The formation of cocrystal solid was verified via X-ray diffraction measurement. Dissolution tests of the solids were performed using an original flow cell and ultraviolet-visible spectroscopic detector. The spectra monitored in situ were analyzed to determine the dissolved compounds separately using the classical least squares regression method. The initial dissolution profiles were interpreted using simultaneous model of dissolution and phase changes. In the initial dissolution, CBZ in the cocrystal structure dissolved in water and it was suggested that CBZ reached a metastable intermediate state simultaneously with dissolution. The cocrystal solid prepared by solvent evaporation provided a higher rate constant of the phase change than that prepared by co-milling. Our results thus support the use of evaporation as the method of choice to produce ordered cocrystal structures. We suggest that CBZ forms dihydrate during the dissolution process; however, during the initial phase of dissolution, CBZ changes to a metastable intermediate phase. © 2015 Royal Pharmaceutical Society.

Teaching Analytical Method Transfer through Developing and Validating Then Transferring Dissolution Testing Methods for Pharmaceuticals

ERIC Educational Resources Information Center

Kimaru, Irene; Koether, Marina; Chichester, Kimberly; Eaton, Lafayette

2017-01-01

Analytical method transfer (AMT) and dissolution testing are important topics required in industry that should be taught in analytical chemistry courses. Undergraduate students in senior level analytical chemistry laboratory courses at Kennesaw State University (KSU) and St. John Fisher College (SJFC) participated in development, validation, and…

Development of In Vitro-In Vivo Correlation/Relationship Modeling Approaches for Immediate Release Formulations Using Compartmental Dynamic Dissolution Data from “Golem”: A Novel Apparatus

PubMed Central

Tuszyński, Paweł K.; Polak, Sebastian; Jachowicz, Renata; Mendyk, Aleksander; Dohnal, Jiří

2015-01-01

Different batches of atorvastatin, represented by two immediate release formulation designs, were studied using a novel dynamic dissolution apparatus, simulating stomach and small intestine. A universal dissolution method was employed which simulated the physiology of human gastrointestinal tract, including the precise chyme transit behavior and biorelevant conditions. The multicompartmental dissolution data allowed direct observation and qualitative discrimination of the differences resulting from highly pH dependent dissolution behavior of the tested batches. Further evaluation of results was performed using IVIVC/IVIVR development. While satisfactory correlation could not be achieved using a conventional deconvolution based-model, promising results were obtained through the use of a nonconventional approach exploiting the complex compartmental dissolution data. PMID:26120580

Dissolution of Material and Test reactor Fuel in an H-Canyon Dissolver

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

Daniel, W. E.; Rudisill, T. S.; O'Rourke, P. E.

2017-01-26

In an amended record of decision for the management of spent nuclear fuel (SNF) at the Savannah River Site, the US Department of Energy has authorized the dissolution and recovery of U from 1000 bundles of Al-clad SNF. The SNF is fuel from domestic and foreign research reactors and is typically referred to as Material Test Reactor (MTR) fuel. Bundles of MTR fuel containing assemblies fabricated from U-Al alloys (or other U compounds) are currently dissolved using a Hg-catalyzed HNO3 flowsheet. Since the development of the existing flowsheet, improved experimental methods have been developed to more accurately characterize the offgasmore » composition and generation rate during laboratory dissolutions. Recently, these new techniques were successfully used to develop a flowsheet for the dissolution of High Flux Isotope Reactor (HFIR) fuel. Using the data from the HFIR dissolution flowsheet development and necessary laboratory experiments, the Savannah River National Laboratory (SRNL) was requested to define flowsheet conditions for the dissolution of MTR fuels. With improved offgas characterization techniques, SRNL will be able define the number of bundles of fuel which can be charged to an H-Canyon dissolver with much less conservatism.« less

Concomitant Zn-Cd and Pb retention in a carbonated fluvio-glacial deposit under both static and dynamic conditions.

PubMed

Lassabatere, Laurent; Spadini, Lorenzo; Delolme, Cécile; Février, Laureline; Galvez Cloutier, Rosa; Winiarski, Thierry

2007-11-01

The chemical and physical processes involved in the retention of 10(-2)M Zn, Pb and Cd in a calcareous medium were studied under saturated dynamic (column) and static (batch) conditions. Retention in columns decreased in order: Pb>Cd approximately Zn. In the batch experiments, the same order was observed for a contact time of less than 40h and over, Pb>Cd>Zn. Stronger Pb retention is in accordance with the lower solubility of Pb carbonates. However, the equality of retained Zn and Cd does not fit the solubility constants of carbonated solids. SEM analysis revealed that heavy metals and calcareous particles are associated. Pb precipitated as individualized Zn-Cd-Ca- free carbonated crystallites. All the heavy metals were also found to be associated with calcareous particles, without any change in their porosity, pointing to a surface/lattice diffusion-controlled substitution process. Zn and Cd were always found in concomitancy, though Pb fixed separately at the particle circumferences. The Phreeqc 2.12 interactive code was used to model experimental data on the following basis: flow fractionation in the columns, precipitation of Pb as cerrusite linked to kinetically controlled calcite dissolution, and heavy metal sorption onto proton exchanging sites (presumably surface complexation onto a calcite surface). This model simulates exchanges of metals with surface protons, pH buffering and the prevention of early Zn and Cd precipitation. Both modeling and SEM analysis show a probable significant decrease of calcite dissolution along with its contamination with metals.

Field-scale prediction of enhanced DNAPL dissolution based on partitioning tracers.

PubMed

Wang, Fang; Annable, Michael D; Jawitz, James W

2013-09-01

The equilibrium streamtube model (EST) has demonstrated the ability to accurately predict dense nonaqueous phase liquid (DNAPL) dissolution in laboratory experiments and numerical simulations. Here the model is applied to predict DNAPL dissolution at a tetrachloroethylene (PCE)-contaminated dry cleaner site, located in Jacksonville, Florida. The EST model is an analytical solution with field-measurable input parameters. Measured data from a field-scale partitioning tracer test were used to parameterize the EST model and the predicted PCE dissolution was compared to measured data from an in-situ ethanol flood. In addition, a simulated partitioning tracer test from a calibrated, three-dimensional, spatially explicit multiphase flow model (UTCHEM) was also used to parameterize the EST analytical solution. The EST ethanol prediction based on both the field partitioning tracer test and the simulation closely matched the total recovery well field ethanol data with Nash-Sutcliffe efficiency E=0.96 and 0.90, respectively. The EST PCE predictions showed a peak shift to earlier arrival times for models based on either field-measured or simulated partitioning tracer tests, resulting in poorer matches to the field PCE data in both cases. The peak shifts were concluded to be caused by well screen interval differences between the field tracer test and ethanol flood. Both the EST model and UTCHEM were also used to predict PCE aqueous dissolution under natural gradient conditions, which has a much less complex flow pattern than the forced-gradient double five spot used for the ethanol flood. The natural gradient EST predictions based on parameters determined from tracer tests conducted with a complex flow pattern underestimated the UTCHEM-simulated natural gradient total mass removal by 12% after 170 pore volumes of water flushing indicating that some mass was not detected by the tracers likely due to stagnation zones in the flow field. These findings highlight the important influence of well configuration and the associated flow patterns on dissolution. © 2013.

Field-scale prediction of enhanced DNAPL dissolution based on partitioning tracers

NASA Astrophysics Data System (ADS)

Wang, Fang; Annable, Michael D.; Jawitz, James W.

2013-09-01

The equilibrium streamtube model (EST) has demonstrated the ability to accurately predict dense nonaqueous phase liquid (DNAPL) dissolution in laboratory experiments and numerical simulations. Here the model is applied to predict DNAPL dissolution at a tetrachloroethylene (PCE)-contaminated dry cleaner site, located in Jacksonville, Florida. The EST model is an analytical solution with field-measurable input parameters. Measured data from a field-scale partitioning tracer test were used to parameterize the EST model and the predicted PCE dissolution was compared to measured data from an in-situ ethanol flood. In addition, a simulated partitioning tracer test from a calibrated, three-dimensional, spatially explicit multiphase flow model (UTCHEM) was also used to parameterize the EST analytical solution. The EST ethanol prediction based on both the field partitioning tracer test and the simulation closely matched the total recovery well field ethanol data with Nash-Sutcliffe efficiency E = 0.96 and 0.90, respectively. The EST PCE predictions showed a peak shift to earlier arrival times for models based on either field-measured or simulated partitioning tracer tests, resulting in poorer matches to the field PCE data in both cases. The peak shifts were concluded to be caused by well screen interval differences between the field tracer test and ethanol flood. Both the EST model and UTCHEM were also used to predict PCE aqueous dissolution under natural gradient conditions, which has a much less complex flow pattern than the forced-gradient double five spot used for the ethanol flood. The natural gradient EST predictions based on parameters determined from tracer tests conducted with a complex flow pattern underestimated the UTCHEM-simulated natural gradient total mass removal by 12% after 170 pore volumes of water flushing indicating that some mass was not detected by the tracers likely due to stagnation zones in the flow field. These findings highlight the important influence of well configuration and the associated flow patterns on dissolution.

DNAPL remediation with in situ chemical oxidation using potassium permanganate - Part I. Mineralogy of Mn oxide and its dissolution in organic acids

NASA Astrophysics Data System (ADS)

Li, X. David; Schwartz, Franklin W.

2004-01-01

Previous studies on in situ chemical oxidation of trichloroethylene (TCE) with potassium permanganate indicated that the solid reaction product, Mn oxide, could reduce the permeability of the porous medium and impact the success of dense non-aqueous phase liquid (DNAPL) removal. In order to address the issue of permeability reduction caused by precipitation, this study investigated the mineralogy of Mn oxides and the possibilities of removing the solid precipitates by dissolution. The solid reaction product from the oxidation of TCE by permanganate is semi-amorphous potassium-rich birnessite, which has a layered mineral structure with an interlayer spacing of 7.3 Å. The chemical formula is K 0.854Mn 1.786O 4·1.55H 2O. It has a relatively small specific surface area at 23.6±0.82 m 2/g. Its point of zero charge (pzc) was measured as 3.7±0.4. This birnessite is a relatively active species and could participate in various reactions with existing organic and inorganic matter. The dissolution kinetics of Mn oxide was evaluated in batch experiments using solutions of citric acid, oxalic acid, and ethylenediaminetetraacetic acid (EDTA). Initial dissolution rates were determined to be 0.126 mM/m 2/h for citric acid, 1.35 mM/m 2/h for oxalic acid, and 5.176 mM/m 2/h for EDTA. These rates compare with 0.0025 mM/m 2/h for nitric acid at pH=2. Organic acids dissolve Mn oxide quickly. Reaction rates increase with acid concentration, as tested with citric acid. The dissolution mechanism likely involves proton and ligand-promoted dissolution and reductive dissolution. Citric and oxalic acid can induce ligand-promoted dissolution, while EDTA can induce ligand-promoted and reductive dissolutions. At low pH, proton-promoted dissolution seems to occur with all the acids tested, but this process is not dominant. Reductive dissolution appears to be the most effective process in dissolving the solid, followed by ligand-promoted dissolution. These experiments indicate the significant potential in using these organic acids to remove precipitates formed during the oxidation reaction.

Freezing-Enhanced Dissolution of Iron Oxides: Effects of Inorganic Acid Anions.

PubMed

Jeong, Daun; Kim, Kitae; Min, Dae Wi; Choi, Wonyong

2015-11-03

Dissolution of iron from mineral dust particles greatly depends upon the type and amount of copresent inorganic anions. In this study, we investigated the roles of sulfate, chloride, nitrate, and perchlorate on the dissolution of maghemite and lepidocrocite in ice under both dark and UV irradiation and compared the results with those of their aqueous counterparts. After 96 h of reaction, the total dissolved iron in ice (pH 3 before freezing) was higher than that in the aqueous phase (pH 3) by 6-28 times and 10-20 times under dark and UV irradiation, respectively. Sulfuric acid was the most efficient in producing labile iron under dark condition, whereas hydrochloric acid induced the most dissolution of the total and ferrous iron in the presence of light. This ice-induced dissolution result was also confirmed with Arizona Test Dust (AZTD). In the freeze-thaw cycling test, the iron oxide samples containing chloride, nitrate, or perchlorate showed a similar extent of total dissolved iron after each cycling while the sulfate-containing sample rapidly lost its dissolution activity with repeating the cycle. This unique phenomenon observed in ice might be related to the freeze concentration of protons, iron oxides, and inorganic anions in the liquid-like ice grain boundary region. These results suggest that the ice-enhanced dissolution of iron oxides can be a potential source of bioavailable iron, and the acid anions critically influence this process.

Experimental characterization of composites. [load test methods

NASA Technical Reports Server (NTRS)

Bert, C. W.

1975-01-01

The experimental characterization for composite materials is generally more complicated than for ordinary homogeneous, isotropic materials because composites behave in a much more complex fashion, due to macroscopic anisotropic effects and lamination effects. Problems concerning the static uniaxial tension test for composite materials are considered along with approaches for conducting static uniaxial compression tests and static uniaxial bending tests. Studies of static shear properties are discussed, taking into account in-plane shear, twisting shear, and thickness shear. Attention is given to static multiaxial loading, systematized experimental programs for the complete characterization of static properties, and dynamic properties.

75 FR 17148 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

...] International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts... Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 7: Dissolution Test General Chapter... results of the ICH Q4B evaluation of the Dissolution Test General Chapter harmonized text from each of the...

Evaluation of various dissolution media for predicting in vivo performance of class I and II drugs.

PubMed

Galia, E; Nicolaides, E; Hörter, D; Löbenberg, R; Reppas, C; Dressman, J B

1998-05-01

In this paper we seek to verify the differences in dissolution behavior between class I and class II drugs and to evaluate the suitability of two new physiologically based media, of Simulated Gastric Fluid (SGF) and of milk for their ability to forecast trends in the in vivo performance of class II compounds and their formulations. Dissolution behavior of two class I drugs, i.e. acetaminophen and metoprolol, and of three class II drugs, i.e. danazol, mefenamic acid and ketoconazole, was studied with USP Apparatus 2 in water, SGF, milk, Simulated Intestinal Fluid without pancreatin (SIFsp) and in two media simulating the small intestinal contents in the fed (FeSSIF) and fasted (FaSSIF) states, respectively. Class I powders dissolved rapidly in all media tested. Acetaminophen dissolution in milk was slow from one tablet formulation, in all other cases dissolution was more than 85% complete in 15 minutes. The dissolution rate of metoprolol was shown to be dependent on formulation and manufacturing method, and one of the three tablet formulations did not meet compendial specifications (80%/30 minutes). Dissolution behavior of class II drugs was greatly affected by choice of medium. Dissolution from a capsule formulation of danazol proved to be dependent on the concentration of solubilizing agents, with a the 30-fold increase in percentage dissolved within 90 minutes upon changing from aqueous media without surfactants to FaSSIF. Use of FeSSIF or milk as the dissolution medium resulted in an even greater increase in percentage dissolved, 100 and 180-fold respectively. Dissolution of the weak acid mefenamic acid from a capsule formulation is dependent on both pH and bile salt concentration, which leads to an offset between increased bile salt concentration and lower pH in the fed state compared to the fasted state medium. The weak base ketoconazole showed complete dissolution from a tablet formulation in Simulated Gastric Fluid without pepsin (SGFsp) within 30 minutes, 70% dissolution in 2 hours under fed state simulated upper jejunal conditions but only 6% dissolution in 2 hours under fasted state conditions. As predicted, dissolution of class II drugs proved to be in general much more dependent on the medium than class I drugs. With the array of compendial and physiological media available, it should be possible to design a suitable set of tests to predict the in vivo dissolution of both class I and II drugs from immediate release formulations.

Alternate Fuel Cycle Technologies/Thorium Fuel Cycle Technology Programs. Quarterly report for period 1 April--30 June 1978

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

Vondra, B.L.

1978-08-01

Voloxidation and dissolution studies: rotary-kiln heat-transfer tests are under way using a small rotary kiln along with the development of a mathematical model to determine kiln-heat-flux profiles necessary to maintain a desired temperature gradient. The erosion/corrosion test for evaluating materials of construction is operational. Fuel from a BWR (Big Rock Point) yielded more fine solid residue on dissolution than in previous tests with PWR fuel. Two additional parametric voloxidation tests with H.B. Robinson fuel compared air vs pure oxygen atmospheres at 550{sup 0}C; overall tritium release and subsequent fuel dissolution were equivalent. Thorium dissolution studies: the dissolution rate of thoriamore » in fluoride-catalyzed 8 to 14 M HNO{sub 3} (100{sup 0}C) was max between 0.04 to 0.06 M HF; at higher fluoride concentrations, ThF{sub 4}.5H{sub 2}O precipitated. The rate of zircaloy dissolution continued to increase with increasing fluoride concentration. Stainless-steel-clad (Th,U)0{sub 2} fuel rods irradiated in the NRX reactor were sheared, voloxidized, and dissolved. {le}10% of the tritium was released during voloxidation in air at 600{sup 0}C. Carbon-14 removal from off-gas and fixation: carbon dioxide removal with Linde 13X molecular sieves to less than 100 ppB was experimentally verified using 300 ppM CO in air. Decontamination factors from 3000 to 7500 were obtained for CO{sub 2} removal in the gas-slurry stirred-tank reactor with CA(OH){sub 2}.or Ba(0H){sub 2}/sup .8H2O./. With Ba(OH){sub 2}.H{sub 2}0{sup 2} in a fixed-bed column, decontamination factors of about 30,000 were obtained.« less

76 FR 28131 - Federal Motor Vehicle Safety Standards; Motorcycle Helmets

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-13

..., this final rule sets a quasi-static load application rate for the helmet retention system; revises the... Analysis and Conclusion e. Quasi-Static Retention Test f. Helmet Conditioning Tolerances g. Other... it as a quasi-static test, instead of a static test. Specifying the application rate will aid...

An overview of in vitro dissolution/release methods for novel mucosal drug delivery systems.

PubMed

Jug, Mario; Hafner, Anita; Lovrić, Jasmina; Kregar, Maja Lusina; Pepić, Ivan; Vanić, Željka; Cetina-Čižmek, Biserka; Filipović-Grčić, Jelena

2018-01-05

In vitro dissolution/release tests are an important tool in the drug product development phase as well as in its quality control and the regulatory approval process. Mucosal drug delivery systems are aimed to provide both local and systemic drug action via mucosal surfaces of the body and exhibit significant differences in formulation design, as well as in their physicochemical and release characteristics. Therefore it is not possible to devise a single test system which would be suitable for release testing of such complex dosage forms. This article is aimed to provide a comprehensive review of both compendial and noncompendial methods used for in vitro dissolution/release testing of novel mucosal drug delivery systems aimed for ocular, nasal, oromucosal, vaginal and rectal administration. Copyright © 2017 Elsevier B.V. All rights reserved.

Modelling and shadowgraph imaging of cocrystal dissolution and assessment of in vitro antimicrobial activity for sulfadimidine/4-aminosalicylic acid cocrystals.

PubMed

Serrano, Dolores R; Persoons, Tim; D'Arcy, Deirdre M; Galiana, Carolina; Dea-Ayuela, Maria Auxiliadora; Healy, Anne Marie

2016-06-30

The aim of this work was to evaluate the influence of crystal habit on the dissolution and in vitro antibacterial and anitiprotozoal activity of sulfadimidine:4-aminosalicylic acid cocrystals. Cocrystals were produced via milling or solvent mediated processes. In vitro dissolution was carried out in the flow-through apparatus, with shadowgraph imaging and mechanistic mathematical models used to observe and simulate particle dissolution. In vitro activity was tested using agar diffusion assays. Cocrystallisation via milling produced small polyhedral crystals with antimicrobial activity significantly higher than sulfadimidine alone, consistent with a fast dissolution rate which was matched only by cocrystals which were milled following solvent evaporation. Cocrystallisation by solvent evaporation (ethanol, acetone) or spray drying produced flattened, plate-like or quasi-spherical cocrystals, respectively, with more hydrophobic surfaces and greater tendency to form aggregates in aqueous media, limiting both the dissolution rate and in vitro activity. Deviation from predicted dissolution profiles was attributable to aggregation behaviour, supported by observations from shadowgraph imaging. Aggregation behaviour during dissolution of cocrystals with different habits affected the dissolution rate, consistent with in vitro activity. Combining mechanistic models with shadowgraph imaging is a valuable approach for dissolution process analysis. Copyright © 2016 Elsevier B.V. All rights reserved.

Influence of the oral dissolution time on the absorption rate of locally administered solid formulations for oromucosal use: the flurbiprofen lozenges paradigm.

PubMed

Imberti, Roberto; De Gregori, Simona; Lisi, Lucia; Navarra, Pierluigi

2014-01-01

Flurbiprofen is a nonsteroidal anti-inflammatory agent preferentially used for local oromucosal treatment of painful and/or inflammatory conditions of the oropharynx such as gingivitis, stomatitis, periodontitis, pharyngitis and laryngitis. In this study, we have investigated the bioavailability of a new generic formulation of flurbiprofen lozenges developed by Epifarma Srl, compared to the originator Benactiv Gola® taken as reference. Within the framework of a formal bioequivalence study, we investigated in particular the putative influence of oral dissolution time (i.e. the time spent suckling the lozenge from its intake to complete dissolution) on the absorption rate, and the contribution of this factor to the total variability of plasma flurbiprofen during absorption. We found that the amount of flurbiprofen absorbed into the systemic circulation is not significantly higher for the test drug compared to that of the reference product. We observed that the length of oral dissolution time is inversely correlated to 10-min flurbiprofen plasma levels in the test but not in the reference formulation. We estimated that oral dissolution time accounts for about 14% of overall variability in flurbiprofen plasma 10 min after test drug administration. © 2014 S. Karger AG, Basel.

Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy.

PubMed

Rinehart, Matthew T; Drake, Tyler K; Robles, Francisco E; Rohan, Lisa C; Katz, David; Wax, Adam

2011-12-01

Quantitative phase microscopy is applied to image temporal changes in the refractive index (RI) distributions of solutions created by microbicidal films undergoing hydration. We present a novel method of using an engineered polydimethylsiloxane structure as a static phase reference to facilitate calibration of the absolute RI across the entire field. We present a study of dynamic structural changes in microbicidal films during hydration and subsequent dissolution. With assumptions about the smoothness of the phase changes induced by these films, we calculate absolute changes in the percentage of film in regions across the field of view.

Time-resolved imaging refractometry of microbicidal films using quantitative phase microscopy

PubMed Central

Rinehart, Matthew T.; Drake, Tyler K.; Robles, Francisco E.; Rohan, Lisa C.; Katz, David; Wax, Adam

2011-01-01

Quantitative phase microscopy is applied to image temporal changes in the refractive index (RI) distributions of solutions created by microbicidal films undergoing hydration. We present a novel method of using an engineered polydimethylsiloxane structure as a static phase reference to facilitate calibration of the absolute RI across the entire field. We present a study of dynamic structural changes in microbicidal films during hydration and subsequent dissolution. With assumptions about the smoothness of the phase changes induced by these films, we calculate absolute changes in the percentage of film in regions across the field of view. PMID:22191912

Model calculation of Cr dissolution behavior of ODS ferritic steel in high-temperature flowing sodium environment

NASA Astrophysics Data System (ADS)

Ohtsuka, Satoshi; Tanno, Takashi; Oka, Hiroshi; Yano, Yasuhide; Kato, Shoichi; Furukawa, Tomohiro; Kaito, Takeji

2018-07-01

A calculation model was constructed to systematically study the effects of environmental conditions (i.e. Cr concentration in sodium, test temperature, axial temperature gradient of fuel pin, and sodium flow velocity) on Cr dissolution behavior. Chromium dissolution was largely influenced by small changes in Cr concentration (i.e. chemical potential of Cr) in liquid sodium in the model calculation. Chromium concentration in sodium coolant, therefore, should be recognized as a critical parameter for the prediction and management of Cr dissolution behavior in the sodium-cooled fast reactor (SFR) core. Because the fuel column length showed no impact on dissolution behavior in the model calculation, no significant downstream effects possibly take place in the SFR fuel cladding tube due to the much shorter length compared with sodium loops in the SFR plant and the large axial temperature gradient. The calculated profile of Cr concentration along the wall-thickness direction was consistent with that measured in BOR-60 irradiation test where Cr concentration in inlet sodium bulk flow was set at 0.07 wt ppm in the calculation.

Mesoporous silica-based dosage forms improve bioavailability of poorly soluble drugs in pigs: case example fenofibrate.

PubMed

O'Shea, Joseph P; Nagarsekar, Kalpa; Wieber, Alena; Witt, Vanessa; Herbert, Elisabeth; O'Driscoll, Caitriona M; Saal, Christoph; Lubda, Dieter; Griffin, Brendan T; Dressman, Jennifer B

2017-10-01

Mesoporous silicas (SLC) have demonstrated considerable potential to improve bioavailability of poorly soluble drugs by facilitating rapid dissolution and generating supersaturation. The addition of certain polymers can further enhance the dissolution of these formulations by preventing drug precipitation. This study uses fenofibrate as a model drug to investigate the performance of an SLC-based formulation, delivered with hydroxypropyl methylcellulose acetate succinate (HPMCAS) as a precipitation inhibitor, in pigs. The ability of biorelevant dissolution testing to predict the in vivo performance was also assessed. Fenofibrate-loaded mesoporous silica (FF-SLC), together with HPMCAS, displayed significant improvements in biorelevant dissolution tests relative to a reference formulation consisting of a physical mixture of crystalline fenofibrate with HPMCAS. In vivo assessment in fasted pigs demonstrated bioavailabilities of 86.69 ± 35.37% with combination of FF-SLC and HPMCAS in capsule form and 75.47 ± 14.58% as a suspension, compared to 19.92 ± 9.89% with the reference formulation. A positive correlation was identified between bioavailability and dissolution efficiency. The substantial improvements in bioavailability of fenofibrate from the SLC-based formulations confirm the ability of this formulation strategy to overcome the dissolution and solubility limitations, further raising the prospects of a future commercially available SLC-based formulation. © 2017 Royal Pharmaceutical Society.

Correlation of dissolution and disintegration results for an immediate-release tablet.

PubMed

Nickerson, Beverly; Kong, Angela; Gerst, Paul; Kao, Shangming

2018-02-20

The drug release rate of a rapidly dissolving immediate-release tablet formulation with a highly soluble drug is proposed to be controlled by the disintegration rate of the tablet. Disintegration and dissolution test methods used to evaluate the tablets were shown to discriminate manufacturing process differences and compositionally variant tablets. In addition, a correlation was established between disintegration and dissolution. In accordance with ICH Q6A, this work demonstrates that disintegration in lieu of dissolution is suitable as the drug product quality control method for evaluating this drug product. Copyright © 2017 Elsevier B.V. All rights reserved.

Significance of a Shelf-wide Dissolution Event during the Paleocene-Eocene Thermal Maximum, Maryland and New Jersey, USA

NASA Astrophysics Data System (ADS)

Bralower, T. J.; Kump, L. R.; Robinson, M. M.; Self-Trail, J. M.; Zachos, J. C.

2016-12-01

Continental-shelf sediments of the US Atlantic margin experienced a brief episode of carbonate dissolution during the onset of the Paleocene-Eocene Thermal Maximum (PETM). Dissolution is represented by reduced percentages of carbonate, and calcareous microfossil distribution and preservation trends, in cores from Maryland and New Jersey. The base and the top of the dissolution zone are abrupt compared to the gradual nature of the onset of the carbon isotope excursion (CIE). The thickness of the dissolution zone varies from 9 cm in the Bass River core (outer paleoshelf) to 1.6 m in the CamDor core (middle paleoshelf). The decrease in %CaCO3 suggests dissolution locally removed 83 to 100% of the initial biogenic carbonate. Shelf-wide dissolution during the onset of the PETM may be a regional event, associated, for example, with eutrophication. Samples from across the paleoshelf contain abundant fine-grained framboidal pyrite, which suggests photic-zone euxinia occurred before, during, and after the dissolution event. Dissolution may also be associated with oxidation of this pyrite during later exposure to oxidizing groundwaters, although the restricted duration of the dissolution interval argues against this. Alternatively, the dissolution event may have global significance related to surface ocean-water acidification or shoaling of the calcite compensation depth (CCD) to shelf depths. The event began near the onset of the CIE on the shelf, whereas dissolution in deep-sea sections began later. Earlier shelf dissolution is consistent with surface ocean acidification while later deep-sea dissolution is thought to be associated with shoaling of the CCD. In our presentation, we weigh evidence for each of these possibilities and test them using the global dataset.

Supersaturation and crystallization: non-equilibrium dynamics of amorphous solid dispersions for oral drug delivery.

PubMed

Kawakami, Kohsaku

2017-06-01

Amorphous solid dispersions (ASDs) are one of the key formulation technologies that aid the development of poorly soluble candidates. However, their dynamic behaviors, including dissolution and crystallization processes, are still full of mystery. Further understanding of these processes should enhance their wider use. Areas covered: The first part of this review describes the current understanding of the dissolution of ASDs, where phase separation behavior is frequently involved and attempts to develop appropriate dissolution tests to achieve an in vitro-in vivo correlation are examined. The second part of this review discusses crystallization of the drug molecule with the eventual aim of establishing an accelerated testing protocol for predicting its physical stability. Expert opinion: The phase separation behavior from the supersaturated state during the dissolution test must be understood, and its relevance to the oral absorption behavior needs to be clarified. Research efforts should focus on the differences between the phase behavior in in vitro and in vivo situations. Initiation time of the crystallization was shown to be predicted only from storage and glass transition temperatures. This finding should encourage the establishment of testing protocol of the physical stability of ASDs.

Results of the recent precipitation static flight test program on the Navy P-3B antisubmarine aircraft

NASA Technical Reports Server (NTRS)

Whitaker, Mike

1991-01-01

Severe precipitation static problems affecting the communication equipment onboard the P-3B aircraft were recently studied. The study was conducted after precipitation static created potential safety-of-flight problems on Naval Reserve aircraft. A specially designed flight test program was conducted in order to measure, record, analyze, and characterize potential precipitation static problem areas. The test program successfully characterized the precipitation static interference problems while the P-3B was flown in moderate to extreme precipitation conditions. Data up to 400 MHz were collected on the effects of engine charging, precipitation static, and extreme cross fields. These data were collected using a computer controlled acquisition system consisting of a signal generator, RF spectrum and audio analyzers, data recorders, and instrumented static dischargers. The test program is outlined and the computer controlled data acquisition system is described in detail which was used during flight and ground testing. The correlation of test results is also discussed which were recorded during the flight test program and those measured during ground testing.

PEP Support: Laboratory Scale Leaching and Permeate Stability Tests

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

Russell, Renee L.; Peterson, Reid A.; Rinehart, Donald E.

2010-05-21

This report documents results from a variety of activities requested by the Hanford Tank Waste Treatment and Immobilization Plant (WTP). The activities related to caustic leaching, oxidative leaching, permeate precipitation behavior of waste as well as chromium (Cr) leaching are: • Model Input Boehmite Leaching Tests • Pretreatment Engineering Platform (PEP) Support Leaching Tests • PEP Parallel Leaching Tests • Precipitation Study Results • Cr Caustic and Oxidative Leaching Tests. Leaching test activities using the PEP simulant provided input to a boehmite dissolution model and determined the effect of temperature on mass loss during caustic leaching, the reaction rate constantmore » for the boehmite dissolution, and the effect of aeration in enhancing the chromium dissolution during caustic leaching. Other tests were performed in parallel with the PEP tests to support the development of scaling factors for caustic and oxidative leaching. Another study determined if precipitate formed in the wash solution after the caustic leach in the PEP. Finally, the leaching characteristics of different chromium compounds under different conditions were examined to determine the best one to use in further testing.« less

[Preparation and in vitro dissolution of magnolol solid dispersion].

PubMed

Tang, Lan; Qiu, Shuai-Bo; Wu, Lan; Lv, Long-Fei; Lv, Hui-Xia; Shan, Wei-Guang

2016-02-01

In this study, solid dispersion system of magnolol in croscarmellose sodium was prepared by using the solvent evaporation method, in order to increase the drug dissolution. And its dissolution behavior, stability and physical characteristics were studied. The solid dispersion was prepared with magnolol and croscarmellose sodium, with the proportion of 1∶5, the in vitro dissolution of magnolol solid dispersion was up to 80.66% at 120 min, which was 6.9 times of magnolol. The results of DSC (differential scanning calorimetry), IR (infra-red) spectrum and SEM (scanning electron microscopy) showed that magnolol existed in solid dispersion in an amorphous form. After an accelerated stability test for six months, the drug dissolution and content in magnolol solid dispersion showed no significant change. So the solid dispersion prepared with croscarmellose sodium as the carrier can remarkably improve the stability and dissolution of magnolol. Copyright© by the Chinese Pharmaceutical Association.

Dissolution behaviour of 238U, 234U and 230Th deposited on filters from personal dosemeters.

PubMed

Becková, Vera; Malátová, Irena

2008-01-01

Kinetics of dissolution of (238)U, (234)U and (230)Th dust deposited on filters from personal alpha dosemeters was studied by means of a 26-d in vitro dissolution test with a serum ultrafiltrate simulant. Dosemeters had been used by miners at the uranium mine 'Dolní Rozínka' at Rozná, Czech Republic. The sampling flow-rate as declared by the producer is 4 l h(-1) and the sampling period is typically 1 month. Studied filters contained 125 +/- 6 mBq (238)U in equilibrium with (234)U and (230)Th; no (232)Th series nuclides were found. Half-time of rapid dissolution of 1.4 d for (238)U and (234)U and slow dissolution half-times of 173 and 116 d were found for (238)U and (234)U, respectively. No detectable dissolution of (230)Th was found.

Aluminum Target Dissolution in Support of the Pu-238 Program

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

McFarlane, Joanna; Benker, Dennis; DePaoli, David W

2014-09-01

Selection of an aluminum alloy for target cladding affects post-irradiation target dissolution and separations. Recent tests with aluminum alloy 6061 yielded greater than expected precipitation in the caustic dissolution step, forming up to 10 wt.% solids of aluminum hydroxides and aluminosilicates. We present a study to maximize dissolution of aluminum metal alloy, along with silicon, magnesium, and copper impurities, through control of temperature, the rate of reagent addition, and incubation time. Aluminum phase transformations have been identified as a function of time and temperature, using X-ray diffraction. Solutions have been analyzed using wet chemical methods and X-ray fluorescence. These datamore » have been compared with published calculations of aluminum phase diagrams. Temperature logging during the transients has been investigated as a means to generate kinetic and mass transport data on the dissolution process. Approaches are given to enhance the dissolution of aluminum and aluminosilicate phases in caustic solution.« less

Accelerated Leach Testing of Glass (ALTGLASS): II. Mineralization of hydrogels by leachate strong bases

DOE PAGES

Jantzen, Carol M.; Trivelpiece, Cory L.; Crawford, Charles L.; ...

2017-02-18

The durability of high level nuclear waste glasses must be predicted on geological time scales. Waste glass surfaces form hydrogels when in contact with water for varying test durations. As the glass hydrogels age, some exhibit an undesirable resumption of dissolution at long times while others exhibit near steady-state dissolution, that is, nonresumption of dissolution. Resumption of dissolution is associated with the formation of zeolitic phases while nonresumption of dissolution is associated with the formation of clay minerals. Hydrogels with a stoichiometry close to that of imogolite, (Al 2O 3·Si(OH) 4), with ferrihydrite (Fe 2O 3·0.5H 2O), have been shownmore » to be associated with waste glasses that resume dissolution. Aluminosilicate hydrogels with a stoichiometry of allophane-hisingerite ((Al,Fe) 2O 3·1.3-2Si(OH) 4) have been shown to be associated with waste glasses that exhibit near steady-state dissolution at long times. These phases are all amorphous and poorly crystalline and are also found on natural weathered basalt glasses. Interaction of these hydrogels with excess alkali and OH – (strong base) in the leachates, causes the Al 2O 3· nSiO 2 (where n=1-2) hydrogels to mineralize to zeolites. Excess alkali in the leachate is generated by alkali in the glass. As a result, preliminary rate-determining leach layer forming exchange reactions are hypothesized based on these findings.« less

Accelerated Leach Testing of Glass (ALTGLASS): II. Mineralization of hydrogels by leachate strong bases

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

Jantzen, Carol M.; Trivelpiece, Cory L.; Crawford, Charles L.

The durability of high level nuclear waste glasses must be predicted on geological time scales. Waste glass surfaces form hydrogels when in contact with water for varying test durations. As the glass hydrogels age, some exhibit an undesirable resumption of dissolution at long times while others exhibit near steady-state dissolution, that is, nonresumption of dissolution. Resumption of dissolution is associated with the formation of zeolitic phases while nonresumption of dissolution is associated with the formation of clay minerals. Hydrogels with a stoichiometry close to that of imogolite, (Al 2O 3·Si(OH) 4), with ferrihydrite (Fe 2O 3·0.5H 2O), have been shownmore » to be associated with waste glasses that resume dissolution. Aluminosilicate hydrogels with a stoichiometry of allophane-hisingerite ((Al,Fe) 2O 3·1.3-2Si(OH) 4) have been shown to be associated with waste glasses that exhibit near steady-state dissolution at long times. These phases are all amorphous and poorly crystalline and are also found on natural weathered basalt glasses. Interaction of these hydrogels with excess alkali and OH – (strong base) in the leachates, causes the Al 2O 3· nSiO 2 (where n=1-2) hydrogels to mineralize to zeolites. Excess alkali in the leachate is generated by alkali in the glass. As a result, preliminary rate-determining leach layer forming exchange reactions are hypothesized based on these findings.« less

A Comparison of Quasi-Static Indentation Testing to Low Velocity Impact Testing

NASA Technical Reports Server (NTRS)

Nettles, Alan T.; Douglas, Michael J.

2001-01-01

The need for a static test method for modeling low-velocity foreign object impact events to composites would prove to be very beneficial to researchers since much more data can be obtained from a static test than from an impact test. In order to examine if this is feasible, a series of static indentation and low velocity impact tests were carried out and compared. Square specimens of many sizes and thickness were utilized to cover the array of types of low velocity impact events. Laminates with a n/4 stacking sequence were employed since this is by the most common type of engineering laminate. Three distinct flexural rigidities under two different boundary conditions were tested in order to obtain damage due to large deflections, contact stresses and both to examine if the static indentation-impact comparisons are valid under the spectrum of damage modes that can be experienced. Comparisons between static indentation and low velocity impact tests were based on the maximum applied transverse load. The dependent parameters examined included dent depth, back surface crack length, delamination area and to a limited extent, load-deflection behavior. Results showed that no distinct differences could be seen between the static indentation tests and the low velocity impact tests, indicating that static indentation can be used to represent a low velocity impact event.

40 CFR 53.64 - Test procedure: Static fractionator test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 5 2011-07-01 2011-07-01 false Test procedure: Static fractionator test. 53.64 Section 53.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Performance Characteristics of Class II Equivalent Methods for PM2.5 § 53.64 Test procedure: Static...

40 CFR 53.64 - Test procedure: Static fractionator test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Test procedure: Static fractionator test. 53.64 Section 53.64 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... Performance Characteristics of Class II Equivalent Methods for PM2.5 § 53.64 Test procedure: Static...

Alternative Chemical Cleaning Methods for High Level Waste Tanks: Actual Waste Testing with SRS Tank 5F Sludge

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

King, William D.; Hay, Michael S.

Solubility testing with actual High Level Waste tank sludge has been conducted in order to evaluate several alternative chemical cleaning technologies for the dissolution of sludge residuals remaining in the tanks after the exhaustion of mechanical cleaning and sludge sluicing efforts. Tests were conducted with archived Savannah River Site (SRS) radioactive sludge solids that had been retrieved from Tank 5F in order to determine the effectiveness of an optimized, dilute oxalic/nitric acid cleaning reagent toward dissolving the bulk non-radioactive waste components. Solubility tests were performed by direct sludge contact with the oxalic/nitric acid reagent and with sludge that had beenmore » pretreated and acidified with dilute nitric acid. For comparison purposes, separate samples were also contacted with pure, concentrated oxalic acid following current baseline tank chemical cleaning methods. One goal of testing with the optimized reagent was to compare the total amounts of oxalic acid and water required for sludge dissolution using the baseline and optimized cleaning methods. A second objective was to compare the two methods with regard to the dissolution of actinide species known to be drivers for SRS tank closure Performance Assessments (PA). Additionally, solubility tests were conducted with Tank 5 sludge using acidic and caustic permanganate-based methods focused on the “targeted” dissolution of actinide species.« less

Influence of pH, particle size and crystal form on dissolution behaviour of engineered nanomaterials.

PubMed

Avramescu, M-L; Rasmussen, P E; Chénier, M; Gardner, H D

2017-01-01

Solubility is a critical component of physicochemical characterisation of engineered nanomaterials (ENMs) and an important parameter in their risk assessments. Standard testing methodologies are needed to estimate the dissolution behaviour and biodurability (half-life) of ENMs in biological fluids. The effect of pH, particle size and crystal form on dissolution behaviour of zinc metal, ZnO and TiO 2 was investigated using a simple 2 h solubility assay at body temperature (37 °C) and two pH conditions (1.5 and 7) to approximately frame the pH range found in human body fluids. Time series dissolution experiments were then conducted to determine rate constants and half-lives. Dissolution characteristics of investigated ENMs were compared with those of their bulk analogues for both pH conditions. Two crystal forms of TiO 2 were considered: anatase and rutile. For all compounds studied, and at both pH conditions, the short solubility assays and the time series experiments consistently showed that biodurability of the bulk analogues was equal to or greater than biodurability of the corresponding nanomaterials. The results showed that particle size and crystal form of inorganic ENMs were important properties that influenced dissolution behaviour and biodurability. All ENMs and bulk analogues displayed significantly higher solubility at low pH than at neutral pH. In the context of classification and read-across approaches, the pH of the dissolution medium was the key parameter. The main implication is that pH and temperature should be specified in solubility testing when evaluating ENM dissolution in human body fluids, even for preliminary (tier 1) screening.

In silico prediction of drug dissolution and absorption with variation in intestinal pH for BCS class II weak acid drugs: ibuprofen and ketoprofen.

PubMed

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L

2012-10-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS class III and BCS class II have been proposed, in particular, BCS class II weak acids. However, a discrepancy between the in vivo BE results and in vitro dissolution results for BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH of 6.0. Further the experimental dissolution of ibuprofen tablets in a low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol l (-1) /pH) was dramatically reduced compared with the dissolution in SIF (the average buffer capacity 12.6 mmol l (-1) /pH). Thus these predictions for the oral absorption of BCS class II acids indicate that the absorption patterns depend largely on the intestinal pH and buffer strength and must be considered carefully for a bioequivalence test. Simulation software may be a very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. Copyright © 2012 John Wiley & Sons, Ltd.

In Silico Prediction of Drug Dissolution and Absorption with variation in Intestinal pH for BCS Class II Weak Acid Drugs: Ibuprofen and Ketoprofen§

PubMed Central

Tsume, Yasuhiro; Langguth, Peter; Garcia-Arieta, Alfredo; Amidon, Gordon L.

2012-01-01

The FDA Biopharmaceutical Classification System guidance allows waivers for in vivo bioavailability and bioequivalence studies for immediate-release solid oral dosage forms only for BCS class I. Extensions of the in vivo biowaiver for a number of drugs in BCS Class III and BCS class II have been proposed, particularly, BCS class II weak acids. However, a discrepancy between the in vivo- BE results and in vitro- dissolution results for a BCS class II acids was recently observed. The objectives of this study were to determine the oral absorption of BCS class II weak acids via simulation software and to determine if the in vitro dissolution test with various dissolution media could be sufficient for in vitro bioequivalence studies of ibuprofen and ketoprofen as models of carboxylic acid drugs. The oral absorption of these BCS class II acids from the gastrointestinal tract was predicted by GastroPlus™. Ibuprofen did not satisfy the bioequivalence criteria at lower settings of intestinal pH=6.0. Further the experimental dissolution of ibuprofen tablets in the low concentration phosphate buffer at pH 6.0 (the average buffer capacity 2.2 mmol L-1/pH) was dramatically reduced compared to the dissolution in SIF (the average buffer capacity 12.6 mmol L -1/pH). Thus these predictions for oral absorption of BCS class II acids indicate that the absorption patterns largely depend on the intestinal pH and buffer strength and must be carefully considered for a bioequivalence test. Simulation software may be very useful tool to aid the selection of dissolution media that may be useful in setting an in vitro bioequivalence dissolution standard. PMID:22815122

Level A in vitro-in vivo correlation: Application to establish a dissolution test for artemether and lumefantrine tablets.

PubMed

Rivelli, Graziella Gomes; Ricoy, Letícia Brandão Magalhães; César, Isabela Costa; Fernandes, Christian; Pianetti, Gérson Antônio

2018-06-05

Malaria is the most incident parasite infection worldwide. Artemisinin based combination therapy (ACT) has been proposed as a promising treatment for malaria, and artemether + lumefantrine (20 + 120 mg) is the recommended association in endemic areas. Despite its widespread use, there is still scarce information about dissolution of artemether and lumefantrine, reflecting in the absence of a specific method in pharmacopoeias and international compendia. Because the of their low solubility, both artemether and lumefantrine are candidates for in vitro-in vivo correlation (IVIVC) studies. Previous equilibrium solubility studies have been carried out for both drugs using the shake-flask method and dissolution profiles. Experiments were conducted with a range of parameters such as medium composition, pH and surfactants. In vivo data obtained in a previous pharmacokinetic study was used to select the optimum conditions for dissolution test, based on IVIVC. For drug quantitation, a selective method by high performance liquid chromatography was optimized and validated. For this dosage form, the best dissolution conditions found for artemether were: paddles, 900 mL of dissolution medium containing phosphate buffer pH 6.8 with 1.0% sodium lauryl sulfate and rotation speed of 100 rpm. The same was obtained for lumefantrine, except the dissolution medium, which was pH 1.2 with 1.0% polysorbate 80. After obtaining the curve of in vitro dissolved fraction versus in vivo absorbed fraction, the calculated coefficient of determination (R squared) was close to 1.00 for both drugs, indicating a level A correlation. Therefore, a novel method for assessing dissolution of arthemeter and lumefantrine tablets was established and validated. Copyright © 2018 Elsevier B.V. All rights reserved.

A Quality by Design approach to investigate tablet dissolution shift upon accelerated stability by multivariate methods.

PubMed

Huang, Jun; Goolcharran, Chimanlall; Ghosh, Krishnendu

2011-05-01

This paper presents the use of experimental design, optimization and multivariate techniques to investigate root-cause of tablet dissolution shift (slow-down) upon stability and develop control strategies for a drug product during formulation and process development. The effectiveness and usefulness of these methodologies were demonstrated through two application examples. In both applications, dissolution slow-down was observed during a 4-week accelerated stability test under 51°C/75%RH storage condition. In Application I, an experimental design was carried out to evaluate the interactions and effects of the design factors on critical quality attribute (CQA) of dissolution upon stability. The design space was studied by design of experiment (DOE) and multivariate analysis to ensure desired dissolution profile and minimal dissolution shift upon stability. Multivariate techniques, such as multi-way principal component analysis (MPCA) of the entire dissolution profiles upon stability, were performed to reveal batch relationships and to evaluate the impact of design factors on dissolution. In Application II, an experiment was conducted to study the impact of varying tablet breaking force on dissolution upon stability utilizing MPCA. It was demonstrated that the use of multivariate methods, defined as Quality by Design (QbD) principles and tools in ICH-Q8 guidance, provides an effective means to achieve a greater understanding of tablet dissolution upon stability. Copyright © 2010 Elsevier B.V. All rights reserved.

Contact Angle Measurements: an Alternative Approach Towards Understanding the Mechanism of Increased Drug Dissolution from Ethylcellulose Tablets Containing Surfactant and Exploring the Relationship Between Their Contact Angles and Dissolution Behaviors.

PubMed

Liu, Tiaotiao; Hao, Jingqiang; Yang, Baixue; Hu, Beibei; Cui, Zhixiang; Li, Sanming

2018-05-01

The addition of surfactant in tablet was a well-defined approach to improve drug dissolution rate. While the selected surfactant played a vital role in improving the wettability of tablet by medium, it was equally important to improve the dissolution rate by permeation effect due to production of pores or the reduced inter-particle adhesion. Furthermore, understanding the mechanism of dissolution rate increased was significant. In this work, contact angle measurement was taken up as an alternative approach for understanding the dissolution rate enhancement for tablet containing surfactant. Ethylcellulose, as a substrate, was used to prepare tablet. Four surfactants, sodium dodecyl sulfate (SDS), sodium dodecylbenzenesulfonate (SDBS), dodecyltrimethylammonium bromide (DTAB), and sodium lauryl sulfonate (SLS), were used. Berberine hydrochloride, metformin hydrochloride, and rutin were selected as model drugs. The contact angle of tablet in the absence and presence of surfactant was measured to explore the mechanism. The dissolution test was investigated to verify the mechanism and to establish a correlation with the contact angle. The result showed that the mechanism was the penetration effect rather than the wetting effect. The dissolution increased with a reduction in the contact angle. DTAB was found to obtain the highest level of dissolution enhancement and the lowest contact angle, while SDS, SDBS, and SLS were found to be the less effective in both dissolution enhancement and contact angle decrease. Therefore, contact angle was a good indicator for dissolution behavior besides exploring the mechanism of increased dissolution, which shows great potential in formula screening.

Vertical Force-deflection Characteristics of a Pair of 56-inch-diameter Aircraft Tires from Static and Drop Tests with and Without Prerotation

NASA Technical Reports Server (NTRS)

Smiley, Robert F; Horne, Walter B

1957-01-01

The vertical force-deflection characteristics were experimentally determined for a pair of 56-inch-diameter tires under static and drop-test conditions with and without prerotation. For increasing force, the tires were found to be least stiff for static tests, almost the same as for the static case for prerotation drop tests as long as the tires remain rotating, and appreciably stiffer for drop tests without prerotation.

Electrochemical polishing of thread fastener test specimens of nickel-chromium iron alloys

DOEpatents

Kephart, Alan R.

1991-01-01

An electrochemical polishing device and method for selective anodic dissolution of the surface of test specimens comprised, for example, of nickel-chromium-iron alloys, which provides for uniform dissolution at the localized sites to remove metal through the use of a coiled wire electrode (cathode) placed in the immediate proximity of the working, surface resulting in a polished and uniform grain boundary.

Assessment of Marine Coatings at a Central California Static Immersion Test Site

DTIC Science & Technology

2016-10-27

VA 220600-6218 RE: Contract Number N00014-15-1-2321 Assessment of Marine Coatings at a Central California Static Immersion Test Site Principal...Technical Report 05/01/2015 - 07/29/2016 Assessment of Marine Coatings at a Central California Static Immersion Test Site Dean E. Wendt Cal Poly...to test the relationships between the recruitment of fouling organisms to intersite panels and water quality parameters. The static immersion site

Effect of inlet disturbances on fan inlet noise during a static test

NASA Technical Reports Server (NTRS)

Bekofske, K. L.; Sheer, R. E., Jr.; Wang, J. C. F.

1977-01-01

Measurements of fan rotor inlet noise taken during static test situations are at variance with aircraft engine flight data. In particular, static tests generally yield a significantly higher tone at blade passage frequency than that measured during flight. To explain this discrepancy, the extent of the influence of inlet ground vortices and large-scale inlet turbulence on the forward-radiated fan noise measured at a static test facility was investigated. While such inlet disturbances were generated intentionally in an anechoic test chamber, far-field acoustic measurements and inlet flow-field hot-film mappings of a fan rotor were obtained. Experimental results indicate that the acoustic effect of such disturbances appears to be less severe for supersonic than for subsonic tip speeds. Further, a reverse flow that occurs on the exterior cowl in static test facilities appears to be an additional prime candidate for creating inlet disturbances and causing variance between flight and static acoustic data.

Investigation of Deteriorated Dissolution of Amorphous Itraconazole: Description of Incompatibility with Magnesium Stearate and Possible Solutions.

PubMed

Démuth, B; Galata, D L; Szabó, E; Nagy, B; Farkas, A; Balogh, A; Hirsch, E; Pataki, H; Rapi, Z; Bezúr, L; Vigh, T; Verreck, G; Szalay, Z; Demeter, Á; Marosi, G; Nagy, Z K

2017-11-06

Disadvantageous crystallization phenomenon of amorphous itraconazole (ITR) occurring in the course of dissolution process was investigated in this work. A perfectly amorphous form (solid dispersion) of the drug was generated by the electroblowing method (with vinylpyrrolidone-vinyl acetate copolymer), and the obtained fibers were formulated into tablets. Incomplete dissolution of the tablets was noticed under the circumstances of the standard dissolution test, after which a precipitated material could be filtered. The filtrate consisted of ITR and stearic acid since no magnesium content was detectable in it. In parallel with dissolution, ITR forms an insoluble associate, stabilized by hydrogen bonding, with stearic acid deriving from magnesium stearate. This is why dissolution curves do not have the plateaus at 100%. Two ways are viable to tackle this issue: change the lubricant (with sodium stearyl fumarate >95% dissolution can be accomplished) or alter the polymer in the solid dispersion to a type being able to form hydrogen bonds with ITR (e.g., hydroxypropyl methylcellulose). This work draws attention to one possible phenomenon that can lead to a deterioration of originally good dissolution of an amorphous solid dispersion.

Health behaviors and union dissolution among parents of young children: Differences by marital status

PubMed Central

Meyer, Jess M.

2017-01-01

Previous research finds that marriage is associated with better health and lower mortality, and one of the mechanisms underlying this association is health-related selection out of marriage. Using longitudinal survey data from 2,348 couples from the Fragile Families and Child Wellbeing Study, we examine whether certain health behaviors—smoking and binge drinking—are associated with risk of union dissolution among couples with young children. We use discrete time hazard models to test whether associations between health behaviors and union dissolution differ between married and cohabiting parents. We find no statistically significant association between binge drinking and union dissolution for either cohabiting or married couples. Parental smoking, however, is associated with union dissolution. On average, married and cohabiting couples in which both parents smoke have a higher risk of union dissolution than couples in which neither parent smokes. Additionally, father’s smoking (in couples in which the mother does not smoke) is associated with union dissolution, but only for married couples. These findings illustrate the importance of considering the health behaviors of both partners and provide further evidence of differences in union dissolution dynamics between married and cohabiting couples. PMID:28796826

Health behaviors and union dissolution among parents of young children: Differences by marital status.

PubMed

Meyer, Jess M; Percheski, Christine

2017-01-01

Previous research finds that marriage is associated with better health and lower mortality, and one of the mechanisms underlying this association is health-related selection out of marriage. Using longitudinal survey data from 2,348 couples from the Fragile Families and Child Wellbeing Study, we examine whether certain health behaviors-smoking and binge drinking-are associated with risk of union dissolution among couples with young children. We use discrete time hazard models to test whether associations between health behaviors and union dissolution differ between married and cohabiting parents. We find no statistically significant association between binge drinking and union dissolution for either cohabiting or married couples. Parental smoking, however, is associated with union dissolution. On average, married and cohabiting couples in which both parents smoke have a higher risk of union dissolution than couples in which neither parent smokes. Additionally, father's smoking (in couples in which the mother does not smoke) is associated with union dissolution, but only for married couples. These findings illustrate the importance of considering the health behaviors of both partners and provide further evidence of differences in union dissolution dynamics between married and cohabiting couples.

33 CFR 183.580 - Static pressure test for fuel tanks.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 2 2012-07-01 2012-07-01 false Static pressure test for fuel... SECURITY (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Tests § 183.580 Static pressure test for fuel tanks. A fuel tank is tested by performing the following procedures in the following...

33 CFR 183.580 - Static pressure test for fuel tanks.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 2 2013-07-01 2013-07-01 false Static pressure test for fuel... SECURITY (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Tests § 183.580 Static pressure test for fuel tanks. A fuel tank is tested by performing the following procedures in the following...

33 CFR 183.580 - Static pressure test for fuel tanks.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Static pressure test for fuel... SECURITY (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Tests § 183.580 Static pressure test for fuel tanks. A fuel tank is tested by performing the following procedures in the following...

33 CFR 183.580 - Static pressure test for fuel tanks.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Static pressure test for fuel... SECURITY (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Tests § 183.580 Static pressure test for fuel tanks. A fuel tank is tested by performing the following procedures in the following...

33 CFR 183.580 - Static pressure test for fuel tanks.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Static pressure test for fuel... SECURITY (CONTINUED) BOATING SAFETY BOATS AND ASSOCIATED EQUIPMENT Fuel Systems Tests § 183.580 Static pressure test for fuel tanks. A fuel tank is tested by performing the following procedures in the following...

GENERAL VIEW LOOKING NORTHWEST AT THE SATURN V STATIC TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

GENERAL VIEW LOOKING NORTHWEST AT THE SATURN V STATIC TEST FACILITY. THIS TEST FACILITY WAS DESIGNED TO RESIST THE 12 MILLION POUNDES OF THRUST GENERATED BY THE THE SATURN V FIRST STAGE ENGINE CLUSTER. - Marshall Space Flight Center, Saturn V S-IC Static Test Facility, West Test Area, Huntsville, Madison County, AL

An understanding of modified release matrix tablets behavior during drug dissolution as the key for prediction of pharmaceutical product performance - case study of multimodal characterization of quetiapine fumarate tablets.

PubMed

Kulinowski, Piotr; Woyna-Orlewicz, Krzysztof; Rappen, Gerd-Martin; Haznar-Garbacz, Dorota; Węglarz, Władysław P; Dorożyński, Przemysław P

2015-04-30

Motivation for the study was the lack of dedicated and effective research and development (R&D) in vitro methods for oral, generic, modified release formulations. The purpose of the research was to assess multimodal in vitro methodology for further bioequivalence study risk minimization. Principal results of the study are as follows: (i) Pharmaceutically equivalent quetiapine fumarate extended release dosage form of Seroquel XR was developed using a quality by design/design of experiment (QbD/DoE) paradigm. (ii) The developed formulation was then compared with originator using X-ray microtomography, magnetic resonance imaging and texture analysis. Despite similarity in terms of compendial dissolution test, developed and original dosage forms differed in micro/meso structure and consequently in mechanical properties. (iii) These differences were found to be the key factors of failure of biorelevant dissolution test using the stress dissolution apparatus. Major conclusions are as follows: (i) Imaging methods allow to assess internal features of the hydrating extended release matrix and together with the stress dissolution test allow to rationalize the design of generic formulations at the in vitro level. (ii) Technological impact on formulation properties e.g., on pore formation in hydrating matrices cannot be overlooked when designing modified release dosage forms. Copyright © 2015 Elsevier B.V. All rights reserved.

Consumer vinegar test for determining calcium disintegration.

PubMed

Mason, N A; Patel, J D; Dressman, J B; Shimp, L A

1992-09-01

A consumer test and standardized methods were compared for measuring the disintegration of calcium tablets, and the disintegration results were compared with results of dissolution testing to determine the ability of the consumer test of disintegration to predict bioavailability of calcium. Disintegration of 17 calcium supplement products, in tablet form, was studied in Simulated Gastric Fluid Test Solution, USP, without pepsin (GF), in distilled water, and in white distilled vinegar. For disintegration testing with GF and with distilled water, six tablets of each product were placed in an apparatus and immersed in the solution at 37 degrees C for 60 minutes. Six tablets of each product were tested in 200 mL of vinegar at room temperature for 30 minutes. Disintegration was determined by visual observation. Seven products were tested for dissolution in GF or water. Three samples of each product were tested at intervals over 120 minutes for calcium content. Results of testing with an ion-selective electrode were converted to milligrams and compared with the calcium content of the tablets (as claimed on the package label). The mean disintegration times of various calcium products in vinegar ranged from 1.8 to greater than 30 minutes. The mean time in distilled water and GF ranged from 1.6 to greater than 60 minutes and from 1.0 to greater than 60 minutes, respectively. Results were in agreement in 87% to 93% of cases between the consumer vinegar test and the standardized disintegration test methods, a significant correlation. No correlation was found between disintegration time and the extent of dissolution. The disintegration and dissolution of commercially available calcium tablets was highly variable.(ABSTRACT TRUNCATED AT 250 WORDS)

Carbon storage potential of Columbia River flood basalt

NASA Astrophysics Data System (ADS)

Wells, R. K.; Xiong, W.; Giammar, D.; Skemer, P. A.

2017-12-01

Basalt reservoirs are an important option for sequestering carbon through dissolution of host rock and precipitation of stable carbonate minerals. This study seeks to understand the nature of dissolution and surface roughening processes and their influence on the timing and spatial distribution of carbonation, in static experiments at 150 °C and 100 bar CO2. Intact samples and cores with milled pathways from Ca-rich and Fe-rich Columbia River flood basalt formations were reacted for up to 40 weeks. Experimental specimens were analyzed using SEM-EDS, microprobe, and μCT scanning, Raman spectroscopy, and 2D profilometer to characterize changes in composition and surface roughness. ICP-MS was used to examine bulk fluid chemistry. Initial dissolution of olivine grains results in higher Mg2+ and Fe2+ concentrations within the bulk solution in the first week of reaction. However, once available olivine grains are gone, Ca-rich pyroxene becomes the primary contributor of Ca2+, Mg2+, and Fe2+ within the bulk solution. The complete dissolution of olivine grains resulted in pits up to 200 μm deep. Dissolution of other minerals resulted in the formation of microscale textures, primarily along grain boundaries and fractures. The surface roughness increased by factors of up to 42, while surface area increased 20%. Based on these results, pyroxene is the sustaining contributor of divalent metal cations during dissolution of basalt, and the limited connectivity of olivine and pyroxene grains limits the exposure of new reactive surface areas. Within 6 weeks, aragonite precipitated in Ca-rich basalt samples, while Fe-rich samples precipitated of siderite. The highest concentration of carbonates occurs 1/3 into milled pathways, which simulate dead-end fractures, in low porosity basalts, and near the fracture tip in high porosity basalts. Even at elevated temperatures, the fractures are not blocked nor filled within 40 weeks of reaction. When vesicles are present, carbonates can precipitate within these pores even when the pores do not appear to connect to the main fracture pathway. Based on our experimental results, we estimate the carbon storage potential of the Ca-rich formations within the Columbia River flood basalt to be 47 kg CO2/m3, which could be reached in 38 years at a constant carbonation rate of 1.24 ± 0.54 kg CO2/m3yr.

Comparative Tests of Pitot-static Tubes

NASA Technical Reports Server (NTRS)

Merriam, Kenneth G; Spaulding, Ellis R

1935-01-01

Comparative tests were made on seven conventional Pitot-static tubes to determine their static, dynamic, and resultant errors. The effect of varying the dynamic opening, static opening, wall thickness, and inner-tube diameter was investigated. Pressure-distribution measurements showing stem and tip effects were also made. A tentative design for a standard Pitot-static tube for use in measuring air velocity is submitted.

Finite element modeling of ROPS in static testing and rear overturns.

PubMed

Harris, J R; Mucino, V H; Etherton, J R; Snyder, K A; Means, K H

2000-08-01

Even with the technological advances of the last several decades, agricultural production remains one of the most hazardous occupations in the United States. Death due to tractor rollover is a prime contributor to this hazard. Standards for rollover protective structures (ROPS) performance and certification have been developed by groups such as the Society of Automotive Engineers (SAE) and the American Society of Agricultural Engineers (ASAE) to combat these problems. The current ROPS certification standard, SAE J2194, requires either a dynamic or static testing sequence or both. Although some ROPS manufacturers perform both the dynamic and static phases of SAE J2194 testing, it is possible for a ROPS to be certified for field operation using static testing alone. This research compared ROPS deformation response from a simulated SAE J2194 static loading sequence to ROPS deformation response as a result of a simulated rearward tractor rollover. Finite element analysis techniques for plastic deformation were used to simulate both the static and dynamic rear rollover scenarios. Stress results from the rear rollover model were compared to results from simulated static testing per SAE J2194. Maximum stress values from simulated rear rollovers exceeded maximum stress values recorded during simulated static testing for half of the elements comprising the uprights. In the worst case, the static model underpredicts dynamic model results by approximately 7%. In the best case, the static model overpredicts dynamic model results by approximately 32%. These results suggest the need for additional experimental work to characterize ROPS stress levels during staged overturns and during testing according to the SAE standard.

30 CFR 7.307 - Static pressure test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Static pressure test. 7.307 Section 7.307 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.307 Static...

A Comparison of Quasi-Static Indentation to Low-Velocity Impact

NASA Technical Reports Server (NTRS)

Nettles, A. T.; Douglas, M. J.

2000-01-01

A static test method for modeling low-velocity foreign object impact events to composites would prove to be very beneficial to researchers since much more data can be obtained from a static test than from an impact test. In order to examine if this is feasible, a series of static indentation and low-velocity impact tests were carried out and compared. Square specimens of many sizes and thicknesses were utilized to cover the array of types of low velocity impact events. Laminates with a pi/4 stacking sequence were employed since this is by far the most common type of engineering laminate. Three distinct flexural rigidities -under two different boundary conditions were tested in order to obtain damage ranging from that due to large deflection to contact stresses and levels in-between to examine if the static indentation-impact comparisons are valid under the spectrum of damage modes that can be experienced. Comparisons between static indentation and low-velocity impact tests were based on the maximum applied transverse load. The dependent parameters examined included dent depth, back surface crack length, delamination area, and to a limited extent, load-deflection behavior. Results showed that no distinct differences could be seen between the static indentation tests and the low-velocity impact tests, indicating that static indentation can be used to represent a low-velocity impact event.

Computational hydrodynamic comparison of a mini vessel and a USP 2 dissolution testing system to predict the dynamic operating conditions for similarity of dissolution performance.

PubMed

Wang, Bing; Bredael, Gerard; Armenante, Piero M

2018-03-25

The hydrodynamic characteristics of a mini vessel and a USP 2 dissolution testing system were obtained and compared to predict the tablet-liquid mass transfer coefficient from velocity distributions near the tablet and establish the dynamic operating conditions under which dissolution in mini vessels could be conducted to generate concentration profiles similar to those in the USP 2. Velocity profiles were obtained experimentally using Particle Image Velocimetry (PIV). Computational Fluid Dynamics (CFD) was used to predict the velocity distribution and strain rate around a model tablet. A CFD-based mass transfer model was also developed. When plotted against strain rate, the predicted tablet-liquid mass transfer coefficient was found to be independent of the system where it was obtained, implying that a tablet would dissolve at the same rate in both systems provided that the concentration gradient between the tablet surface and the bulk is the same, the tablet surface area per unit liquid volume is identical, and the two systems are operated at the appropriate agitation speeds specified in this work. The results of this work will help dissolution scientists operate mini vessels so as to predict the dissolution profiles in the USP 2, especially during the early stages of drug development. Copyright © 2018 Elsevier B.V. All rights reserved.

Chemical structure influence on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux.

PubMed

Padgett, Mark C; Tick, Geoffrey R; Carroll, Kenneth C; Burke, William R

2017-03-01

The influence of chemical structure on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux was examined. The variability of measured and UNIFAC modeled NAPL activity coefficients as a function of mole fraction was compared for two NAPL mixtures containing structurally-different contaminants of concern including toluene (TOL) or trichloroethene (TCE) within a hexadecane (HEXDEC) matrix. The results showed that dissolution from the NAPL mixtures transitioned from ideality for mole fractions >0.05 to nonideality as mole fractions decreased. In particular, the TCE generally exhibited more ideal dissolution behavior except at lower mole fractions, and may indicate greater structural/polarity similarity between the two compounds. Raoult's Law and UNIFAC generally under-predicted the batch experiment results for TOL:HEXDEC mixtures especially for mole fractions ≤0.05. The dissolution rate coefficients were similar for both TOL and TCE over all mole fractions tested. Mass flux reduction (MFR) analysis showed that more efficient removal behavior occurred for TOL and TCE with larger mole fractions compared to the lower initial mole fraction mixtures (i.e. <0.2). However, compared to TOL, TCE generally exhibited more efficient removal behavior over all mole fractions tested and may have been the result of structural and molecular property differences between the compounds. Activity coefficient variability as a function of mole fraction was quantified through regression analysis and incorporated into dissolution modeling analyses for the dynamic flushing experiments. TOL elution concentrations were modeled (predicted) reasonable well using ideal and equilibrium assumptions, but the TCE elution concentrations could not be predicted using the ideal model. Rather, the dissolution modeling demonstrated that TCE elution was better described by the nonideal model whereby NAPL-phase activity coefficient varied as a function of COC mole fraction. For dynamic column flushing experiments, dissolution rate kinetics can vary significantly with changes in NAPL volume and surface area. However, under conditions whereby NAPL volume and area are not significantly altered during dissolution, mixture nonideality effects may have a greater relative control on dissolution (elution) and MFR behavior compared to kinetic rate limitations. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical structure influence on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux

NASA Astrophysics Data System (ADS)

Padgett, Mark C.; Tick, Geoffrey R.; Carroll, Kenneth C.; Burke, William R.

2017-03-01

The influence of chemical structure on NAPL mixture nonideality evolution, rate-limited dissolution, and contaminant mass flux was examined. The variability of measured and UNIFAC modeled NAPL activity coefficients as a function of mole fraction was compared for two NAPL mixtures containing structurally-different contaminants of concern including toluene (TOL) or trichloroethene (TCE) within a hexadecane (HEXDEC) matrix. The results showed that dissolution from the NAPL mixtures transitioned from ideality for mole fractions > 0.05 to nonideality as mole fractions decreased. In particular, the TCE generally exhibited more ideal dissolution behavior except at lower mole fractions, and may indicate greater structural/polarity similarity between the two compounds. Raoult's Law and UNIFAC generally under-predicted the batch experiment results for TOL:HEXDEC mixtures especially for mole fractions ≤ 0.05. The dissolution rate coefficients were similar for both TOL and TCE over all mole fractions tested. Mass flux reduction (MFR) analysis showed that more efficient removal behavior occurred for TOL and TCE with larger mole fractions compared to the lower initial mole fraction mixtures (i.e. < 0.2). However, compared to TOL, TCE generally exhibited more efficient removal behavior over all mole fractions tested and may have been the result of structural and molecular property differences between the compounds. Activity coefficient variability as a function of mole fraction was quantified through regression analysis and incorporated into dissolution modeling analyses for the dynamic flushing experiments. TOL elution concentrations were modeled (predicted) reasonable well using ideal and equilibrium assumptions, but the TCE elution concentrations could not be predicted using the ideal model. Rather, the dissolution modeling demonstrated that TCE elution was better described by the nonideal model whereby NAPL-phase activity coefficient varied as a function of COC mole fraction. For dynamic column flushing experiments, dissolution rate kinetics can vary significantly with changes in NAPL volume and surface area. However, under conditions whereby NAPL volume and area are not significantly altered during dissolution, mixture nonideality effects may have a greater relative control on dissolution (elution) and MFR behavior compared to kinetic rate limitations.

MRI studies of the hydrodynamics in a USP 4 dissolution testing cell.

PubMed

Shiko, G; Gladden, L F; Sederman, A J; Connolly, P C; Butler, J M

2011-03-01

We present a detailed study of hydrodynamics inside the flow-through dissolution apparatus when operated according to USP recommendations. The pulsatile flow inside the flow-through cell was measured quantitatively using magnetic resonance imaging (MRI) at a spatial resolution of 234 × 234 μm(2) and slice thickness of 1 mm. We report the experimental protocols developed for in situ MRI studies and the effect that the operating conditions and tablet orientation have on the hydrodynamics inside commercial flow cells. It was found that the flow field inside the dissolution cells was, at most operating conditions, heterogeneous, rather than fully developed laminar flow, and characterised by re-circulation and backward flow. A model tablet was shown to be contacted by a wide distribution of local velocities as a function of position and orientation in the flow cell. The use of 1 mm beads acted as a distributor of the flow but did not suffice to ensure a fully developed laminar flow profile. These results emphasise the necessity to understand the influence of test conditions on dissolution behaviour in defining robust flow-through dissolution methods. Copyright © 2010 Wiley-Liss, Inc.

Technical Evaluation Motor No. 10 (TEM-10)

NASA Technical Reports Server (NTRS)

1993-01-01

Technical Evaluation Motor No. 10 (TEM-10) was static fired on 27 Apr. 1993 at the Thiokol Corporation full-scale motor static test bay, T-24. This final test report documents the procedures, performance, and results of the static test firing of TEM-10. All observations, discussions, conclusions, and recommendations contained are final. Included is a presentation and discussion of TEM-10 performance, anomalies, and test results in concurrence with the objectives outlined in CTP-0110, Revision D, Space Shuttle Technical Evaluation Motor No. 10 (TEM-10) Static Fire Test Plan.

Wind-Tunnel Tests of Seven Static-Pressure Probes at Transonic Speeds

NASA Technical Reports Server (NTRS)

Capone, Francis J.

1961-01-01

Wind-tunnel tests have been conducted to determine the errors of 3 seven static-pressure probes mounted very close to the nose of a body of revolution simulating a missile forebody. The tests were conducted at Mach numbers from 0.80 to 1.08 and at angles of attack from -1.7 deg to 8.4 deg. The test Reynolds number per foot varied from 3.35 x 10(exp 6) to 4.05 x 10(exp 6). For three 4-vane, gimbaled probes, the static-pressure errors remained constant throughout the test angle-of-attack range for all Mach numbers except 1.02. For two single-vane, self-rotating probes having two orifices at +/-37.5 deg. from the plane of symmetry on the lower surface of the probe body, the static-pressure error varied as much as 1.5 percent of free-stream static pressure through the test angle-of- attack range for all Mach numbers. For two fixed, cone-cylinder probes of short length and large diameter, the static-pressure error varied over the test angle-of-attack range at constant Mach numbers as much as 8 to 10 percent of free-stream static pressure.

In vitro dissolution of generic immediate-release solid oral dosage forms containing BCS class I drugs: comparative assessment of metronidazole, zidovudine, and amoxicillin versus relevant comparator pharmaceutical products in South Africa and India.

PubMed

Reddy, Nallagundla H S; Patnala, Srinivas; Löbenberg, Raimar; Kanfer, Isadore

2014-10-01

Biowaivers are recommended for immediate-release solid oral dosage forms using dissolution testing as a surrogate for in vivo bioequivalence studies. Several guidance are currently available (the World Health Organization (WHO), the US FDA, and the EMEA) where the conditions are described. In this study, definitions, criteria, and methodologies according to the WHO have been applied. The dissolution performances of immediate-release metronidazole, zidovudine, and amoxicillin products purchased in South African and Indian markets were compared to the relevant comparator pharmaceutical product (CPP)/reference product. The dissolution performances were studied using US Pharmacopeia (USP) apparatus 2 (paddle) set at 75 rpm in each of three dissolution media (pH1.2, 4.5, and 6.8). Concentrations of metronidazole, zidovudine, and amoxicillin in each dissolution media were determined by HPLC. Of the 11 metronidazole products tested, only 8 could be considered as very rapidly dissolving products as defined by the WHO, whereas 2 of those products could be considered as rapidly dissolving products but did not comply with the f 2 acceptance criteria in pH 6.8. All 11 zidovudine products were very rapidly dissolving, whereas in the case of the 14 amoxicillin products tested, none of those products met any of the WHO criteria. This study indicates that not all generic products containing the same biopharmaceutics classification system (BCS) I drug and in similar strength and dosage form are necessarily in vitro equivalent. Hence, there is a need for ongoing market surveillance to determine whether marketed generic products containing BCS I drugs meet the release requirements to confirm their in vitro bioequivalence to the respective reference product.

Comparison of Dissolution Similarity Assessment Methods for Products with Large Variations: f2 Statistics and Model-Independent Multivariate Confidence Region Procedure for Dissolution Profiles of Multiple Oral Products.

PubMed

Yoshida, Hiroyuki; Shibata, Hiroko; Izutsu, Ken-Ichi; Goda, Yukihiro

2017-01-01

The current Japanese Ministry of Health Labour and Welfare (MHLW)'s Guideline for Bioequivalence Studies of Generic Products uses averaged dissolution rates for the assessment of dissolution similarity between test and reference formulations. This study clarifies how the application of model-independent multivariate confidence region procedure (Method B), described in the European Medical Agency and U.S. Food and Drug Administration guidelines, affects similarity outcomes obtained empirically from dissolution profiles with large variations in individual dissolution rates. Sixty-one datasets of dissolution profiles for immediate release, oral generic, and corresponding innovator products that showed large variation in individual dissolution rates in generic products were assessed on their similarity by using the f 2 statistics defined in the MHLW guidelines (MHLW f 2 method) and two different Method B procedures, including a bootstrap method applied with f 2 statistics (BS method) and a multivariate analysis method using the Mahalanobis distance (MV method). The MHLW f 2 and BS methods provided similar dissolution similarities between reference and generic products. Although a small difference in the similarity assessment may be due to the decrease in the lower confidence interval for expected f 2 values derived from the large variation in individual dissolution rates, the MV method provided results different from those obtained through MHLW f 2 and BS methods. Analysis of actual dissolution data for products with large individual variations would provide valuable information towards an enhanced understanding of these methods and their possible incorporation in the MHLW guidelines.

Model of dissolution in the framework of tissue engineering and drug delivery.

PubMed

Sanz-Herrera, J A; Soria, L; Reina-Romo, E; Torres, Y; Boccaccini, A R

2018-05-22

Dissolution phenomena are ubiquitously present in biomaterials in many different fields. Despite the advantages of simulation-based design of biomaterials in medical applications, additional efforts are needed to derive reliable models which describe the process of dissolution. A phenomenologically based model, available for simulation of dissolution in biomaterials, is introduced in this paper. The model turns into a set of reaction-diffusion equations implemented in a finite element numerical framework. First, a parametric analysis is conducted in order to explore the role of model parameters on the overall dissolution process. Then, the model is calibrated and validated versus a straightforward but rigorous experimental setup. Results show that the mathematical model macroscopically reproduces the main physicochemical phenomena that take place in the tests, corroborating its usefulness for design of biomaterials in the tissue engineering and drug delivery research areas.

DISSOLUTION OF PLUTONIUM METAL IN 8-10 M NITRIC ACID

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

Rudisill, T.; Pierce, R.

2012-02-21

The H-Canyon facility will be used to dissolve Pu metal for subsequent purification and conversion to plutonium dioxide (PuO{sub 2}) using Phase II of HB-Line. To support the new mission, the development of a Pu metal dissolution flowsheet which utilizes concentrated (8-10 M) nitric acid (HNO{sub 3}) solutions containing potassium fluoride (KF) is required. Dissolution of Pu metal in concentrated HNO{sub 3} is desired to eliminate the need to adjust the solution acidity prior to purification by anion exchange. The preferred flowsheet would use 8-10 M HNO{sub 3}, 0.015-0.07 M KF, and 0.5-1.0 g/L Gd to dissolve the Pu upmore » to 6.75 g/L. An alternate flowsheet would use 8-10 M HNO{sub 3}, 0.1-0.2 M KF, and 1-2 g/L B to dissolve the Pu. The targeted average Pu metal dissolution rate is 20 mg/min-cm{sup 2}, which is sufficient to dissolve a 'standard' 2250-g Pu metal button in 24 h. Plutonium metal dissolution rate measurements showed that if Gd is used as the nuclear poison, the optimum dissolution conditions occur in 10 M HNO{sub 3}, 0.04-0.05 M KF, and 0.5-1.0 g/L Gd at 112 to 116 C (boiling). These conditions will result in an estimated Pu metal dissolution rate of {approx}11-15 mg/min-cm{sup 2} and will result in dissolution times of 36-48 h for standard buttons. The recommended minimum and maximum KF concentrations are 0.03 M and 0.07 M, respectively. The maximum KF concentration is dictated by a potential room-temperature Pu-Gd-F precipitation issue at low Pu concentrations. The purpose of the experimental work described in this report was two-fold. Initially a series of screening experiments was performed to measure the dissolution rate of Pu metal as functions of the HNO{sub 3}, KF, and Gd or B concentrations. The objective of the screening tests was to propose optimized conditions for subsequent flowsheet demonstration tests. Based on the rate measurements, this study found that optimal dissolution conditions in solutions containing 0.5-1.0 g/L Gd occurred in 8-10 M HNO{sub 3} with 0.04-0.05 M KF at 112 to 116 C (boiling). The testing also showed that solutions containing 8-10 M HNO{sub 3}, 0.1-0.2 M KF, and 1-2 g/L B achieved acceptable dissolution rates in the same temperature range. To confirm that conditions identified by the dissolution rate measurements for solutions containing Gd or B can be used to dissolve Pu metal up to 6.75 g/L in the presence of Fe, demonstration experiments were performed using concentrations in the optimal ranges. In two of the demonstration experiments using Gd and in one experiment using B, the offgas generation during the dissolution was measured and samples were analyzed for H{sub 2}. The experimental methods used to perform the dissolution rate measurements and flowsheet demonstrations and a discussion of the results are presented.« less

Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.

PubMed

Hofmann, A F; Amelsberg, A; Esch, O; Schteingart, C D; Lyche, K; Jinich, H; Vansonnenberg, E; D'Agostino, H B

1997-06-01

Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure.

Dissolution properties of co-amorphous drug-amino acid formulations in buffer and biorelevant media.

PubMed

Heikkinen, A T; DeClerck, L; Löbmann, K; Grohganz, H; Rades, T; Laitinen, R

2015-07-01

Co-amorphous formulations, particularly binary drug-amino acid mixtures, have been shown to provide enhanced dissolution for poorly-soluble drugs and improved physical stability of the amorphous state. However, to date the dissolution properties (mainly intrinsic dissolution rate) of the co-amorphous formulations have been tested only in buffers and their supersaturation ability remain unexplored. Consequently, dissolution studies in simulated intestinal fluids need to be conducted in order to better evaluate the potential of these systems in increasing the oral bioavailability of biopharmaceutics classification system class II drugs. In this study, solubility and dissolution properties of the co-amorphous simvastatin-lysine, gibenclamide-serine, glibenclamide-threonine and glibenclamide-serine-threonine were studied in phosphate buffer pH 7.2 and biorelevant media (fasted and fed state simulated intestinal fluids (FaSSIF and FeSSIF, respectively)). The co-amorphous formulations were found to provide a long-lasting supersaturation and improve the dissolution of the drugs compared to the crystalline and amorphous drugs alone in buffer. Similar improvement, but in lesser extent, was observed in biorelevant media suggesting that a dissolution advantage observed in aqueous buffers may overestimate the advantage in vivo. However, the results show that, in addition to stability advantage shown earlier, co-amorphous drug-amino acid formulations provide dissolution advantage over crystalline drugs in both aqueous and biorelevant conditions.

Dissolution curve comparisons through the F(2) parameter, a Bayesian extension of the f(2) statistic.

PubMed

Novick, Steven; Shen, Yan; Yang, Harry; Peterson, John; LeBlond, Dave; Altan, Stan

2015-01-01

Dissolution (or in vitro release) studies constitute an important aspect of pharmaceutical drug development. One important use of such studies is for justifying a biowaiver for post-approval changes which requires establishing equivalence between the new and old product. We propose a statistically rigorous modeling approach for this purpose based on the estimation of what we refer to as the F2 parameter, an extension of the commonly used f2 statistic. A Bayesian test procedure is proposed in relation to a set of composite hypotheses that capture the similarity requirement on the absolute mean differences between test and reference dissolution profiles. Several examples are provided to illustrate the application. Results of our simulation study comparing the performance of f2 and the proposed method show that our Bayesian approach is comparable to or in many cases superior to the f2 statistic as a decision rule. Further useful extensions of the method, such as the use of continuous-time dissolution modeling, are considered.

Development of a Physiologically Relevant Population Pharmacokinetic in Vitro-in Vivo Correlation Approach for Designing Extended-Release Oral Dosage Formulation.

PubMed

Kim, Tae Hwan; Shin, Soyoung; Bulitta, Jürgen B; Youn, Yu Seok; Yoo, Sun Dong; Shin, Beom Soo

2017-01-03

Establishing a level A in vitro-in vivo correlation (IVIVC) for a drug with complex absorption kinetics is challenging. The objective of the present study was to develop an IVIVC approach based on population pharmacokinetic (POP-PK) modeling that incorporated physiologically relevant absorption kinetics. To prepare three extended release (ER) tablets of loxoprofen, three types of hydroxypropyl methylcellulose (HPMC 100, 4000, and 15000 cps) were used as drug release modifiers, while lactose and magnesium stearate were used as the diluent and lubricant, respectively. An in vitro dissolution test in various pH conditions showed that loxoprofen dissolution was faster at higher pH. The in vivo pharmacokinetics of loxoprofen was assessed following oral administration of the different loxoprofen formulations to Beagle dogs (n = 22 in total). Secondary peaks or shoulders were observed in many of the individual plasma concentration vs time profiles after ER tablet administration, which may result from secondary absorption in the intestine due to a dissolution rate increase under intestinal pH compared to that observed at stomach pH. In addition, in vivo oral bioavailability was found to decrease with prolonged drug dissolution, indicating site-specific absorption. Based on the in vitro dissolution and in vivo absorption data, a POP-PK IVIVC model was developed using S-ADAPT software. pH-dependent biphasic dissolution kinetics, described using modified Michaelis-Menten kinetics with varying V max , and site-specific absorption, modeled using a changeable absorbed fraction parameter, were applied to the POP-PK IVIVC model. To experimentally determine the biphasic dissolution profiles of the ER tablets, another in vitro dissolution test was conducted by switching dissolution medium pH based on an in vivo estimate of gastric emptying time. The model estimated, using linear regression, that in vivo initial maximum dissolution rate (V max (0) in vivo ) was highly correlated (r 2 > 0.998) with in vitro (V max (0) in vitro ), indicating that in vivo dissolution profiles obtained from POP-PK modeling could be converted to in vitro dissolution profiles and vice versa. Monte Carlo simulations were performed for model validation, and prediction errors for C max and AUC were all within the acceptable range (90 to 110%) according to the FDA guidelines. The developed model was successfully applied for the prediction of in vivo pharmacokinetics of a loxoprofen double-layered tablet using the in vitro dissolution profile. In conclusion, a level A IVIVC approach was developed and validated using population modeling that accounted for pH-dependent dissolution and site-specific absorption. Excellent correlations were observed between in vitro and in vivo dissolution profiles. This new approach holds great promise for the establishment of IVIVCs for drug and formulation development where absorption kinetics strongly depend on complex physiologically absorption processes.

Positive current collector for Li||Sb-Pb liquid metal battery

NASA Astrophysics Data System (ADS)

Ouchi, Takanari; Sadoway, Donald R.

2017-07-01

Corrosion in grid-scale energy storage devices adversely affects service lifetime and thus has a significant economic impact on their deployment. In this work, we investigate the corrosion of steel and stainless steels (SSs) as positive current collectors in the Li||Sb-Pb liquid metal battery. The erosion and formation of new phases on low-carbon steel, SS301, and SS430 were evaluated both in static conditions and under cell operating conditions. The cell performance is not adversely affected by the dissolution of iron or chromium but rather nickel. Furthermore, the in situ formation of a Fe-Cr-Sb layer helps mitigate the recession of SS430.

[Effect of Food Thickeners on the Disintegration, Dissolution, and Drug Activity of Rapid Oral-disintegrating Tablets].

PubMed

Tomita, Takashi; Kohda, Yukinao; Kudo, Kenzo

2018-01-01

　For patients with dysphagia in medical facilities and nursing homes, food thickeners are routinely used to aid the ingestion of medicines such as tablets. However, some types of thickeners affect the disintegration and dissolution of tablets, such as rapidly-disintegrating magnesium oxide tablets and donepezil hydrochloride orally disintegrating tablets. Additionally, delayed disintegration and dissolution of tablets affect a drug's efficacy. As an example, with Voglibose orally disintegrating tablets, marked differences are observed in changes in glucose levels during glucose tolerance testing. When using food thickeners to aid tablet ingestion, it is therefore necessary to select a product that has little effect on drug disintegration, dissolution, and activity.

Indentation-flexure and low-velocity impact damage in graphite/epoxy laminates

NASA Technical Reports Server (NTRS)

Kwon, Young S.; Sankar, Bhavani V.

1992-01-01

Static indentation and low velocity impact tests were performed on quasi-isotropic and cross ply graphite/epoxy composite laminates. The load deflection relations in static tests and impact force history in the impact tests were recorded. The damage was assessed by using ultrasonic C-scanning and photomicrographic techniques. The static behavior of the laminates and damage progression during loading, unloading, and reloading were explained by a simple plate delamination model. A good correlation existed between the static and impact responses. It was found that results from a few static indentation-flexture tests can be used to predict the response and damage in composite laminates due to a class of low velocity impact events.

Space Shuttle Flight Support Motor no. 1 (FSM-1)

NASA Technical Reports Server (NTRS)

Hughes, Phil D.

1990-01-01

Space Shuttle Flight Support Motor No. 1 (FSM-1) was static test fired on 15 Aug. 1990 at the Thiokol Corporation Static Test Bay T-24. FSM-1 was a full-scale, full-duration static test fire of a redesigned solid rocket motor. FSM-1 was the first of seven flight support motors which will be static test fired. The Flight Support Motor program validates components, materials, and manufacturing processes. In addition, FSM-1 was the full-scale motor for qualification of Western Electrochemical Corporation ammonium perchlorate. This motor was subjected to all controls and documentation requirements CTP-0171, Revision A. Inspection and instrumentation data indicate that the FSM-1 static test firing was successful. The ambient temperature during the test was 87 F and the propellant mean bulk temperature was 82 F. Ballistics performance values were within the specified requirements. The overall performance of the FSM-1 components and test equipment was nominal.

Bioequivalence and in vitro antimicrobial activity between generic and brand-name levofloxacin.

PubMed

Sun, Hsin-Yun; Liao, Hsiao-Wei; Sheng, Meng-Huei; Tai, Hui-Min; Kuo, Ching-Hua; Sheng, Wang-Huei

2016-07-01

Generic agents play a crucial role in reducing the cost of medical care in many countries. However, the therapeutic equivalence remains a great concern. Our study aims to assess the in vitro antimicrobial activity and bioequivalence between generic and brand-name levofloxacin. Enantiomeric purity test, dissolution test, and in vitro antimicrobial susceptibility against seven clinically important pathogens by the agar dilution method were employed to assess the similarity between four generic products and brand-name levofloxacin (Daiichi Sankyo). All the generic and brand-name levofloxacin passed enantiomeric purity test. The results of dissolution tests were not similar among the generic products and the brand-name levofloxacin. Compared with the generic products, the brand-name levofloxacin had the smallest mean variations (-25% to 13%) with reference standard (United States Pharmacopeia levofloxacin Reference Standards). Variations were observed particularly in dissolution profiles and in vitro activity between generic products and brand-name levofloxacin. Copyright © 2016 Elsevier Inc. All rights reserved.

Dissolution Studies of Papaverine Hydrochloride from Tablets in Three Pharmacopoeia Apparatuses.

PubMed

Polski, Andrzej; Kasperek, Regina; Rogowska, Magdalena; Iwaniak, Karol; Sobòtka-Polska, Karolina; Poleszak, Ewa

2015-01-01

In tablet production, the most important aspects are the physical properties of the tablets and their dissolution studies, which can be performed in four pharmacopoeial apparatuses. There are differences between them in construction and action, so differences in the results obtained are possible. The aim of the study was to compare the release of a model drug substance (papaverine hydrochloride) from tablets in three pharmacopoeial dissolution apparatus: a basket, a paddle (closed system) and flow-through cell (open system). The one series of tablets were produced by direct compression in a tablet press. The physical properties of the tablets (weight and size uniformity test, friability and hardness tests, disintegration time test), drug content and the release study of papaverine hydrochloride from tablets were studied in three dissolution apparatuses. The content of the active substance was studied spectrophotometrically. All tablets met the pharmacopoeic requirements. Over 80% of the model substance released from the tablets after 14 min in flow through the cell apparatus, while in the basket and paddle apparatuses after about 7 min 30 sec. After 20 min, the amount of the substance released in all apparatuses was over 90%. The release profiles of the drug substance in paddle and basket apparatuses were similar, while in the flow-through cell apparatus it was slightly slower. When the study conditions and composition of the tablets are the same, the release profile of the drug can be affected by the type of dissolution apparatus.

Brokenhearts: Dissolution of Romantic Relationships.

ERIC Educational Resources Information Center

Meeker, F. B.; La Fong, Carl

Results of an investigation examining the dissolution of romantic relationships are analyzed. Men and women (N=105) who had ended romantic relationships were surveyed in structured individual interviews. Commonalities and differences in respondents' perceptions of the experience were examined. Specific tests were made of a corollary to Waller's…

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2013 CFR

2013-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2014 CFR

2014-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2012 CFR

2012-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

21 CFR 343.90 - Dissolution and drug release testing.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Aspirin capsules. Aspirin capsules must meet the dissolution standard for aspirin capsules as contained in the United States Pharmacopeia (USP) 23 at page 132. (c) Aspirin delayed-release capsules and aspirin delayed-release tablets. Aspirin delayed-release capsules and aspirin delayed-release tablets must meet...

LLNL small-scale static spark machine: static spark sensitivity test

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

Foltz, M F; Simpson, L R

1999-08-23

Small-scale safety testing of explosives and other energetic materials is done in order to determine their sensitivity to various stimuli, such as friction, static spark, and impact. Typically this testing is done to discover potential handling problems that may exist for either newly synthesized materials of unknown behavior, or materials that have been stored for long periods of time. This report describes the existing ''Static Spark Test Apparatus'' at Lawrence Livermore National Laboratory (LLNL), as well as the method used to evaluate the relative static spark sensitivity of energetic materials. The basic design, originally developed by the Picatinny Arsenal inmore » New Jersey, is discussed. The accumulated data for the materials tested to date is not included here, with the exception of specific examples that have yielded interesting or unusual results during the tests.« less

Technical Evaluation Motor No. 7 (TEM-07)

NASA Technical Reports Server (NTRS)

Hugh, Phil

1991-01-01

Technical Evaluation Motor Number 7 (TEM-7) was a full scale, full-duration static test firing of a high performance motor (HPM) configuration solid rocket motor (SRM) with nozzle vectoring. The static test fire occurred on 11 December 1990 at the Thiokol Corporation Static Test Bay T-97. Documented here are the procedures, performance, and results available through 22 January 1991. Critical post test hardware activities and assessment of the test data are not complete. A completed test report will be submitted 60 days after the test date. Included here is a presentation and discussion of the TEM-7 performance, anomalies, and test result concurrence with the objectives outlined in CTP-0107 Revision A, Space Shuttle Technical Evaluation Motor number 7 (TEM-07) Static Fire Test Plan.

24. "GAFFTC 29 SEP 60, F106B STATIC TEST 1." Test ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

24. "G-AFFTC 29 SEP 60, F-106B STATIC TEST 1." Test of the Convair sled escape system at static test site east of Station "50". File no. 11,988-60. - Edwards Air Force Base, South Base Sled Track, Edwards Air Force Base, North of Avenue B, between 100th & 140th Streets East, Lancaster, Los Angeles County, CA

Interactions between a poorly soluble cationic drug and sodium dodecyl sulfate in dissolution medium and their impact on in vitro dissolution behavior.

PubMed

Huang, Zongyun; Parikh, Shuchi; Fish, William P

2018-01-15

In the pharmaceutical industry, in vitro dissolution testing ofsolid oral dosage forms is a very important tool for drug development and quality control. However, ion-pairing interaction between the ionic drugand surfactants in dissolution medium often occurs, resulting in inconsistent and incomplete drug release. The aim of this study is toevaluate the effects ofsodium dodecyl sulfate (SDS) mediated medium onthe dissolution behaviors of a poorly soluble cationic drug (Drug B). The study was carried out by measuring solubility of Drug B substance and dissolution rate of Drug B product in media containing SDS.Desolubilization of Drug B substance was observed at pH 4.5 in the presence of SDS at concentrations below critical micelle concentration (CMC) which is attributed to the formation of an insoluble di-dodecyl sulfate salt between SDS and Drug B. This ion-pairing effect is less significant with increasing medium pH where Drug B is less ionized and CMC of SDS is lower. In medium at pH 4.5, dissolution of Drug B product was found incomplete with SDS concentration below CMC due to the desolubilization of Drug B substance. In media with SDS level above CMC, the dissolution rate is rather slower with higher inter-vessel variations compared to that obtained in pH 4.5 medium without SDS. The dissolution results demonstrate that the presence of SDS in medium generates unexpected irregular dissolution profiles for Drug B which are attributed to incompatible dissolution medium for this particular drug. Therefore, non-ionic surfactant was selected for Drug B product dissolution method and ion-pairing effect in SDS mediated medium should be evaluated when developing a dissolution method for any poorly soluble cationic drugs. Copyright © 2017 Elsevier B.V. All rights reserved.

Flight evaluation of an engine static pressure noseprobe in an F-15 airplane

NASA Technical Reports Server (NTRS)

Foote, C. H.; Jaekel, R. F.

1981-01-01

The flight testing of an inlet static pressure probe and instrumented inlet case produced results consistent with sea-level and altitude stand testing. The F-15 flight test verified the basic relationship of total to static pressure ratio versus corrected airflow and automatic distortion downmatch with the engine pressure ratio control mode. Additionally, the backup control inlet case statics demonstrated sufficient accuracy for backup control fuel flow scheduling, and the station 6 manifolded production probe was in agreement with the flight test station 6 tota pressure probes.

Effect of Food Thickener on Dissolution and Laxative Activity of Magnesium Oxide Tablets in Mice.

PubMed

Tomita, Takashi; Goto, Hidekazu; Yoshimura, Yuya; Kato, Kazushige; Yoshida, Tadashi; Tanaka, Katsuya; Sumiya, Kenji; Kohda, Yukinao

2016-01-01

The present study examined the dissolution of magnesium oxide (MgO) from MgO tablets placed in a food thickening agent (food thickener) and its effects on laxative activity. We prepared mixtures of MgO tablets suspended in an aqueous suspension and food thickeners in order to evaluate the dissolution of MgO. The results of the dissolution tests revealed that agar-based food thickeners did not affect the MgO dissolution. In contrast, some xanthan gum-based food-thickener products show dissolution rates with certain mixtures containing disintegrated MgO tablets suspended in a food thickener that decrease over time. However, other xanthan gum-based food-thickener products show dissolution rates that decrease immediately after mixing, regardless of the time they were allowed to stand. In order to investigate the laxative activity of MgO, we orally administered a mixture of MgO suspension and food thickener to mice and observed their bowel movements. The animal experiments showed that when agar-based food thickeners were used, the laxative activity of MgO was not affected, but it decreased when xanthan gum-based food thickeners were used.

How does natural groundwater flow affect CO2 dissolution in saline aquifers?

NASA Astrophysics Data System (ADS)

Rosenzweig, R.; Michel-Meyer, I.; Tsinober, A.; Shavit, U.

2017-12-01

The dissolution of supercritical CO2 in aquifer brine is one of the most important trapping mechanisms in CO2 geological storage. Diffusion-limited dissolution is a very slow process. However, since the CO2-rich water is slightly denser than the CO2-free water, when CO2-free water is overlaid by heavier CO2-rich water, convective instability results in fingers of dense CO2-rich water that propagate downwards, causing CO2-unsaturated water to move upwards. This convection process significantly accelerates the dissolution rate of CO2 into the aquifer water.Most previous works have neglected the effect of natural groundwater flow and assumed it has no effect on the dissolution dynamics. However, it was found that in some of the saline aquifers groundwater flow rate, although small, is not zero. In this research, we study the effect of groundwater flow on dissolution by performing laboratory experiments in a bead pack cell using a mixture of methanol and ethylene-glycol as a CO2 analog while varying the water horizontal flow rate. We find that water horizontal flow decreases the number of fingers, their wavelength and their propagation velocity. When testing high water flow rates, no fingers were developed and the dissolution process was entirely diffusive. The effect of water flow on the dissolution rate did not show a clear picture. When increasing the horizontal flow rate the convective dissolution flux slightly decreased and then increased again. It seems that the combination of density-driven flow, water horizontal flow, mechanical dispersion and molecular diffusion affect the dissolution rate in a complex and non-monotonic manner. These intriguing dynamics should be further studied to understand their effect on dissolution trapping.

Influence of Concentration and Agitation of Sodium Hypochlorite and Peracetic Acid Solutions on Tissue Dissolution.

PubMed

Tanomaru-Filho, Mário; Silveira, Bruna Ramos Franco; Martelo, Roberta Bosso; Guerreiro-Tanomaru, Juliane Maria

2015-11-01

To evaluated the tissue dissolution of sodium hypochlorite (NaOCl) and peracetic acid (PA) solutions at different concentrations, with or without ultrasonic agitation. The following solutions were analyzed: 2.5% NaOCl, 0.5, 1 and 2% PA, 1% PA associated with 6.5% hydrogen peroxide (HP) and saline. Fragments of bovine pulp tissue with 25 ± 2g mg were immersed into test tubes containing 4 mL of the solutions for 10 minutes. In the groups with agitation, pulp tissues were submitted to 2 cycles of 1 minute of ultrasonic agitation. The specimens were weighed after the removal from the solutions. The percentage of mass loss was calculated according to the difference of mass before and after exposure to solutions. Data were submitted to ANOVA and Tukey tests (p < 0.05). A total of 2.5% NaOCl with or without agitation showed the higher tissue dissolution (between 64.5 and 67% of mass reduction) (p < 0.005). By comparing the PA solutions, the concentrations of 1 and 2% with or without agitation and the concentration of 0.5% with agitation showed similar dissolution activity (between 35.4 and 44% of mass reduction). The use of the ultrasonic agitation promoted an increase of the dissolution ability only for 0.5% PA. Peracetic acid solution has pulp tissue dissolution. However, this ability is lower than 2.5% NaOCl solution. The sodium hypochlorite solution shows higher ability to dissolve tissue than PA.

Dissolution and Separation of Aluminum and Aluminosilicates

DOE PAGES

McFarlane, Joanna; Benker, Dennis; DePaoli, David W.; ...

2015-12-19

The selection of an aluminum alloy for target irradiation affects post-irradiation target dissolution and separations. Recent tests with aluminum alloy 6061 yielded greater than expected precipitation in the dissolver, forming up to 10 wt.% solids of aluminum hydroxides and aluminosilicates. Aluminosilicate dissolution presents challenges in a number of different areas, metals extraction from minerals, flyash treatment, and separations from aluminum alloys. We present experimental work that attempts to maximize dissolution of aluminum metal, along with silicon, magnesium, and copper impurities, through control of temperature, the rate of reagent addition, and incubation time. Aluminum phase transformations have been identified as amore » function of time and temperature, using X-ray diffraction. Solutions have been analyzed using wet chemical methods and X-ray fluorescence. Our data have been compared with published calculations of aluminum phase diagrams. Approaches are given to enhance the dissolution of aluminum and aluminosilicate phases in caustic solution.« less

Influence of enzymes and surfactants on the disintegration behavior of cross-linked hard gelatin capsules during dissolution.

PubMed

Pennings, F H; Kwee, B L S; Vromans, H

2006-01-01

Gelatin exhibits cross-linking upon storage at stress conditions. Capsules stored at these conditions fail to show appropriate in vitro dissolution. The aim of this study is to show the effect of surfactants in the medium on the disintegration of the gelatin capsule. This is demonstrated in the presence and absence of the enzymes pancreatin and pepsin, the function of which is to improve the dissolution. Sodium lauryl sulfate (SLS) and Tween 80 are tested as surfactants. When SLS is used in the medium, dissolution is significantly hampered due to the formation of a less soluble precipitate of gelatin. Compared to SLS, Tween 80 shows far better disintegration and solubility results in dissolution media with neutral or low pH. Therefore, it is concluded in this study that Tween 80 is preferred when a surfactant is necessary to comply with sink condition requirements.

Continuous wavelet transforms for the simultaneous quantitative analysis and dissolution testing of lamivudine-zidovudine tablets.

PubMed

Dinç, Erdal; Özdemir, Nurten; Üstündağ, Özgür; Tilkan, Müşerref Günseli

2013-01-01

Dissolution testing has a very vital importance for a quality control test and prediction of the in vivo behavior of the oral dosage formulation. This requires the use of a powerful analytical method to get reliable, accurate and precise results for the dissolution experiments. In this context, new signal processing approaches, continuous wavelet transforms (CWTs) were improved for the simultaneous quantitative estimation and dissolution testing of lamivudine (LAM) and zidovudine (ZID) in a tablet dosage form. The CWT approaches are based on the application of the continuous wavelet functions to the absorption spectra-data vectors of LAM and ZID in the wavelet domain. After applying many wavelet functions, the families consisting of Mexican hat wavelet with the scaling factor a=256, Symlets wavelet with the scaling factor a=512 and the order of 5 and Daubechies wavelet at the scale factor a=450 and the order of 10 were found to be suitable for the quantitative determination of the mentioned drugs. These wavelet applications were named as mexh-CWT, sym5-CWT and db10-CWT methods. Calibration graphs for LAM and ZID in the working range of 2.0-50.0 µg/mL and 2.0-60.0 µg/mL were obtained measuring the mexh-CWT, sym5-CWT and db10-CWT amplitudes at the wavelength points corresponding to zero crossing points. The validity and applicability of the improved mexh-CWT, sym5-CWT and db10-CWT approaches was carried out by the analysis of the synthetic mixtures containing the analyzed drugs. Simultaneous determination of LAM and ZID in tablets was accomplished by the proposed CWT methods and their dissolution profiles were graphically explored.

Adolescent Sexuality and the Risk of Marital Dissolution

ERIC Educational Resources Information Center

Paik, Anthony

2011-01-01

This research investigates whether first sexual intercourse during adolescence is associated with increased risk of first marriage dissolution and tests whether the results are consistent with causal or selection explanations. Drawing on a sample of 3,793 ever-married women from the 2002 National Survey of Family Growth, this study estimated…

22. STATIC TEST TOWER VIEW OF TEST CELLS AND F1 ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

22. STATIC TEST TOWER VIEW OF TEST CELLS AND F-1 TEST LOCK DOWN FOR ENGINE. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

Evaluation of Relationship between Trunk Muscle Endurance and Static Balance in Male Students

PubMed Central

Barati, Amirhossein; SafarCherati, Afsaneh; Aghayari, Azar; Azizi, Faeze; Abbasi, Hamed

2013-01-01

Purpose Fatigue of trunk muscle contributes to spinal instability over strenuous and prolonged physical tasks and therefore may lead to injury, however from a performance perspective, relation between endurance efficient core muscles and optimal balance control has not been well-known. The purpose of this study was to examine the relationship of trunk muscle endurance and static balance. Methods Fifty male students inhabitant of Tehran university dormitory (age 23.9±2.4, height 173.0±4.5 weight 70.7±6.3) took part in the study. Trunk muscle endurance was assessed using Sørensen test of trunk extensor endurance, trunk flexor endurance test, side bridge endurance test and static balance was measured using single-limb stance test. A multiple linear regression analysis was applied to test if the trunk muscle endurance measures significantly predicted the static balance. Results There were positive correlations between static balance level and trunk flexor, extensor and lateral endurance measures (Pearson correlation test, r=0.80 and P<0.001; r=0.71 and P<0.001; r=0.84 and P<0.001, respectively). According to multiple regression analysis for variables predicting static balance, the linear combination of trunk muscle endurance measures was significantly related to the static balance (F (3,46) = 66.60, P<0.001). Endurance of trunk flexor, extensor and lateral muscles were significantly associated with the static balance level. The regression model which included these factors had the sample multiple correlation coefficient of 0.902, indicating that approximately 81% of the variance of the static balance is explained by the model. Conclusion There is a significant relationship between trunk muscle endurance and static balance. PMID:24800004

8. STATIC TEST TOWER NORTHWEST ELEVATION FROM THE POWER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

8. STATIC TEST TOWER - NORTHWEST ELEVATION FROM THE POWER PLANT TEST STAND. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

Accelerated Leach Testing of GLASS (ALTGLASS): I. Informatics approach to high level waste glass gel formation and aging

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

Jantzen, Carol M.; Trivelpiece, Cory L.; Crawford, Charles L.

Glass corrosion data from the ALTGLASS™ database were used to determine if gel compositions, which evolve as glass systems corrode, are correlated with the generation of zeolites and subsequent increase in the glass dissolution rate at long times. The gel compositions were estimated based on the difference between the elemental glass starting compositions and the measured elemental leachate concentrations from the long-term product consistency tests (ASTM C1285) at various stages of dissolution, ie, reaction progress. A well-characterized subset of high level waste glasses from the database was selected: these glasses had been leached for 15-20 years at reaction progresses upmore » to ~80%. The gel composition data, at various reaction progresses, were subjected to a step-wise regression, which demonstrated that hydrogel compositions with Si*/Al* ratios of <1.0 did not generate zeolites and maintained low dissolution rates for the duration of the experiments. Glasses that formed hydrogel compositions with Si^*/Al^* ratios ≥1, generated zeolites accompanied by a resumption in the glass dissolution rate. Finally, the role of the gel Si/Al ratio, and the interactions with the leachate, provides the fundamental understanding needed to predict if and when the glass dissolution rate will increase due to zeolitization.« less

Enhanced dissolution of sildenafil citrate as dry foam tablets.

PubMed

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

2017-01-30

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

Accelerated Leach Testing of GLASS (ALTGLASS): I. Informatics approach to high level waste glass gel formation and aging

DOE PAGES

Jantzen, Carol M.; Trivelpiece, Cory L.; Crawford, Charles L.; ...

2017-02-18

Glass corrosion data from the ALTGLASS™ database were used to determine if gel compositions, which evolve as glass systems corrode, are correlated with the generation of zeolites and subsequent increase in the glass dissolution rate at long times. The gel compositions were estimated based on the difference between the elemental glass starting compositions and the measured elemental leachate concentrations from the long-term product consistency tests (ASTM C1285) at various stages of dissolution, ie, reaction progress. A well-characterized subset of high level waste glasses from the database was selected: these glasses had been leached for 15-20 years at reaction progresses upmore » to ~80%. The gel composition data, at various reaction progresses, were subjected to a step-wise regression, which demonstrated that hydrogel compositions with Si*/Al* ratios of <1.0 did not generate zeolites and maintained low dissolution rates for the duration of the experiments. Glasses that formed hydrogel compositions with Si^*/Al^* ratios ≥1, generated zeolites accompanied by a resumption in the glass dissolution rate. Finally, the role of the gel Si/Al ratio, and the interactions with the leachate, provides the fundamental understanding needed to predict if and when the glass dissolution rate will increase due to zeolitization.« less

Preparation and Characterization of Liquisolid Compacts for Improved Dissolution of Telmisartan

PubMed Central

Narra, Nataraj; Rama Rao, Tadikonda

2014-01-01

The objective of the present work was to obtain pH independent and improved dissolution profile for a poorly soluble drug, telmisartan using liquisolid compacts. Liquisolid compacts were prepared using Transcutol HP as vehicle, Avicel PH102 as carrier, and Aerosil 200 as a coating material. The formulations were evaluated for drug excipient interactions, change in crystallinity of drug, flow properties, and general quality control tests of tablets using Fourier transform infrared (FTIR) spectroscopy, differential scanning calorimetry (DSC), X-ray diffraction (XRD), angle of repose, and various pharmacopoeial tests. In vitro dissolution studies were performed at three pH conditions (1.2, 4.5 and 7.4). Stability studies were performed at 40°C and 75% RH for three months. The formulation was found to comply with Indian pharmacopoeial limits for tablets. FTIR studies confirmed no interaction between drug and excipients. XRD and DSC studies indicate change/reduction in crystallinity of drug. Dissolution media were selected based on the solubility studies. The optimized formulation showed pH independent release profile with significant improvement (P < 0.005) in dissolution compared to plain drug and conventional marketed formulation. No significant difference was seen in the tablet properties, and drug release profile after storage for 3 months. PMID:25371826

Multicomponent amorphous nanofibers electrospun from hot aqueous solutions of a poorly soluble drug.

PubMed

Yu, Deng-Guang; Gao, Li-Dong; White, Kenneth; Branford-White, Christopher; Lu, Wei-Yue; Zhu, Li-Min

2010-11-01

To design and fabricate multicomponent amorphous electrospun nanofibers for synergistically improving the dissolution rate and permeation profiles of poorly water-soluble drugs. Nanofibers were designed to be composed of a poorly water soluble drug, helicid, a hydrophilic polymer polyvinylpyrrolidone as filament-forming matrix, sodium dodecyl sulfate as transmembrane enhancer and mannitol as taste masking agent, and were prepared from hot aqueous co-dissolving solutions of them. An elevated temperature electrospinning process was developed to fabricate the composite nanofibers, which were characterized using FESEM, DSC, XRD, ATR-FTIR, in vitro dissolution and permeation tests. The composite nanofibers were homogeneous with smooth surfaces and uniform structure, and the components were combined together in an amorphous state because of the favorable interactions such as hydrogen bonding, electrostatic interaction and hydrophobic interactions among them. In vitro dissolution and permeation tests demonstrated that the composite nanofibers had a dissolution rate over 26-fold faster than that of crude helicid particles and a 10-fold higher permeation rate across sublingual mucosa. A new type of amorphous material in the form of nanofibers was prepared from hot aqueous solutions of multiple ingredients using an electrospinning process. The amorphous nanofibers were able to improve the dissolution rate and permeation rate of helicid.

Static and Wind Tunnel Aero-Performance Tests of NASA AST Separate Flow Nozzle Noise Reduction Configurations

NASA Technical Reports Server (NTRS)

Mikkelsen, Kevin L.; McDonald, Timothy J.; Saiyed, Naseem (Technical Monitor)

2001-01-01

This report presents the results of cold flow model tests to determine the static and wind tunnel performance of several NASA AST separate flow nozzle noise reduction configurations. The tests were conducted by Aero Systems Engineering, Inc., for NASA Glenn Research Center. The tests were performed in the Channels 14 and 6 static thrust stands and the Channel 10 transonic wind tunnel at the FluiDyne Aerodynamics Laboratory in Plymouth, Minnesota. Facility checkout tests were made using standard ASME long-radius metering nozzles. These tests demonstrated facility data accuracy at flow conditions similar to the model tests. Channel 14 static tests reported here consisted of 21 ASME nozzle facility checkout tests and 57 static model performance tests (including 22 at no charge). Fan nozzle pressure ratio varied from 1.4 to 2.0, and fan to core total pressure ratio varied from 1.0 to 1.19. Core to fan total temperature ratio was 1.0. Channel 10 wind tunnel tests consisted of 15 tests at Mach number 0.28 and 31 tests at Mach 0.8. The sting was checked out statically in Channel 6 before the wind tunnel tests. In the Channel 6 facility, 12 ASME nozzle data points were taken and 7 model data points were taken. In the wind tunnel, fan nozzle pressure ratio varied from 1.73 to 2.8, and fan to core total pressure ratio varied from 1.0 to 1.19. Core to fan total temperature ratio was 1.0. Test results include thrust coefficients, thrust vector angle, core and fan nozzle discharge coefficients, total pressure and temperature charging station profiles, and boat-tail static pressure distributions in the wind tunnel.

Residual strength and crack propagation tests on C-130 airplane center wings with service-imposed fatigue damage

NASA Technical Reports Server (NTRS)

Snider, H. L.; Reeder, F. L.; Dirkin, W. J.

1972-01-01

Fourteen C-130 airplane center wings, each containing service-imposed fatigue damage resulting from 4000 to 13,000 accumulated flight hours, were tested to determine their fatigue crack propagation and static residual strength characteristics. Eight wings were subjected to a two-step constant amplitude fatigue test prior to static testing. Cracks up to 30 inches long were generated in these tests. Residual static strengths of these wings ranged from 56 to 87 percent of limit load. The remaining six wings containing cracks up to 4 inches long were statically tested as received from field service. Residual static strengths of these wings ranged from 98 to 117 percent of limit load. Damage-tolerant structural design features such as fastener holes, stringers, doublers around door cutouts, and spanwise panel splices proved to be effective in retarding crack propagation.

Feasibility of Using Gluconolactone, Trehalose and Hydroxy-Propyl Gamma Cyclodextrin to Enhance Bendroflumethiazide Dissolution Using Lyophilisation and Physical Mixing Techniques.

PubMed

Saleh, Ashraf; McGarry, Kenneth; Chaw, Cheng Shu; Elkordy, Amal Ali

2018-02-01

Hydrophobic drugs are facing a major challenge in dissolution rate enhancement and solubility in aqueous solutions; therefore, a variety of methods have been used to improve dissolution rate and/or solubility of bendroflumethiazide as a model hydrophobic drug. In this study, two main methods (physical mixing and lyophilisation) were used with gluconolactone, hydroxyl propyl γ-ccyclodextrin, and trehalose to explore this challenge. Bendroflumethiazide, practically insoluble in water, was mixed with one of the three excipients gluconolactone, hydroxyl propyl γ-cyclodextrin, and trehalose in three different ratios 1:1, 1:2, 1:5. To the best of our knowledge, the dissolution of the drug has not been previously enhanced by using either these methods or any of the used excipients. Samples containing drug and each of the excipients were characterized via dissolution testing, Fourier Transform infra-red spectroscopy, differential scanning calorimetry, and scanning electron microscopy. The used methods showed a significant enhancement in dug dissolution rate; physical mixing significantly, p < 0.05, increased the percentage of the drug released with time; for example, bendroflumethiazide dissolution in distilled water was improved from less than 20% to 99.79% within 90 min for physically mixed drug-cyclodextrin 1:5. The lyophilisation process was enhanced and the drug dissolution rate and the highest drug dissolution was achieved for (drug-gluconolactone 1:1) with 98.98% drug release within 90 min. the physical mixing and freeze drying processes significantly increased the percentage of drug release with time.

Validation protocol of analytical procedures for quantification of drugs in polymeric systems for parenteral administration: dexamethasone phosphate disodium microparticles.

PubMed

Martín-Sabroso, Cristina; Tavares-Fernandes, Daniel Filipe; Espada-García, Juan Ignacio; Torres-Suárez, Ana Isabel

2013-12-15

In this work a protocol to validate analytical procedures for the quantification of drug substances formulated in polymeric systems that comprise both drug entrapped into the polymeric matrix (assay:content test) and drug released from the systems (assay:dissolution test) is developed. This protocol is applied to the validation two isocratic HPLC analytical procedures for the analysis of dexamethasone phosphate disodium microparticles for parenteral administration. Preparation of authentic samples and artificially "spiked" and "unspiked" samples is described. Specificity (ability to quantify dexamethasone phosphate disodium in presence of constituents of the dissolution medium and other microparticle constituents), linearity, accuracy and precision are evaluated, in the range from 10 to 50 μg mL(-1) in the assay:content test procedure and from 0.25 to 10 μg mL(-1) in the assay:dissolution test procedure. The robustness of the analytical method to extract drug from microparticles is also assessed. The validation protocol developed allows us to conclude that both analytical methods are suitable for their intended purpose, but the lack of proportionality of the assay:dissolution analytical method should be taken into account. The validation protocol designed in this work could be applied to the validation of any analytical procedure for the quantification of drugs formulated in controlled release polymeric microparticles. Copyright © 2013 Elsevier B.V. All rights reserved.

33 CFR 156.170 - Equipment tests and inspections.

Code of Federal Regulations, 2014 CFR

2014-07-01

... distort under static liquid pressure at least 11/2 times the maximum allowable working pressure; and (iv... static liquid pressure test is successfully completed in the presence of the COTP. The test medium is not... static liquid pressure at least 11/2 times the maximum allowable working pressure; and (5) Each item of...

33 CFR 156.170 - Equipment tests and inspections.

Code of Federal Regulations, 2012 CFR

2012-07-01

... distort under static liquid pressure at least 11/2 times the maximum allowable working pressure; and (iv... static liquid pressure test is successfully completed in the presence of the COTP. The test medium is not... static liquid pressure at least 11/2 times the maximum allowable working pressure; and (5) Each item of...

33 CFR 156.170 - Equipment tests and inspections.

Code of Federal Regulations, 2013 CFR

2013-07-01

... distort under static liquid pressure at least 11/2 times the maximum allowable working pressure; and (iv... static liquid pressure test is successfully completed in the presence of the COTP. The test medium is not... static liquid pressure at least 11/2 times the maximum allowable working pressure; and (5) Each item of...

20. UNCOVERED TEST CELL AT THE STATIC TEST TOWER ON ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. UNCOVERED TEST CELL AT THE STATIC TEST TOWER ON THE WEST SIDE WHERE F-1 ENGINE WAS TESTED. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

Equipment and Protocols for Quasi-Static and Dynamic Tests of Very-High-Strength Concrete (VHSC) and High-Strength High-Ductility Concrete (HSHDC)

DTIC Science & Technology

2016-08-01

quasi -static mechanical properties, deformation behavior, and damage mechanisms in HSHDC and compare the behavior with VHSC. 2. Develop experimental ...using the experimental setup described in Chapter 6. The quasi -static strain rate was approximately 10-4/s. All panels tested have nominal dimensions...ER D C TR -1 6- 13 Force Protection Basing; TeCD 1a Equipment and Protocols for Quasi -Static and Dynamic Tests of Very-High-Strength

Evaluation and selection of bio-relevant dissolution media for a poorly water-soluble new chemical entity.

PubMed

Tang, L; Khan, S U; Muhammad, N A

2001-11-01

The purpose of this work is to develop a bio-relevant dissolution method for formulation screening in order to select an enhanced bioavailable formulation for a poorly water-soluble drug. The methods used included a modified rotating disk apparatus for measuring intrinsic dissolution rate of the new chemical entity (NCE) and the USP dissolution method II for evaluating dissolution profiles of the drug in three different dosage forms. The in vitro dissolution results were compared with the in vivo bioavailability for selecting a bio-relevant medium. The results showed that the solubility of the NCE was proportional to the concentration of sodium lauryl sulfate (SLS) in the media. The apparent intrinsic dissolution rate of the NCE was linear to the rotational speed of the disk, which indicated that the dissolution of the drug is a diffusion-controlled mechanism. The apparent intrinsic dissolution rate was also linear to the surfactant concentration in the media, which was interpreted using the Noyes and Whitney Empirical Theory. Three formulations were studied in three different SLS media using the bulk drug as a reference. The dissolution results were compared with the corresponding bioavailability results in dogs. In the 1% SLS--sink conditions--the drug release from all the formulations was complete and the dissolution results were discriminative for the difference in particle size of the drug in the formulations. However, the data showed poor IVIV correlation. In the 0.5% SLS medium--non-sink conditions--the dissolution results showed the same rank order among the tested formulations as the bioavailability. The best IVIV correlation was obtained from the dissolution in 0.25% SLS medium, an over-saturated condition. The conclusions are: a surfactant medium increases the apparent intrinsic dissolution rate of the NCE linearly due to an increase in solubility. A low concentration of surfactant in the medium (0.25%) is more bio-relevant than higher concentrations of surfactant in the media for the poorly water-soluble drug. Creating sink conditions (based on bulk drug solubilities) by using a high concentration of a surfactant in the dissolution medium may not be a proper approach in developing a bio-relevant dissolution method for a poorly water-soluble drug.

Assessment of pharmaceutical quality of furosemide tablets from multinational markets.

PubMed

Qureshi, S A; McGilveray, I J

1998-11-01

This report describes results of a collaborative study in which samples of the 40-mg strength of furosemide tablets were evaluated following a common protocol based on British (BP), European (Ph. Eur.), and US Pharmacopoeial (USP) specifications. Several tests, including identification, uniformity of mass, and dissolution, were performed. In total, excluding Lasix lots, results for 162 lots obtained from 115 manufacturers or suppliers were submitted. Also, 23 laboratories identified and submitted data for 34 lots of Lasix products available in their countries. There were no reported abnormalities in the physical test requirements of the products analyzed. The summaries (n, mean, and 95% CI) of the assay results for the "standard sample" (a common sample), Lasix lots from participating countries, and for all other furosemide products, respectively, are as follows: 30, 99.8%, 96-104; 33, 100.0%, 94-106; and 162, 99.6, 94-105. About half (approximately 62%) of the reported uniformity of mass results based on tablet weights were in the range 150-175 mg/tablet. However, there appears to be notable variability in tablet weights that would result in significant differences in the ratios (0.14 to 0.40) of active ingredient to excipient. The reported disintegration times ranged from 0 (instantaneous) to 18 min, with most less than 1 min. The drug dissolution testing was conducted with phosphate buffer at pH 5.8 (USP recommended). Another test was conducted with acetate buffer at pH 4.6 (noncompendial). There appears to be remarkable similarity in overall percentage of drug release from the three types of products (standard sample, Lasix lots, and other products). Although apparently there is a very wide spread in dissolution characteristics of the products tested, the analyses of variance did not detect differences among the products tested and, to this extent, would not indicate differences in bioavailability characteristics for most of these products. It is observed that about 20-38% of the variability in dissolution testing is not product related (i.e., it is from the dissolution testing itself), while the remaining 62-80% variability is product related (manufacturing, formulation, etc). The results of this multinational collaborative study showed that most of the furosemide products available in different countries met the required pharmaceutical quality standards, including drug-release characteristics. Based on an extensive statistical analysis, the main concern from the study was that the high variability in drug dissolution testing would require wide tolerance standards (e.g., pharmacopoeial standards). This may result in lack of needed discriminating ability of the test in revealing the impacts of formulation and manufacturing changes on in vitro, and perhaps in vivo, drug-release characteristics.

Biopharmaceutical characterisation of ciprofloxacin-metallic ion interactions: comparative study into the effect of aluminium, calcium, zinc and iron on drug solubility and dissolution.

PubMed

Stojković, Aleksandra; Tajber, Lidia; Paluch, Krzysztof J; Djurić, Zorica; Parojčić, Jelena; Corrigan, Owen I

2014-03-01

Ciprofloxacin bioavailability may be reduced when ciprofloxacin is co-administered with metallic ion containing preparations. In our previous study, physicochemical interaction between ciprofloxacin and ferrous sulphate was successfully simulated in vitro. In the present work, comparative in vitro ciprofloxacin solubility and dissolution studies were performed in the reactive media containing aluminium hydroxide, calcium carbonate or zinc sulphate. Solid phases collected from the dissolution vessel with aluminium hydroxide, calcium carbonate and zinc sulphate were investigated for their properties. The results obtained indicate that different types of adducts may form and retard ciprofloxacin solubility and dissolution. In the case of aluminium, no phase changes were observed. The solid phase generated in the presence of calcium carbonate was identified as hydrated ciprofloxacin base. Similarly to iron, a new complex consistent with Zn(SO4)2(Cl)2(ciprofloxacin)2 × nH2O stoichiometry was generated in the presence of relatively high concentrations of ciprofloxacin hydrochloride and zinc sulphate, indicating that small volume dissolution experiments can be useful for biorelevant dissolution tests.

Evolution of a mini-scale biphasic dissolution model: Impact of model parameters on partitioning of dissolved API and modelling of in vivo-relevant kinetics.

PubMed

Locher, Kathrin; Borghardt, Jens M; Frank, Kerstin J; Kloft, Charlotte; Wagner, Karl G

2016-08-01

Biphasic dissolution models are proposed to have good predictive power for the in vivo absorption. The aim of this study was to improve our previously introduced mini-scale dissolution model to mimic in vivo situations more realistically and to increase the robustness of the experimental model. Six dissolved APIs (BCS II) were tested applying the improved mini-scale biphasic dissolution model (miBIdi-pH-II). The influence of experimental model parameters including various excipients, API concentrations, dual paddle and its rotation speed was investigated. The kinetics in the biphasic model was described applying a one- and four-compartment pharmacokinetic (PK) model. The improved biphasic dissolution model was robust related to differing APIs and excipient concentrations. The dual paddle guaranteed homogenous mixing in both phases; the optimal rotation speed was 25 and 75rpm for the aqueous and the octanol phase, respectively. A one-compartment PK model adequately characterised the data of fully dissolved APIs. A four-compartment PK model best quantified dissolution, precipitation, and partitioning also of undissolved amounts due to realistic pH profiles. The improved dissolution model is a powerful tool for investigating the interplay between dissolution, precipitation and partitioning of various poorly soluble APIs (BCS II). In vivo-relevant PK parameters could be estimated applying respective PK models. Copyright © 2016 Elsevier B.V. All rights reserved.

Effect of particle size on solubility, dissolution rate, and oral bioavailability: evaluation using coenzyme Q10 as naked nanocrystals

PubMed Central

Sun, Jiao; Wang, Fan; Sui, Yue; She, Zhennan; Zhai, Wenjun; Wang, Chunling; Deng, Yihui

2012-01-01

In this paper work, four naked nanocrystals (size range 80–700 nm) were prepared without any surfactant or polymer using the solvent/nonsolvent method. The effects of particle size on their solubility, dissolution, and oral bioavailability were investigated. Solubility and dissolution testing were performed in three types of dissolution medium, and the studies demonstrated that the equilibrium solubilities of coenzyme Q10 nanocrystals and bulk drugs were not affected by the dissolution media but the kinetic solubilities were. Kinetic solubility curves and changes in particle size distribution were determined and well explained by the proposed solubilization model for the nanocrystals and bulk drugs. The particle size effect on dissolution was clearly influenced by the diffusion coefficients of the various dissolution media, and the dissolution velocity of coenzyme Q10 increased as particle size decreased. The bioavailability of coenzyme Q10 after oral administration in beagle dogs was improved by reducing the particle size. For 700 nm nanocrystals, the AUC0–48 was 4.4-fold greater than that for the coarse suspensions, but a further decrease in particle size from 700 nm to 120 nm did not contribute to improvement in bioavailability until the particle size was reduced to 80 nm, when bioavailability was increased by 7.3-fold. PMID:23166438

18. STATIC TEST TOWER VIEW FROM REMOVABLE LEVEL DOWN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. STATIC TEST TOWER - VIEW FROM REMOVABLE LEVEL DOWN TOWARDS GANTRY CRANE AND THREE TEST CELLS. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

VIEW OF EAST TEST SITE FROM TOP OF STATIC TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

VIEW OF EAST TEST SITE FROM TOP OF STATIC TEST TOWER VIEW INCLUDES STRUCTURAL DYNAMICS TEST STAND COLD CALIBRATION TEST STAND AND COMPONENTS TEST LAB. - Marshall Space Flight Center, East Test Area, Dodd Road, Huntsville, Madison County, AL

Effect of somatosensory and neurofeedback training on balance in older healthy adults: a preliminary investigation.

PubMed

Azarpaikan, Atefeh; Taheri Torbati, Hamidreza

2017-10-23

The aim of this study was to assess the effectiveness of balance training with somatosensory and neurofeedback training on dynamic and static balance in healthy, elderly adults. The sample group consisted of 45 healthy adults randomly assigned to one of the three test groups: somatosensory, neurofeedback, and a control. Individualization of the balance program started with pre-tests for static and dynamic balances. Each group had 15- and 30-min training sessions. All groups were tested for static (postural stability) and dynamic balances (Berg Balance Scale) in acquisition and transfer tests (fall risk of stability and timed up and go). Improvements in static and dynamic balances were assessed by somatosensory and neurofeedback groups and then compared with the control group. Results indicated significant improvements in static and dynamic balances in both test groups in the acquisition test. Results revealed a significant improvement in the transfer test in the neurofeedback and somatosensory groups, in static and dynamic conditions, respectively. The findings suggest that these methods of balance training had a significant influence on balance. Both the methods are appropriate to prevent falling in adults. Neurofeedback training helped the participants to learn static balance, while somatosensory training was effective on dynamic balance learning. Further research is needed to assess the effects of longer and discontinuous stimulation with somatosensory and neurofeedback training on balance in elderly adults.

Evaluation of Geosynthetic-Reinforced Flexible Pavements using Static Plate Load Tests

DOT National Transportation Integrated Search

2010-01-01

This study focuses on the response of full-scale geogrid-reinforced flexible pavements to static surface loading. Specifically, static plate load (SPL) tests were performed on a low-volume, asphalt pavement frontage road in Eastern Arkansas, USA (the...

Spousal Dissimilarity, Race, and Marital Dissolution

ERIC Educational Resources Information Center

Clarkwest, Andrew

2007-01-01

I test the claims that spousal differences in ideational, behavioral, and other traits contribute to elevated rates of marital dissolution among African Americans. Using data from 3 waves of the National Survey of Families and Households (N = 5,424), I find that African American spouses experience high levels of dissimilarity in traits that may…

Premarital Cohabitation and Marital Dissolution: An Examination of Recent Marriages

ERIC Educational Resources Information Center

Manning, Wendy D.; Cohen, Jessica A.

2012-01-01

An ongoing question remains for family researchers: Why does a positive association between cohabitation and marital dissolution exist when one of the primary reasons to cohabit is to test relationship compatibility? Drawing on recently collected data from the 2006-2008 National Survey of Family Growth, the authors examined whether premarital…

Characterization and evaluation of miconazole salts and cocrystals for improved physicochemical properties.

PubMed

Tsutsumi, Shunichirou; Iida, Motoo; Tada, Norio; Kojima, Takashi; Ikeda, Yukihiro; Moriwaki, Toshiya; Higashi, Kenjirou; Moribe, Kunikazu; Yamamoto, Keiji

2011-12-15

Miconazole salts and cocrystals were studied to improve the physicochemical properties of miconazole. Maleate, hemifumarate, and hemisuccinate were prepared and characterized by powder X-ray diffractometry, differential scanning calorimetry, and single crystal X-ray diffractometry. The intrinsic dissolution rate and stability of each miconazole crystal form were compared to those of freebase and nitrate to evaluate the optimal crystal form. Crystal structure analysis indicated that maleate was a salt formed by proton transfer from the acid to the imidazole group of miconazole. Hemifumarate and hemisuccinate were determined to be cocrystals formed by hydrogen bonding between the acids and the base in their crystal lattices. Intrinsic dissolution tests showed that the formation of salts and cocrystals improved the dissolution rate of miconazole. Stability tests of preliminary formulations prepared with each crystal form indicated that maleate and hemifumarate were unstable at 80°C and generated a specific degraded product, i.e., a Michael adduct, between miconazole and the acids. Hemisuccinate had a superior intrinsic dissolution rate and stability, and is thus considered a promising crystal form of miconazole. Copyright © 2011 Elsevier B.V. All rights reserved.

Chemoinformetrical evaluation of dissolution property of indomethacin tablets by near-infrared spectroscopy.

PubMed

Otsuka, Makoto; Tanabe, Hideaki; Osaki, Kazuo; Otsuka, Kuniko; Ozaki, Yukihiro

2007-04-01

The purpose of this study was to use near-infrared spectrometry (NIR) with chemoinformetrics to predict the change of dissolution properties in indomethacin (IMC) tablets during the manufacturing process. A comparative evaluation of the dissolution properties of the tablets was performed by the diffused reflectance (DRNIR) and transmittance (TNIR) NIR spectroscopic methods. Various kinds of IMC tablets (200 mg) were obtained from a powder (20 mg of IMC, 18 mg of microcrystalline cellulose, 160 mg of lactose, and 2 mg of magnesium stearate) under various compression pressures (60-398 MPa). Dissolution tests were performed in phosphate buffer, and the time required for 75% dissolution (T75) and mean dissolution time (MDT) were calculated. DRNIR and TNIR spectra were recorded, and the both NIR spectra used to establish a calibration model for predicting the dissolution properties by principal component regression analysis (PCR). The T75 and MDT increased as the compression pressure increased, since tablet porosity decreased with increasing pressure. Intensity of the DRNIR spectra of the compressed tablets decreased as the compression pressure increased. However, the intensity of TNIR spectra increased along with the pressure. The calibration models used to evaluate the dissolution properties of tablets were established by using PCR based on both DRNIR and TNIR spectra of the tablets. The multiple correlation coefficients of the relationship between the actual and predictive T75 by the DRNIR and TNIR methods were 0.831 and 0.962, respectively. It is possible to predict the dissolution properties of pharmaceutical preparations using both DRNIR and TNIR chemoinformetric methods. The TNIR method was more accurate for predictions of the dissolution behavior of tablets than the DRNIR method. (c) 2007 Wiley-Liss, Inc.

Clinopyroxene dissolution in basaltic melt

NASA Astrophysics Data System (ADS)

Chen, Yang; Zhang, Youxue

2009-10-01

The history of magmatic systems may be inferred from reactions between mantle xenoliths and host basalt if the thermodynamics and kinetics of the reactions are quantified. To study diffusive and convective clinopyroxene dissolution in silicate melts, diffusive clinopyroxene dissolution experiments were conducted at 0.47-1.90 GPa and 1509-1790 K in a piston-cylinder apparatus. Clinopyroxene saturation is found to be roughly determined by MgO and CaO content. The effective binary diffusivities, DMgO and DCaO, and the interface melt saturation condition, C0MgO×C0CaO, are extracted from the experiments. DMgO and DCaO show Arrhenian dependence on temperature. The pressure dependence is small and not resolved within 0.47-1.90 GPa. C0MgO×C0CaO in the interface melt increases with increasing temperature, but decreases with increasing pressure. Convective clinopyroxene dissolution, where the convection is driven by the density difference between the crystal and melt, is modeled using the diffusivities and interface melt saturation condition. Previous studies showed that the convective dissolution rate depends on the thermodynamics, kinetics and fluid dynamics of the system. Comparing our results for clinopyroxene dissolution to results from a previous study on convective olivine dissolution shows that the kinetic and fluid dynamic aspects of the two minerals are quite similar. However, the thermodynamics of clinopyroxene dissolution depends more strongly on the degree of superheating and composition of the host melt than that of olivine dissolution. The models for clinopyroxene and olivine dissolution are tested against literature experiments on mineral-melt interaction. They are then applied to previously proposed reactions between Hawaii basalts and mantle minerals, mid-ocean ridge basalts and mantle minerals, and xenoliths digestion in a basalt at Kuandian, Northeast China.

Kinetics of dissolution of UO2 in nitric acid solutions: A multiparametric study of the non-catalysed reaction

NASA Astrophysics Data System (ADS)

Cordara, T.; Szenknect, S.; Claparede, L.; Podor, R.; Mesbah, A.; Lavalette, C.; Dacheux, N.

2017-12-01

UO2 pellets were prepared by densification of oxides obtained from the conversion of the oxalate precursor. Then characterized in order to perform a multiparametric study of the dissolution in nitric acid medium. In this frame, for each sample, the densification rate, the grain size and the specific surface area of the prepared pellets were determined prior to the final dissolution experiments. By varying the concentration of the nitric acid solution and temperature, three different and successive steps were identified during the dissolution. Under the less aggressive conditions considered, a first transient step corresponding to the dissolution of the most reactive phases was observed at the solid/solution interface. Then, for all the tested conditions, a steady state step was established during which the normalised dissolution rate was found to be constant. It was followed by a third step characterized by a strong and continuous increase of the normalised dissolution rate. The duration of the steady state, also called "induction period", was found to vary drastically as a function of the HNO3 concentration and temperature. However, independently of the conditions, this steady state step stopped at almost similar dissolved material weight loss and dissolved uranium concentration. During the induction period, no important evolution of the topology of the solid/liquid interface was evidenced authorizing the use of the starting reactive specific surface area to evaluate the normalised dissolution rates thus the chemical durability of the sintered pellets. From the multiparametric study of UO2 dissolution proposed, oxidation of U(IV) to U(VI) by nitrate ions at the solid/liquid interface constitutes the limiting step in the overall dissolution mechanism associated to this induction period.

Predicting dense nonaqueous phase liquid dissolution using a simplified source depletion model parameterized with partitioning tracers

NASA Astrophysics Data System (ADS)

Basu, Nandita B.; Fure, Adrian D.; Jawitz, James W.

2008-07-01

Simulations of nonpartitioning and partitioning tracer tests were used to parameterize the equilibrium stream tube model (ESM) that predicts the dissolution dynamics of dense nonaqueous phase liquids (DNAPLs) as a function of the Lagrangian properties of DNAPL source zones. Lagrangian, or stream-tube-based, approaches characterize source zones with as few as two trajectory-integrated parameters, in contrast to the potentially thousands of parameters required to describe the point-by-point variability in permeability and DNAPL in traditional Eulerian modeling approaches. The spill and subsequent dissolution of DNAPLs were simulated in two-dimensional domains having different hydrologic characteristics (variance of the log conductivity field = 0.2, 1, and 3) using the multiphase flow and transport simulator UTCHEM. Nonpartitioning and partitioning tracers were used to characterize the Lagrangian properties (travel time and trajectory-integrated DNAPL content statistics) of DNAPL source zones, which were in turn shown to be sufficient for accurate prediction of source dissolution behavior using the ESM throughout the relatively broad range of hydraulic conductivity variances tested here. The results were found to be relatively insensitive to travel time variability, suggesting that dissolution could be accurately predicted even if the travel time variance was only coarsely estimated. Estimation of the ESM parameters was also demonstrated using an approximate technique based on Eulerian data in the absence of tracer data; however, determining the minimum amount of such data required remains for future work. Finally, the stream tube model was shown to be a more unique predictor of dissolution behavior than approaches based on the ganglia-to-pool model for source zone characterization.

On-line monitoring of in-vitro oral bioaccessibility tests as front-end to liquid chromatography for determination of chlorogenic acid isomers in dietary supplements.

PubMed

Kremr, Daniel; Cocovi-Solberg, David J; Bajerová, Petra; Ventura, Karel; Miró, Manuel

2017-05-01

A novel fully automated in-vitro oral dissolution test assay as a front-end to liquid chromatography has been developed and validated for on-line chemical profiling and monitoring of temporal release profiles of three caffeoylquinic acid (CQA) isomers, namely, 3-CQA,4-CQA and 5-CQA, known as chlorogenic acids, in dietary supplements. Tangential-flow filtration is harnessed as a sample processing approach for on-line handling of CQA containing extracts of hard gelatin capsules and introduction of protein-free samples into the liquid chromatograph. Oral bioaccessibility/dissolution test assays were performed at 37.0±0.5°C as per US Pharmacopeia recommendations using pepsin with activity of ca. 749,000 USP units/L in 0.1mol/L HCl as the extraction medium and a paddle apparatus stirred at 50rpm. CQA release rates and steady-state dissolution conditions were determined accurately by fitting the chromatographic datasets, namely, the average cumulative concentrations of bioaccessible pools of every individual isomer monitored during 200min, with temporal resolutions of ≥10min, to a first-order dissolution kinetic model. Distinct solid-to-liquid phase ratios in the mimicry of physiological extraction conditions were assessed. Relative standard deviations for intra-day repeatability and inter-day intermediate precision of 5-CQA within the 5-40µg/mL concentration range were <3.4% and <5.5%, respectively. Trueness of the automatic flow method for determination of 5-CQA released from dietary supplements in gastric fluid surrogate was demonstrated by spike recoveries, spanning from 91.5-104.0%, upon completion of the dissolution process. The proposed hyphenated setup was resorted for evaluating potential differences in dissolution profiles and content of the three most abundant chlorogenic acid isomers in dietary supplements from varied manufacturers. Copyright © 2016 Elsevier B.V. All rights reserved.

VIEW OF EAST TEST SITE FROM TOP OF STATIC TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

VIEW OF EAST TEST SITE FROM TOP OF STATIC TEST TOWER VIEW INCLUDES POWER PLANT TEST STAND AND SATURN V TEST STAND IN THE WEST TEST AREA (FAR BACKGROUND). - Marshall Space Flight Center, East Test Area, Dodd Road, Huntsville, Madison County, AL

Characterization of Space Shuttle Reusable Rocket Motor Static Test Stand Thrust Measurements

NASA Technical Reports Server (NTRS)

Cook, Mart L.; Gruet, Laurent; Cash, Stephen F. (Technical Monitor)

2003-01-01

Space Shuttle Reusable Solid Rocket Motors (RSRM) are static tested at two ATK Thiokol Propulsion facilities in Utah, T-24 and T-97. The newer T-97 static test facility was recently upgraded to allow thrust measurement capability. All previous static test motor thrust measurements have been taken at T-24; data from these tests were used to characterize thrust parameters and requirement limits for flight motors. Validation of the new T-97 thrust measurement system is required prior to use for official RSRM performance assessments. Since thrust cannot be measured on RSRM flight motors, flight motor measured chamber pressure and a nominal thrust-to-pressure relationship (based on static test motor thrust and pressure measurements) are used to reconstruct flight motor performance. Historical static test and flight motor performance data are used in conjunction with production subscale test data to predict RSRM performance. The predicted motor performance is provided to support Space Shuttle trajectory and system loads analyses. Therefore, an accurate nominal thrust-to-pressure (F/P) relationship is critical for accurate RSRM flight motor performance and Space Shuttle analyses. Flight Support Motors (FSM) 7, 8, and 9 provided thrust data for the validation of the T-97 thrust measurement system. The T-97 thrust data were analyzed and compared to thrust previously measured at T-24 to verify measured thrust data and identify any test-stand bias. The T-97 FIP data were consistent and within the T-24 static test statistical family expectation. The FSMs 7-9 thrust data met all NASA contract requirements, and the test stand is now verified for future thrust measurements.

13. TOP OF STATIC TEST TOWER VIEW OF STEEL TRUSS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. TOP OF STATIC TEST TOWER VIEW OF STEEL TRUSS STRUCTURE AND OVERHEAD CRANE. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

Development of a Thin Gauge Metallic Seal for Gas Turbine Engine Applications to 1700 F

NASA Technical Reports Server (NTRS)

England, Raymond O.

2006-01-01

The goal of doubling thrust-to-weight ratio for gas turbine engines has placed significant demands on engine component materials. Operating temperatures for static seals in the transition duct and turbine sections for instance, may well reach 2000 F within the next ten years. At these temperatures conventional age-hardenable superalloys lose their high strength via overaging and eventual dissolution of the gamma precipitate, and are well above their oxidation stability limit. Conventional solid-solution-strengthened alloys offer metallurgical stability, but suffer from rapid oxidation and little useful load bearing strength. Ceramic materials can theoretically be used at these temperatures, but manufacturing processes are in the developmental stages.

Development of a Single-Crystal Fifth-Generation Nickel Superalloy

NASA Astrophysics Data System (ADS)

Petrushin, N. V.; Elyutin, E. S.; Visik, E. M.; Golynets, S. A.

2017-11-01

The chemical and phase compositions of a rhenium-ruthenium-containing fifth-generation VZhM8 nickel superalloy, which is intended for single-crystal turbine blades of an aviation engine, are calculated using computer simulation. VZhM8 alloy <001>, <011>, and <111> single crystals are fabricated. The microstructure, the γ/γ' misfit, the segregation coefficients of alloying elements, the dissolution temperature of the γ' phase, and the solidus and liquidus temperatures of the VZhM8 alloy single crystals in the as-cast state and after heat treatment are studied. The temperature-time dependences of the static elastic modulus, the short-term mechanical properties, and the long-term strength of the alloy single crystals are determined

A Static Burst Test for Composite Flywheel Rotors

NASA Astrophysics Data System (ADS)

Hartl, Stefan; Schulz, Alexander; Sima, Harald; Koch, Thomas; Kaltenbacher, Manfred

2016-06-01

High efficient and safe flywheels are an interesting technology for decentralized energy storage. To ensure all safety aspects, a static test method for a controlled initiation of a burst event for composite flywheel rotors is presented with nearly the same stress distribution as in the dynamic case, rotating with maximum speed. In addition to failure prediction using different maximum stress criteria and a safety factor, a set of tensile and compressive tests is carried out to identify the parameters of the used carbon fiber reinforced plastics (CFRP) material. The static finite element (FE) simulation results of the flywheel static burst test (FSBT) compare well to the quasistatic FE-simulation results of the flywheel rotor using inertia loads. Furthermore, it is demonstrated that the presented method is a very good controllable and observable possibility to test a high speed flywheel energy storage system (FESS) rotor in a static way. Thereby, a much more expensive and dangerous dynamic spin up test with possible uncertainties can be substituted.

Sodium sulfate - Deposition and dissolution of silica

NASA Technical Reports Server (NTRS)

Jacobson, Nathan S.

1989-01-01

The hot-corrosion process for SiO2-protected materials involves deposition of Na2SO4 and dissolution of the protective SiO2 scale. Dew points for Na2SO4 deposition are calculated as a function of pressure, sodium content, and sulfur content. Expected dissolution regimes for SiO2 are calculated as a function of Na2SO4 basicity. Controlled-condition burner-rig tests on quartz verify some of these predicted dissolution regimes. The basicity of Na2SO4 is not always a simple function of P(SO3). Electrochemical measurements of an (Na2O) show that carbon creates basic conditions in Na2SO4, which explains the extensive corrosion of SiO2-protected materials containing carbon, such as SiC.

Results of Characterization and Retrieval Testing on Tank 241-C-110 Heel Solids

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

Callaway, William S.

2013-09-30

Nine samples of heel solids from tank 241-C-110 were delivered to the 222-S Laboratory for characterization and dissolution testing. After being drained thoroughly, the sample solids were primarily white to light-brown with minor dark-colored inclusions. The maximum dimension of the majority of the solids was <2 mm; however, numerous pieces of aggregate, microcrystalline, and crystalline solids with maximum dimensions ranging from 5-70 mm were observed. In general, the larger pieces of aggregate solids were strongly cemented. Natrophosphate [Na{sub 7}F(PO{sub 4}){sub 2}°19H{sub 2}O] was the dominant solid phase identified in the heel solids. Results of chemical analyses suggested that 85-87 wt%more » of the heel solids were the fluoridephosphate double salt. The average bulk density measured for the heel solids was 1.689 g/mL; the reference density of natrophosphate is 1.71 g/mL. Dissolution tests on composite samples indicate that 94 to 97 wt% of the tank 241-C-110 heel solids can be retrieved by dissolution in water. Dissolution and recovery of the soluble components in 1 kg (0.59 L) of the heel solids required the addition of ≈9.5 kg (9.5 L) of water at 15 °C and ≈4.4 kg (4.45 L) of water at 45 °C. Calculations performed using the Environmental Simulation Program indicate that dissolution of the ≈0.86 kg of natrophosphate in each kilogram of the tank 241-C-110 heel solids would require ≈9.45 kg of water at 15 °C and ≈4.25 kg of water at 45 °C. The slightly larger quantities of water determined to be required to retrieve the soluble components in 1 kg of the heel solids are consistent with that required for the dissolution of solids composed mainly of natrophosphate with a major portion of the balance consisting of highly soluble sodium salts. At least 98% of the structural water, soluble phosphate, sodium, fluoride, nitrate, carbonate, nitrite, sulfate, oxalate, and chloride in the test composites was dissolved and recovered in the dissolution tests. Most of the {sup 99}Tc and {sup 137}Cs present in the initial heel solids composites was removed in the water dissolution tests. The estimated activities/weights of {sup 129}I, {sup 234}U, {sup 235}U, {sup 236}U, and {sup 238}U in the dry residual solids were <25% of the weights/activities in the initial composite solids. Gibbsite and nordstrandite [both Al(OH){sub 3}] were the major solid phases identified in the solids remaining after completion of the dissolution tests. Chemical analysis indicated that the residual solids may have contained up to 62 wt% Al(OH){sub 3}. Significant quantities of unidentified phosphate-, iron-, bismuth-, silicon-, and strontium- bearing species were also present in the residual solids. The reference density of gibbsite (and nordstrandite) is 2.42 g/mL. The measured density of the residual solids, 2.65 g/mL, would be a reasonable value for solids containing gibbsite as the major component with minor quantities of other, higher density solids. Sieve analysis indicated that 22.2 wt% of the residual solids were discrete particles >710 μm in size, and 77.8 wt% were particulates <710 μm in size. Light-scattering measurements suggested that nearly all of the <710-μm particulates with diameters >12 μm were weakly bound aggregates of particles with diameters <2 μm. The <710-μm residual solids settled very slowly when dispersed in reagent water. The physical appearance of a suspension containing ≈0.4 vol% of the solids in pure water changed very little over a period of 46.5 hours. It should be noted that the distribution of particle sizes in the residual solids and the observed settling behavior were both strongly influenced by the procedures followed in the dissolution tests.« less

Investigation of two pitot-static tubes at supersonic speeds

NASA Technical Reports Server (NTRS)

Hasel, Lowell E; Coletti, Donald E

1948-01-01

The results of tests at a Mach number of 1.94 of an ogives-nose cylindrical pitot-static tube and similar tests at Mach numbers of 1.93 and 1.62 of a service pitot-static tube to determine body static pressures and indicated Mach numbers are presented and discussed. The radial pressure distribution on the cylindrical bodies is compared with that calculated by an approximate theory.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules III. Effects of the dissolution condition on the release process.

PubMed

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

2006-08-01

In the pharmaceutical preparation of a controlled release drug, it is very important and necessary to understand the entire release properties. As the first step, the dissolution test under various conditions is selected for the in vitro test, and usually the results are analyzed following Drug Approval and Licensing Procedures. In this test, 3 time points for each release ratio, such as 0.2-0.4, 0.4-0.6, and over 0.7, respectively, should be selected in advance. These are analyzed as to whether their values are inside or outside the prescribed aims at each time point. This method is very simple and useful but the details of the release properties can not be clarified or confirmed. The validity of the dissolution test in analysis using a combination of the square-root time law and cube-root law equations to understand all the drug release properties was confirmed by comparing the simulated value with that measured in the previous papers. Dissolution tests under various conditions affecting drug release properties in the human body were then examined, and the results were analyzed by both methods to identify their strengths and weaknesses. Hereafter, the control of pharmaceutical preparation, the manufacturing process, and understanding the drug release properties will be more efficient. It is considered that analysis using the combination of the square-root time law and cube-root law equations is very useful and efficient. The accuracy of predicting drug release properties in the human body was improved and clarified.

37. VIEW LOOKING SOUTH AT THE STATIC TEST TOWER. THIS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. VIEW LOOKING SOUTH AT THE STATIC TEST TOWER. THIS VIEW SHOWS TWO MAJOR CHANGES TO THE STATIC TEST TOWER: THE ADDITION OF THE NASA LOGO TO THE FACADE AND THE ADDITION OF THE UPPER STAGES TO THE JUPITER MISSILE IN THE WEST POSITION ON THE TOWER TO REPRESENT THE JUNO II CONFIGURATION. 1961, PHOTOGRAPHER UNKNOWN, FRED ORDWAY COLLECTION, U. S. SPACE AND ROCKET CENTER, HUNTSVILLE, AL. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

24. CLOSEUP OF MOUNT FOR F1 ENGINE ON STATIC TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

24. CLOSE-UP OF MOUNT FOR F-1 ENGINE ON STATIC TEST TOWER WITH STRUCTURAL DYNAMICS TEST STAND IN DISTANCE. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

Comparative release studies on suppositories using the basket, paddle, dialysis tubing and flow-through cell methods I. Acetaminophen in a lipophilic base suppository.

PubMed

Hori, Seiichi; Kawada, Tsubasa; Kogure, Sanae; Yabu, Shinako; Mori, Kenji; Akimoto, Masayuki

2017-02-01

The release characteristics of lipophilic suppositories containing acetaminophen (AAP) were examined using four types of dissolution methods: the basket, paddle, dialysis tubing (DT) and flow-through cell (FTC) methods. The suitability of each apparatus for quality control in AAP compounded suppositories was evaluated using statistical procedures. More than 80% of the drug was released over 60 min in all the release methods studied, with the exception of the basket method. Reproducible and faster release was achieved using the paddle method at 100 and 200 rpm, whereas poor release occurred with the basket method. The mean dissolution time (MDT), maximum dissolved quantity of AAP at the end of the sampling time (Q) and dissolution efficiency (DE) were calculated by model-independent methods. The FTC method with a single chamber used in this study was also appreciable for AAP suppositories (Q of 100%, MDT of 71-91 min and DE of 75-80%). The DT apparatus is considered similar to the FTC apparatus from a quality control perspective for judging the release properties of lipophilic base suppositories containing AAP. However, even the single chamber FTC used in this study has potential as an in vitro drug release test for suppositories. The comparative dissolution method is expected to become one of the valuable tools for selecting an adequate dissolution test.

Effect of Four Commonly Used Dissolution Media Surfactants on Pancreatin Proteolytic Activity.

PubMed

Guncheva, Maya; Stippler, Erika

2017-05-01

Proteolytic enzymes are often used in dissolution testing of cross-linked gelatin capsules that do not conform to the dissolution specification. Their catalytic activity, however, can be affected when they are added to a dissolution media containing solubility enhancers, such as surfactants. The aim of this study was to assess the activity of pancreatic proteases in presence of four commonly used surfactants. We found that pancreatin exhibits remarkable proteolytic activity in the presence of Tween 80, even at the concentrations as high as 250 times its critical micelle concentration (cmc) in water, whereas, Triton X-100 enhanced the proteolytic activity of pancreatin when added at concentrations above its cmc in water. Both surfactants are non-ionic surfactants. On the other hand, sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB), which are ionic surfactants, have a detrimental effect on the proteolytic activity of pancreatin. For example, a 50% reduction of the pancreatin activity was found in samples which contain a minor amount of SDS (0.05% w/v) in comparison to a surfactant-free reaction. Additionally, no activity was observed for the pancreatin-SDS samples which were incubated for 30 min at 40°C prior to testing. CTAB had an impact on pancreatin activity at concentrations higher than its cmc. Data from this manuscript can be used as a benchmark for optimization of the dissolution procedures that require use of both surfactants and enzymes.

[Effect of stability and dissolution of realgar nano-particles using solid dispersion technology].

PubMed

Guo, Teng; Shi, Feng; Yang, Gang; Feng, Nian-Ping

2013-09-01

To improve the stability and dissolution of realgar nano-particles by solid dispersion. Using polyethylene glycol 6000 and poloxamer-188 as carriers, the solid dispersions were prepare by melting method. XRD, microscopic inspection were used to determine the status of realgar nano-particles in solid dispersions. The content and stability test of As(2)0(3) were determined by DDC-Ag method. Hydride generation atomic absorption spectrometry was used to determine the content of Arsenic and investigated the in vitro dissolution behavior of solid dispersions. The results of XRD and microscopic inspection showed that realgar nano-particles in solid dispersions were amorphous. The dissolution amount and rate of Arsenic from realgar nano-particles of all solid dispersions were increased significantly, the reunion of realgar nano-particles and content of As(2)0(3) were reduced for the formation of solid dispersions. The solid dispersion of realgar nano-particles with poloxamer-188 as carriers could obviously improve stability, dissolution and solubility.

Effect of Cr, Ti, V, and Zr Micro-additions on Microstructure and Mechanical Properties of the Al-Si-Cu-Mg Cast Alloy

NASA Astrophysics Data System (ADS)

Shaha, S. K.; Czerwinski, F.; Kasprzak, W.; Friedman, J.; Chen, D. L.

2016-05-01

Uniaxial static and cyclic tests were used to assess the role of Cr, Ti, V, and Zr additions on properties of the Al-7Si-1Cu-0.5Mg (wt pct) alloy in as-cast and T6 heat-treated conditions. The microstructure of the as-cast alloy consisted of α-Al, eutectic Si, and Cu-, Mg-, and Fe-rich phases Al2.1Cu, Al8.5Si2.4Cu, Al5.2CuMg4Si5.1, and Al14Si7.1FeMg3.3. In addition, the micro-sized Cr/Zr/Ti/V-rich phases Al10.7SiTi3.6, Al6.7Si1.2TiZr1.8, Al21.4Si3.4Ti4.7VZr1.8, Al18.5Si7.3Cr2.6V, Al7.9Si8.5Cr6.8V4.1Ti, Al6.3Si23.2FeCr9.2V1.6Ti1.3, Al92.2Si16.7Fe7.6Cr8.3V1.8, and Al8.2Si30.1Fe1.6Cr18.8V3.3Ti2.9Zr were present. During solution treatment, Cu-rich phases were completely dissolved, while the eutectic silicon, Fe-, and Cr/Zr/Ti/V-rich intermetallics experienced only partial dissolution. Micro-additions of Cr, Zr, Ti, and V positively affected the alloy strength. The modified alloy in the T6 temper during uniaxial tensile tests exhibited yield strength of 289 MPa and ultimate tensile strength of 342 MPa, being significantly higher than that for the Al-Si-Cu-Mg base. Besides, the cyclic yield stress of the modified alloy in the T6 state increased by 23 pct over that of the base alloy. The fatigue life of the modified alloy was substantially longer than that of the base alloy tested using the same parameters. The role of Cr, Ti, V, and Zr containing phases in controlling the alloy fracture during static and cyclic loading is discussed.

Carbonate Mineralization of Volcanic Province Basalts

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

Schaef, Herbert T.; McGrail, B. Peter; Owen, Antionette T.

2010-03-31

Flood basalts are receiving increasing attention as possible host formations for geologic sequestration of anthropogenic CO2, with studies underway in the United States, India, Iceland, and Canada. As an extension of our previous experiments with Columbia River basalt, basalts from the eastern United States, India, and South Africa were reacted with aqueous dissolved CO2 and aqueous dissolved CO2-H2S mixtures under supercritical CO2 (scCO2) conditions to study the geochemical reactions resulting from injection of CO2 in such formations. The results of these studies are consistent with cation release behavior measured in our previous experiments (in press) for basalt samples tested inmore » single pass flow through dissolution experiments under dilute solution and mildly acidic conditions. Despite the basalt samples having similar bulk chemistry, mineralogy and apparent dissolution kinetics, long-term static experiments show significant differences in rates of mineralization as well as compositions and morphologies of precipitates that form when the basalts are reacted with CO2-saturated water. For example, basalt from the Newark Basin in the United States was by far the most reactive of any basalt tested to date. Carbonate reaction products for the Newark Basin basalt were globular in form and contained significantly more Fe than the secondary carbonates that precipitated on the other basalt samples. In comparison, the post-reacted samples associated with the Columbia River basalts from the United States contained calcite grains with classic dogtooth spar morphology and trace cation substitution (Mg and Mn). Carbonation of the other basalts produced precipitates with compositions that varied chemically throughout the entire testing period. Examination of polished cross sections of the reacted grains by scanning electron microscopy and energy dispersive x-ray spectroscopy show precipitate overgrowths with varying chemical compositions. Compositional differences in the precipitates suggest changes in fluid chemistry unique to the dissolution behavior of each basalt sample reacted with CO2-saturated water. The Karoo basalt from South Africa appeared the least reactive, with very limited mineralization occurring during the testing with CO2-saturated water. The relative reactivity of different basalt samples were unexpectedly different in the experiments conducted using aqueous dissolved CO2-H2S mixtures versus those reacted with aqueous dissolved CO2 mixtures. For example, the Karoo basalt was highly reactive in the presence of aqueous dissolved CO2-H2S, as evident by small nodules of carbonate coating the basalt grains after 181 days of testing. However the most reactive basalt in CO2-H2O, Newark Basin, formed limited amounts of carbonate precipitates in the presence of aqueous dissolved CO2-H2S mixture. Basalt reactivity in CO2-H2O mixtures appears to be controlled by the composition of the glassy mesostasis, which is the most reactive component in the basalt rock. With the addition of H2S to the CO2-H2O system, basalt reactivity appears to be controlled by precipitation of coatings of insoluble Fe sulfides.« less

The effect of dentin on the pulp tissue dissolution capacity of sodium hypochlorite and calcium hydroxide.

PubMed

Slutzky-Goldberg, Iris; Hanut, Aiham; Matalon, Shlomo; Baev, Valery; Slutzky, Hagay

2013-08-01

Sodium hypochlorite (NaOCl) and calcium hydroxide (Ca[OH]2) have tissue dissolution capacity. The aim of this study was to evaluate the potential effect of dentin on their tissue dissolution capacity in a novel dentin model. Dentin models were prepared from 25 freshly extracted human molar teeth; the crowns were separated from the roots, and a rectangular inner shape was prepared. Pulp tissue samples adjusted to similar weights of 6.5 ± 0.2 mg were randomly divided into 6 groups: NaOCl groups in test tubes or dentin models for 1 hour, Ca(OH)2 groups in test tubes or dentin models for 1 week, and control groups saline in test tubes or dentin models for 1 week. The final weights after the experimental period were checked and compared with the initial weights. The differences were statistically analyzed. The tissue dissolution capacity of Ca(OH)2 was affected by the presence of dentin. Similarly, NaOCl lost its effect on the pulp tissue after incubation in dentin. Comparison between all test groups showed highly significant differences (P < .001). Dentin has a detrimental effect on the ability of NaOCl and Ca(OH)2 to dissolve pulp tissue. The dentin model appears to be an efficient tool for the study of interactions between local endodontic medicaments, dentin, and pulp tissue. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Dissolution Behaviour of Metal Elements from Several Types of E-waste Using Leaching Test

NASA Astrophysics Data System (ADS)

Nor, Nik Hisyamudin Muhd; Amira Nordin, Nurul; Mohamad, Fariza; Jaibee, Shafizan; Ismail, Al Emran; Omar, Badrul; Fauzi Ahmad, Mohd; Rahim, Abd Khalil Abd; Kamaruddin, Muhamad Khalif Ikhwan Mohd; Turan, Faiz Mohd; Abu Bakar, Elmi; Yokoyama, Seiji

2017-08-01

Rapid development of the electrical and electronic was increasing annually due to the demand by the human being. Increasing production of electrical and electronic product led to the increasing of electric and electronic waste or can be called as the e-waste. The UN Environment Programme estimates that the world generates 20-50 million tons of the e-waste each year and the amount is raising three times faster than other forms of municipal waste. This study is focusing on the investigation of the dissolution behaviour of metal element from several types of e-waste by hydrometallurgical process. Leaching test was conducted on the e-waste by using acid as the reagent solution. Prior to the leaching test, manual dismantling, separation, and crushing process were carried out to the e-waste. The e-waste were characterized by Scanning Electron Microcopy (SEM) and the Energy Dispersive X-ray Spectroscopy (EDX) to define the elements inside the sample of e-waste. While the liquid residue from leaching test was analyzed by using Inductively Couple Plasma-Mass Spectrometer (ICP-MS) to define the dissolution behaviour of the metal element that contain in the e-waste. It was found that the longest time for dismantling process was the dismantling of laptop. The dissolution behaviour of Fe, Al, Zn and Pb elements in the e-waste has affected to the increase of pH. The increasing pH led to the reduction of the metals element during leaching process.

Divorce and Adult Psychological Well-Being: Clarifying the Role of Gender and Child Age

ERIC Educational Resources Information Center

Williams, Kristi; Dunne-Bryant, Alexandra

2006-01-01

Substantial evidence indicates that marital dissolution has negative consequences for adult well-being. Because most research focuses on the average consequences of divorce, we know very little about factors that moderate this association. The present study tests the hypothesis that the effects of marital dissolution on adult well-being are…

Variations in Divorce Rates by Community Size: A Test of the Social Integration Explanation.

ERIC Educational Resources Information Center

Shelton, Beth Anne

1987-01-01

Found a strong correlation between residential mobility rate and a measure of marital dissolution. Concluded that community size and marital dissolution correlated positively because of higher levels of residential mobility in large cities and urban areas than in small cities and rural areas. Found high residential mobility both an indicator and a…

Using a Word Association Test for the Assessment of High School Students' Cognitive Structures on Dissolution

ERIC Educational Resources Information Center

Derman, Aysegul; Eilks, Ingo

2016-01-01

Understanding students' cognitive structures in a specific knowledge domain helps to determine the ''what, how and why'' features of such knowledge, so that we can take these structures into consideration in teaching. The purpose of the present study was to identify students' cognitive structures about solution and dissolution concepts. The study…

Students' Understanding of Salt Dissolution: Visualizing Animation in the Chemistry Classroom

NASA Astrophysics Data System (ADS)

Malkoc, Ummuhan

The present study explored the effect of animation implementation in learning a chemistry topic. 135 high school students taking chemistry class were selected for this study (quasi-experimental groups = 67 and control groups = 68). Independent samples t-tests were run to compare animation and control groups between and within the schools. The over-arching finding of this research indicated that when science teachers used animations while teaching salt dissolution phenomena, students will benefit the application of animations. In addition, the findings informed the TPACK framework on the idea that visual tools are important in students' understanding of salt dissolution concepts.

Dissolution of spent nuclear fuel in carbonate-peroxide solution

NASA Astrophysics Data System (ADS)

Soderquist, Chuck; Hanson, Brady

2010-01-01

This study shows that spent UO2 fuel can be completely dissolved in a room temperature carbonate-peroxide solution apparently without attacking the metallic Mo-Tc-Ru-Rh-Pd fission product phase. In parallel tests, identical samples of spent nuclear fuel were dissolved in nitric acid and in an ammonium carbonate, hydrogen peroxide solution. The resulting solutions were analyzed for strontium-90, technetium-99, cesium-137, europium-154, plutonium, and americium-241. The results were identical for all analytes except technetium, where the carbonate-peroxide dissolution had only about 25% of the technetium that the nitric acid dissolution had.

Controlled evaluation of silver nanoparticle dissolution using atomic force microscopy.

PubMed

Kent, Ronald D; Vikesland, Peter J

2012-07-03

Incorporation of silver nanoparticles (AgNPs) into an increasing number of consumer products has led to concern over the potential ecological impacts of their unintended release to the environment. Dissolution is an important environmental transformation that affects the form and concentration of AgNPs in natural waters; however, studies on AgNP dissolution kinetics are complicated by nanoparticle aggregation. Herein, nanosphere lithography (NSL) was used to fabricate uniform arrays of AgNPs immobilized on glass substrates. Nanoparticle immobilization enabled controlled evaluation of AgNP dissolution in an air-saturated phosphate buffer (pH 7.0, 25 °C) under variable NaCl concentrations in the absence of aggregation. Atomic force microscopy (AFM) was used to monitor changes in particle morphology and dissolution. Over the first day of exposure to ≥10 mM NaCl, the in-plane AgNP shape changed from triangular to circular, the sidewalls steepened, the in-plane radius decreased by 5-11 nm, and the height increased by 6-12 nm. Subsequently, particle height and in-plane radius decreased at a constant rate over a 2-week period. Dissolution rates varied linearly from 0.4 to 2.2 nm/d over the 10-550 mM NaCl concentration range tested. NaCl-catalyzed dissolution of AgNPs may play an important role in AgNP fate in saline waters and biological media. This study demonstrates the utility of NSL and AFM for the direct investigation of unaggregated AgNP dissolution.

Failure mechanics in low-velocity impacts on thin composite plates

NASA Technical Reports Server (NTRS)

Elber, W.

1983-01-01

Eight-ply quasi-isotropic composite plates of Thornel 300 graphite in Narmco 5208 epoxy resin (T300/5208) were tested to establish the degree of equivalence between low-velocity impact and static testing. Both the deformation and failure mechanics under impact were representable by static indentation tests. Under low-velocity impacts such as tool drops, the dominant deformation mode of the plates was the first, or static, mode. Higher modes are excited on contact, but they decay significantly by the time the first-mode load reaches a maximum. The delamination patterns were observed by X-ray analysis. The areas of maximum delamination patterns were observed by X-ray analysis. The areas of maximum delamination coincided with the areas of highest peel stresses. The extent of delamination was similar for static and impact tests. Fiber failure damage was established by tensile tests on small fiber bundles obtained by deplying test specimens. The onset of fiber damage was in internal plies near the lower surface of the plates. The distribution and amount of fiber damage was similar fo impact and static tests.

38. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

38. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST BAY AND EXHAUST PIT, LOOKING WEST - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

37. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

37. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF TEST BAY AND EXHAUST PIT, LOOKING SOUTHWEST - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

Iron dissolution of dust source materials during simulated acidic processing: the effect of sulfuric, acetic, and oxalic acids.

PubMed

Chen, Haihan; Grassian, Vicki H

2013-09-17

Atmospheric organic acids potentially display different capacities in iron (Fe) mobilization from atmospheric dust compared with inorganic acids, but few measurements have been made on this comparison. We report here a laboratory investigation of Fe mobilization of coal fly ash, a representative Fe-containing anthropogenic aerosol, and Arizona test dust, a reference source material for mineral dust, in pH 2 sulfuric acid, acetic acid, and oxalic acid, respectively. The effects of pH and solar radiation on Fe dissolution have also been explored. The relative capacities of these three acids in Fe dissolution are in the order of oxalic acid > sulfuric acid > acetic acid. Oxalate forms mononuclear bidentate ligand with surface Fe and promotes Fe dissolution to the greatest extent. Photolysis of Fe-oxalate complexes further enhances Fe dissolution with the concomitant degradation of oxalate. These results suggest that ligand-promoted dissolution of Fe may play a more significant role in mobilizing Fe from atmospheric dust compared with proton-assisted processing. The role of atmospheric organic acids should be taken into account in global-biogeochemical modeling to better access dissolved atmospheric Fe deposition flux at the ocean surface.

Estimating rock and slag wool fiber dissolution rate from composition.

PubMed

Eastes, W; Potter, R M; Hadley, J G

2000-12-01

A method was tested for calculating the dissolution rate constant in the lung for a wide variety of synthetic vitreous silicate fibers from the oxide composition in weight percent. It is based upon expressing the logarithm of the dissolution rate as a linear function of the composition and using a different set of coefficients for different types of fibers. The method was applied to 29 fiber compositions including rock and slag fibers as well as refractory ceramic and special-purpose, thin E-glass fibers and borosilicate glass fibers for which in vivo measurements have been carried out. These fibers had dissolution rates that ranged over a factor of about 400, and the calculated dissolution rates agreed with the in vivo values typically within a factor of 4. The method presented here is similar to one developed previously for borosilicate glass fibers that was accurate to a factor of 1.25. The present coefficients work over a much broader range of composition than the borosilicate ones but with less accuracy. The dissolution rate constant of a fiber may be used to estimate whether disease would occur in animal inhalation or intraperitoneal injection studies of that fiber.

Elevated CO2 affects shell dissolution rate but not calcification rate in a marine snail.

PubMed

Nienhuis, Sarah; Palmer, A Richard; Harley, Christopher D G

2010-08-22

As CO(2) levels increase in the atmosphere, so too do they in the sea. Although direct effects of moderately elevated CO(2) in sea water may be of little consequence, indirect effects may be profound. For example, lowered pH and calcium carbonate saturation states may influence both deposition and dissolution rates of mineralized skeletons in many marine organisms. The relative impact of elevated CO(2) on deposition and dissolution rates are not known for many large-bodied organisms. We therefore tested the effects of increased CO(2) levels--those forecast to occur in roughly 100 and 200 years--on both shell deposition rate and shell dissolution rate in a rocky intertidal snail, Nucella lamellosa. Shell weight gain per day in live snails decreased linearly with increasing CO(2) levels. However, this trend was paralleled by shell weight loss per day in empty shells, suggesting that these declines in shell weight gain observed in live snails were due to increased dissolution of existing shell material, rather than reduced production of new shell material. Ocean acidification may therefore have a greater effect on shell dissolution than on shell deposition, at least in temperate marine molluscs.

Technical Evaluation Motor no. 5 (TEM-5)

NASA Technical Reports Server (NTRS)

Cook, M.

1990-01-01

Technical Evaluation Motor No. 5 (TEM-5) was static test fired at the Thiokol Corporation Static Test Bay T-97. TEM-5 was a full scale, full duration static test fire of a high performance motor (HPM) configuration solid rocket motor (SRM). The primary purpose of TEM static tests is to recover SRM case and nozzle hardware for use in the redesigned solid rocket motor (RSRM) flight program. Inspection and instrumentation data indicate that the TEM-5 static test firing was successful. The ambient temperature during the test was 41 F and the propellant mean bulk temperature (PMBT) was 72 F. Ballistics performance values were within the specified requirements. The overall performance of the TEM-5 components and test equipment was nominal. Dissembly inspection revealed that joint putty was in contact with the inner groove of the inner primary seal of the ignitor adapter-to-forward dome (inner) joint gasket; this condition had not occurred on any previous static test motor or flight RSRM. While no qualification issues were addressed on TEM-5, two significant component changes were evaluated. Those changes were a new vented assembly process for the case-to-nozzle joint and the installation of two redesigned field joint protection systems. Performance of the vented case-to-nozzle joint assembly was successful, and the assembly/performance differences between the two field joint protection system (FJPS) configurations were compared.

In Vitro Dissolution as a Tool for Formulation Selection: Telmisartan Two-Step IVIVC.

PubMed

Ruiz Picazo, Alejandro; Martinez-Martinez, Ma Teresa; Colón-Useche, Sarin; Iriarte, Ramon; Sánchez-Dengra, Bárbara; González-Álvarez, Marta; García-Arieta, Alfredo; González-Álvarez, Isabel; Bermejo, Marival

2018-05-17

The purpose of this investigation was to develop an exploratory two-step level A IVIVC for three telmisartan oral immediate release formulations, the reference product Micardis, and two generic formulations (X1 and X2). Correlation was validated with a third test formulation, Y1. Experimental solubility and permeability data were obtained to confirm that telmisartan is a class II compound under the Biopharmaceutic Classification System. Bioequivalence (BE) studies plasma profiles were combined using a previously published reference scaling procedure. X2 demonstrated in vivo BE, while X1 and Y1 failed to show BE due to the lower boundary of the 90% confidence interval for C max being outside the acceptance limits. Average plasma profiles were deconvoluted by the Loo-Riegelman method to obtain the oral fractions absorbed ( f a ). Fractions dissolved ( f diss ) were obtained in several conditions in USP II and USP IV apparatus, and later, the results were compared in order to find the most biopredictive model, calculating the f 2 similarity factor. The apparatus and conditions showing the same rank order than in vivo data were selected for further refinement of conditions. A Levy plot was constructed to estimate the time scaling factor and to make both processes, dissolution and absorption, superimposable. The in vitro dissolution experiment that reflected more accurately the in vivo behavior of the different formulations of telmisartan employed the USP IV dissolution apparatus and a dissolution environment with a flow rate of 8 mL/min and a three-step pH change, from 1.2 to 4.5 and 6.8, with a 0.05% of Tween 80. Thus, these conditions gave rise to a biopredictive dissolution test. This new model is able to predict the formulation differences in dissolution that were previously observed in vivo, which could be used as a risk-analysis tool for formulation selection in future bioequivalence trials.

Some observations on loss of static strength due to fatigue cracks

NASA Technical Reports Server (NTRS)

Illg, Walter; Hardrath, Herbert F

1955-01-01

Static tensile tests were performed on simple notched specimens containing fatigue cracks. Four types of aluminum alloys were investigated: 2024-T3(formerly 24S-T3) and 7075-T6(formerly 75S-T6) in sheet form, and 2024-T4(formerly 24S-T4) and 7075-T6(formerly 75S-T6) in extruded form. The cracked specimens were tested statically under four conditions: unmodified and with reduced eccentricity of loading by three methods. Results of static tests on C-46 wings containing fatigue cracks are also reported.

Effect of iron on inhibition of acid demineralisation of bovine dental enamel in vitro.

PubMed

Buzalaf, Marília Afonso Rabelo; de Moraes Italiani, Flávia; Kato, Melissa Thiemi; Martinhon, Cleide Cristina Rodrigues; Magalhães, Ana Carolina

2006-10-01

Iron ions (Fe(2+)) have been shown to be cariostatic in many studies particularly by their ability to reduce bacterial metabolism. Nevertheless, the role of iron ions on dissolution of enamel is unexplored. The aim of the present study was therefore to investigate the protective effect of increasing concentrations (0-120mmol/L) of Fe(2+) on the dissolution of enamel. Enamel powder was subjected to acetic acid made with increasing concentrations with respect to FeSO(4)x7H(2)O. In order to determine the amount of enamel dissolved, the phosphate released in the medium was analysed spectrophotometrically using the Fiske-Subarrow method. Data were tested using Kruskall-Wall and Dunn's tests (p<0.05). The degree of protection was found to approach maximum at about 15mmol/L Fe(2+). Higher concentrations of Fe(2+) did not have an extra effect on inhibition of dissolution of enamel powder. In the next step, the protective effect of 15mmol/L Fe(2+) against mineral dissolution of the bovine enamel was evaluated using a simple abiotic model system. Enamel blocks were exposed to a sequence of seven plastic vials, each containing 1mL of 10mmol/L acetic acid. The acid in vial 4 was made 15mmol/L with respect to FeSO(4)x7H(2)O. The mineral dissolved during each challenge was thus determined by phosphate released as described above. Data were tested using two-way ANOVA (p<0.05). Lower demineralisation (around 45%) was found in vial 4 (with Fe) that continued stable until vial 7. Thus, our data suggest that Fe(2+) can be effective on inhibition of dissolution of enamel and that this effect may be durable.

Difference in the Dissolution Behaviors of Tablets Containing Polyvinylpolypyrrolidone (PVPP) Depending on Pharmaceutical Formulation After Storage Under High Temperature and Humid Conditions.

PubMed

Takekuma, Yoh; Ishizaka, Haruka; Sumi, Masato; Sato, Yuki; Sugawara, Mitsuru

Storage under high temperature and humid conditions has been reported to decrease the dissolution rate for some kinds of tablets containing polyvinylpolypyrrolidone (PVPP) as a disintegrant. The aim of this study was to elucidate the properties of pharmaceutical formulations with PVPP that cause a decrease in the dissolution rate after storage under high temperature and humid conditions by using model tablets with a simple composition. Model tablets, which consisted of rosuvastatin calcium or 5 simple structure compounds, salicylic acid, 2-aminodiphenylmethane, 2-aminobiphenyl, 2-(p-tolyl)benzoic acid or 4.4'-biphenol as principal agents, cellulose, lactose hydrate, PVPP and magnesium stearate as additives, were made by direct compression. The model tables were wrapped in paraffin papers and stored for 2 weeks at 40°C/75% relative humidity (RH). Dissolution tests were carried out by the paddle method in the Japanese Pharmacopoeia 16th edition. Model tablets with a simple composition were able to reproduce a decreased dissolution rate after storage at 40°C/75% RH. These tablets showed significantly decreased water absorption activities after storage. In the case of tablets without lactose hydrate by replacing with cellulose, a decreased dissolution rate was not observed. Carboxyl and amino groups in the structure of the principal agent were not directly involved in the decreased dissolution. 2-Benzylaniline tablets showed a remarkably decreased dissolution rate and 2-aminobiphenyl and 2-(p-tolyl)benzoic acid tablets showed slightly decreased dissolution rates, though 4,4'-biphenol tablets did not show a decrease dissolution rate. We demonstrated that additives and structure of the principal agent were involved in the decreased in dissolution rate for tablets with PVPP. The results suggested that one of the reasons for a decreased dissolution rate was the inclusion of lactose hydrate in tablets. The results also indicated that compounds as principal agents with low affinity for PVPP may be easily affected by airborne water under high temperature and humid conditions. This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page.

A novel microdialysis-dissolution/permeation system for testing oral dosage forms: A proof-of-concept study.

PubMed

Fong, Sophia Yui Kau; Poulsen, Jessie; Brandl, Martin; Bauer-Brandl, Annette

2017-01-01

A novel microdialysis-dissolution/permeation (M-D/P) system was developed for the biopharmaceutical assessment of oral drug formulations. This system consists of a side-by-side diffusion chamber, a microdialysis unit fixed within the dissolution chamber for continuous sampling, and a biomimetic Permeapad® as the intestinal barrier. In the M-D/P system, the concentration of the molecularly dissolved drug (with MWCO <20kDa) was measured over time in the dissolution compartment (representing the gastrointestinal tract) while the concentration of the permeated drug was measured in the acceptor compartment (representing the blood). The kinetics of both the dissolution process and the permeation process were simultaneously quantified under circumstances that mimic physiological conditions. For the current proof-of-concept study, hydrocortisone (HCS) in the form of slowly dissolving solvate crystals and buffer and the biorelevant fasted state simulated intestinal fluids (FaSSIF), were employed as the model drug and dissolution media, respectively. The applicability of the M-D/P system to dissolution and permeation profiling of HCS in buffer and in FaSSIF has been successfully demonstrated. Compared to the conventional direct sampling method (using filter of 0.1-0.45μm), sampling by the M-D/P system exhibited distinct advantages, including (1) showing minimal disturbance of the permeation process, (2) differentiating "molecularly" dissolved drugs from "apparently" dissolved drugs during dissolution of HCS in FaSSIF, and (3) being less laborious and having better sampling temporal resolution. M-D/P system appeared to be a promising, simple and routine tool that allows for the researchers' intensive comprehension of the interplay of dissolution and permeation thus helping for better oral formulation screening and as an ultimate goal, for better dosage forms assessment. Copyright © 2016. Published by Elsevier B.V.

In vitro dissolution of proton-pump inhibitor products intended for paediatric and geriatric use in physiological bicarbonate buffer.

PubMed

Liu, Fang; Shokrollahi, Honaz

2015-05-15

Proton-pump inhibitor (PPI) products based on enteric coated multiparticulates are design to meet the needs of patients who cannot swallow tablets such as children and older adults. Enteric coated PPI preparations exhibit delays in in vivo absorption and onset of antisecretory effects, which is not reflected by the rapid in vitro dissolution in compendial pH 6.8 phosphate buffer commonly used for assessment of these products. A more representative and physiological medium, pH 6.8 mHanks bicarbonate buffer, was used in this study to evaluate the in vitro dissolution of enteric coated multiparticulate-based PPI products. Commercially available omeprazole, lansoprazole and esomeprazole products were subject to dissolution tests using USP-II apparatus in pH 4.5 phosphate buffer saline for 45 min (acid stage) followed by pH 6.8 phosphate buffer or pH 6.8 mHanks bicarbonate buffer. In pH 6.8 phosphate buffer, all nine tested products displayed rapid and comparable dissolution profiles meeting the pharmacopeia requirements for delayed release preparations. In pH 6.8 mHanks buffer, drug release was delayed and failed the pharmacopeia requirements from most enteric coated preparations. Despite that the same enteric polymer, methacrylic acid-ethyl acrylate copolymer (1:1), was applied to all commercial multiparticulate-based products, marked differences were observed between dissolution profiles of these preparations. The use of pH 6.8 physiological bicarbonate (mHanks) buffer can serve as a useful tool to provide realistic and discriminative in vitro release assessment of enteric coated PPI preparations and to assist rational formulation development of these products. Copyright © 2015 Elsevier B.V. All rights reserved.

A novel dissolution method for evaluation of polysaccharide based colon specific delivery systems: A suitable alternative to animal sacrifice.

PubMed

Singh, Sachin Kumar; Yadav, Ankit Kumar; Prudhviraj, G; Gulati, Monica; Kaur, Puneet; Vaidya, Yogyata

2015-06-20

The most extensively used test for predicting in-vivo release kinetics of a drug from its orally administered dosage forms is dissolution testing. For polysaccharide based, colon targeted oral delivery systems, the entire path of the gut traversed by the dosage form needs to be simulated for assessing its in-vivo dissolution pattern. This includes the dissolution testing sequentially in simulated gastric fluid (SGF), simulated intestinal fluid (SIF) and simulated colonic fluid (SCF). For SGF and SIF, simple and standardized composition is well-known. However, preparation of SCF requires addition of either the colonic contents of rodents or human faecal slurry. A method is proposed, wherein a mixture of five probiotics cultured in the presence of a prebiotic under anaerobic conditions is able to surrogate the colonic fluid. Release profiles of drug from colon targeted delivery systems in this medium were studied and compared to those generated in the conventionally used media containing rodent caecal contents and human faecal slurry. The results from the three studies were found to be quite similar. These findings suggest that the proposed medium may prove to be useful not only as a biorelevant and discriminatory method but may also help in achieving the 3Rs objective regarding the ethical use of animals. Copyright © 2015 Elsevier B.V. All rights reserved.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

PubMed Central

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-01-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant. PMID:28368030

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation.

PubMed

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-03

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Co-grinding Effect on Crystalline Zaltoprofen with β-cyclodextrin/Cucurbit[7]uril in Tablet Formulation

NASA Astrophysics Data System (ADS)

Li, Shanshan; Lin, Xiang; Xu, Kailin; He, Jiawei; Yang, Hongqin; Li, Hui

2017-04-01

This work aimed to investigate the co-grinding effects of β-cyclodextrin (β-CD) and cucurbit[7]uril (CB[7]) on crystalline zaltoprofen (ZPF) in tablet formulation. Crystalline ZPF was prepared through anti-solvent recrystallization and fully analyzed through single-crystal X-ray diffraction. Co-ground dispersions and mono-ground ZPF were prepared using a ball grinding process. Results revealed that mono-ground ZPF slightly affected the solid state, solubility, and dissolution of crystalline ZPF. Co-ground dispersions exhibited completely amorphous states and elicited a significant reinforcing effect on drug solubility. UV-vis spectroscopy, XRPD, FT-IR, DSC, ssNMR, and molecular docking demonstrated the interactions in the amorphous product. Hardness tests on blank tablets with different β-CD and CB[7] contents suggested the addition of β-CD or CB[7] could enhance the compressibility of the powder mixture. Disintegration tests showed that CB[7] could efficiently shorten the disintegrating time. Dissolution tests indicated that β-CD and CB[7] could accelerate the drug dissolution rate via different mechanisms. Specifically, CB[7] could accelerate the dissolution rate by improving disintegration and β-CD showed a distinct advantage in solubility enhancement. Based on the comparative study on β-CD and CB[7] for tablet formulation combined with co-grinding, we found that CB[7] could be considered a promising drug delivery, which acted as a disintegrant.

Lurasidone-β-cyclodextrin complexes: Physicochemical characterization and comparison of their antidepressant, antipsychotic activities against that of self microemulsifying formulation

NASA Astrophysics Data System (ADS)

Londhe, Vaishali Y.; Deshmane, Aishwarya B.; Singh, Sarita R.; Kulkarni, Yogesh A.

2018-04-01

Lurasidone hydrochloride (LHD) is an atypical antipsychotic drug has poor aqueous solubility and low bioavailability (9-19%). This study describes effect of different methods of complex formation with β-cyclodextrin (BCD) on enhancement of dissolution and on antidepressant, antipsychotic effects of LHD. Other purpose of this study is to compare pharmacodynamic effects of complexes with that of self microemulsifying drug delivery system of LHD (SMEDDS). Inclusion complexes (IC) of LHD and BCD were prepared by physical mixing (PM), kneading (KN) and spray drying (SD) in a 1:1 M ratio. These complexes were characterized by different techniques. KN and SD showing enhancement in dissolution, were compared with SMEDDS using Forced swim test (FST) and Tail suspension test (TST) for antidepressant action and Paw test for antipsychotic activity. Characterization of complexes confirmed interaction between LHD and BCD. Enhancement in dissolution is seen in following order SD > KN > PM > LHD. In all three animal models, SD, KN and SMEDDS showed statistically significant effect (p < .05) than drug alone showing enhancement in bioavailability. Complexation of LHD with BCD enhances dissolution which reflected in improvement of antidepressant and antipsychotic activity of drug. Solubility enhancement methods like complexation and self microemulsion improves pharmacodynamic activities of drug. Improvement of pharmacodynamic effect is seen in order, SD ≥ SMEDDS ≥ KN > LHD.

Comparison of three preservation techniques for slowing dissolution of calcareous nannofossils in organic rich sediments

USGS Publications Warehouse

Seefelt, Ellen L.; Self-Trail, Jean; Schultz, Arthur P.

2015-01-01

In an attempt to halt or reduce dissolution of calcareous nannofossils in organic and/or pyrite-rich sediments, three different methods of short-term storage preservation were tested for efficacy: vacuum packing, argon gas replacement, and buffered water. Abundance counts of calcareous nannofossil assemblages over a six month period showed that none of the three preservation methods were consistently effective in reducing assemblage loss due to dissolution. In most cases, the control slides made at the drill site had more abundant calcareous nannofossil assemblages than those slides made from sediments stored via vacuum packing, argon gas replacement, or buffered water. Thin section and XRD analyses showed that in most cases, <1% pyrite was needed to drive the oxidation-reduction reaction that resulted in dissolution, even in carbonate-rich sediments.

In Vitro Dissolution Tests of Plutonium and Americium Containing Contamination Originating From ZPPR Fuel Plates

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

William F. Bauer; Brian K. Schuetz; Gary M. Huestis

2012-09-01

Assessing the extent of internal dose is of concern whenever workers are exposed to airborne radionuclides or other contaminants. Internal dose determinations depend upon a reasonable estimate of the expected biological half-life of the contaminants in the respiratory tract. One issue with refractory elements is determining the dissolution rate of the element. Actinides such as plutonium (Pu) and Americium (Am) tend to be very refractory and can have biological half-lives of tens of years. In the event of an exposure, the dissolution rates of the radionuclides of interest needs to be assessed in order to assign the proper internal dosemore » estimates. During the November 2011 incident at the Idaho National Laboratory (INL) involving a ZPPR fuel plate, air filters in a constant air monitor (CAM) and a giraffe filter apparatus captured airborne particulate matter. These filters were used in dissolution rate experiments to determine the apparent dissolution half-life of Pu and Am in simulated biological fluids. This report describes these experiments and the results. The dissolution rates were found to follow a three term exponential decay equation. Differences were noted depending upon the nature of the biological fluid simulant. Overall, greater than 95% of the Pu and 93% of the Am were in a very slow dissolving component with dissolution half-lives of over 10 years.« less

Pinaverium Bromide: Development and Validation of Spectrophotometric Methods for Assay and Dissolution Studies.

PubMed

Martins, Danielly da Fonte Carvalho; Florindo, Lorena Coimbra; Machado, Anna Karolina Mouzer da Silva; Todeschini, Vítor; Sangoi, Maximiliano da Silva

2017-11-01

This study presents the development and validation of UV spectrophotometric methods for the determination of pinaverium bromide (PB) in tablet assay and dissolution studies. The methods were satisfactorily validated according to International Conference on Harmonization guidelines. The response was linear (r2 > 0.99) in the concentration ranges of 2-14 μg/mL at 213 nm and 10-70 μg/mL at 243 nm. The LOD and LOQ were 0.39 and 1.31 μg/mL, respectively, at 213 nm. For the 243 nm method, the LOD and LOQ were 2.93 and 9.77 μg/mL, respectively. Precision was evaluated by RSD, and the obtained results were lower than 2%. Adequate accuracy was also obtained. The methods proved to be robust using a full factorial design evaluation. For PB dissolution studies, the best conditions were achieved using a United States Pharmacopeia Dissolution Apparatus 2 (paddle) at 50 rpm and with 900 mL 0.1 M hydrochloric acid as the dissolution medium, presenting satisfactory results during the validation tests. In addition, the kinetic parameters of drug release were investigated using model-dependent methods, and the dissolution profiles were best described by the first-order model. Therefore, the proposed methods were successfully applied for the assay and dissolution analysis of PB in commercial tablets.

Fatigue and quasi‐static mechanical behavior of bio‐degradable porous biomaterials based on magnesium alloys

PubMed Central

Ahmadi, S. M.; Lietaert, K.; Tümer, N.; Li, Y.; Amin Yavari, S.; Zadpoor, A. A.

2018-01-01

Abstract Magnesium and its alloys have the intrinsic capability of degrading over time in vivo without leaving toxic degradation products. They are therefore suitable for use as biodegradable scaffolds that are replaced by the regenerated tissues. One of the main concerns for such applications, particularly in load‐bearing areas, is the sufficient mechanical integrity of the scaffold before sufficient volumes of de novo tissue is generated. In the majority of the previous studies on the effects of biodegradation on the mechanical properties of porous biomaterials, the change in the elastic modulus has been studied. In this study, variations in the static and fatigue mechanical behavior of porous structures made of two different Mg alloys (AZ63 and M2) over different dissolution times ( 6, 12, and 24 h) have been investigated. The results showed an increase in the mechanical properties obtained from stress–strain curve (elastic modulus, yield stress, plateau stress, and energy absorption) after 6–12 h and a sharp decrease after 24 h. The initial increase in the mechanical properties may be attributed to the accumulation of corrosion products in the pores of the porous structure before degradation has considerably proceeded. The effects of mineral deposition was more pronounced for the elastic modulus as compared to other mechanical properties. That may be due to insufficient integration of the deposited particles in the structure of the magnesium alloys. While the bonding of the parts being combined in a composite‐like material is of great importance in determining its yield stress, the effects of bonding strength of both parts is much lower in determining the elastic modulus. The results of the current study also showed that the dissolution rates of the studied Mg alloys were too high for direct use in human body. © 2018 Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1798–1811, 2018. PMID:29468807

Balance Performance Is Task Specific in Older Adults.

PubMed

Dunsky, Ayelet; Zeev, Aviva; Netz, Yael

2017-01-01

Balance ability among the elderly is a key component in the activities of daily living and is divided into two types: static and dynamic. For clinicians who wish to assess the risk of falling among their elderly patients, it is unclear if more than one type of balance test can be used to measure their balance impairment. In this study, we examined the association between static balance measures and two dynamic balance field tests. One hundred and twelve community-dwelling older adults (mean age 74.6) participated in the study. They underwent the Tetrax static postural assessment and then performed the Timed Up and Go (TUG) and the Functional Reach (FR) Test as dynamic balance tests. In general, low-moderate correlations were found between the two types of balance tests. For women, age and static balance parameters explained 28.1-40.4% of the variance of TUG scores and 14.6-24% of the variance of FR scores. For men, age and static balance parameters explained 9.5-31.2% of the variance of TUG scores and 23.9-41.7% of the variance of FR scores. Based on our findings, it is suggested that a combination of both static and dynamic tests be used for assessing postural balance ability.

Comparison of spray drying, electroblowing and electrospinning for preparation of Eudragit E and itraconazole solid dispersions.

PubMed

Sóti, Péter Lajos; Bocz, Katalin; Pataki, Hajnalka; Eke, Zsuzsanna; Farkas, Attila; Verreck, Geert; Kiss, Éva; Fekete, Pál; Vigh, Tamás; Wagner, István; Nagy, Zsombor K; Marosi, György

2015-10-15

Three solvent based methods: spray drying (SD), electrospinning (ES) and air-assisted electrospinning (electroblowing; EB) were used to prepare solid dispersions of itraconazole and Eudragit E. Samples with the same API/polymer ratios were prepared in order to make the three technologies comparable. The structure and morphology of solid dispersions were identified by scanning electron microscopy and solid phase analytical methods such as, X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and Raman chemical mapping. Moreover, the residual organic solvents of the solid products were determined by static headspace-gas chromatography/mass spectroscopy measurements and the wettability of samples was characterized by contact angle measurement. The pharmaceutical performance of the three dispersion type, evaluated by dissolution tests, proved to be very similar. According to XRPD and DSC analyses, made after the production, all the solid dispersions were free of any API crystal clusters but about 10 wt% drug crystallinity was observed after three months of storage in the case of the SD samples in contrast to the samples produced by ES and EB in which the polymer matrix preserved the API in amorphous state. Copyright © 2015 Elsevier B.V. All rights reserved.

32. VIEW LOOKING EAST AT THE STATIC TEST TOWER WHILE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

32. VIEW LOOKING EAST AT THE STATIC TEST TOWER WHILE A JUPITER MISSILE IS BEING POSITIONED ONTO THE TEST TOWER. DATE AND PHOTOGRAPHER UNKNOWN, MSFC PHOTO LAB. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

[Static posturography versus clinical tests in elderly people with vestibular pathology].

PubMed

Ortuño-Cortés, Miguel A; Martín-Sanz, Eduardo; Barona-de Guzmán, Rafael

2008-01-01

Balance can be quantified by clinical tests and through instrumental studies. The objective of this paper is to determine the correlation between static posturography and 4 clinical tests of balance in elderly people with vestibular disorders and to identify its capability to discriminate the groups studied. 60 patients with vestibular disorders and 60 healthy subjects performed 4 clinical tests (one leg standing with opened eyes, Timed Up and Go, Tinetti and Berg tests) and a static posturography analysis (NedSVE/IBV system) under 4 conditions: Romberg Test, Eyes Open (REO), Romberg Test, Eyes Closed (REC), Romberg Test on Foam with Eyes Open (RFEO), and Romberg Test on Foam with Eyes Closed (RFEC). RFEO correlated best with the clinical tests and RFEC was the worst. RFEO distinguished between healthy individuals and decompensated patients. RFEO gave the best information about postural balance in the elderly. RFEC was not useful. Static posturography can be useful to distinguish vestibular compensation status.

Martian Atmospheric Pressure Static Charge Elimination Tool

NASA Technical Reports Server (NTRS)

Johansen, Michael R.

2014-01-01

A Martian pressure static charge elimination tool is currently in development in the Electrostatics and Surface Physics Laboratory (ESPL) at NASA's Kennedy Space Center. In standard Earth atmosphere conditions, static charge can be neutralized from an insulating surface using air ionizers. These air ionizers generate ions through corona breakdown. The Martian atmosphere is 7 Torr of mostly carbon dioxide, which makes it inherently difficult to use similar methods as those used for standard atmosphere static elimination tools. An initial prototype has been developed to show feasibility of static charge elimination at low pressure, using corona discharge. A needle point and thin wire loop are used as the corona generating electrodes. A photo of the test apparatus is shown below. Positive and negative high voltage pulses are sent to the needle point. This creates positive and negative ions that can be used for static charge neutralization. In a preliminary test, a floating metal plate was charged to approximately 600 volts under Martian atmospheric conditions. The static elimination tool was enabled and the voltage on the metal plate dropped rapidly to -100 volts. This test data is displayed below. Optimization is necessary to improve the electrostatic balance of the static elimination tool.

Influence of Dissolution Media and Presence of Alcohol on the In Vitro Performance of Pharmaceutical Products Containing an Insoluble Drug.

PubMed

Friuli, Valeria; Bruni, Giovanna; Musitelli, Giorgio; Conte, Ubaldo; Maggi, Lauretta

2018-01-01

The purpose of this investigation is to determine how the dissolution media may influence the release rate of an insoluble drug in in vitro conditions. Some oral dosage forms containing ibuprofen, a molecule that shows pH-dependent solubility, are tested. They are evaluated in different media to simulate the gastrointestinal transit at paddle rotation speeds of 50 and 100 rpm. Moreover, the potential effect of different ethanol concentrations on drug release is tested. The dissolution profiles of the tablets show a similar behavior in water (pH 1.0) and phosphate buffer (pH 4.5) where the 2 doses are not completely dissolved. The soft capsules show a different behavior: a certain amount of ibuprofen, which is in solution inside the capsule, reprecipitates in water and in the pH 4.5 buffer. Instead, ibuprofen dissolves rapidly in the pH 6.8 buffer from all the formulations. In the water-ethanol solutions, the dissolution curves show a valuable increase in the drug dissolved at higher ethanol concentrations. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

Template occluded SBA-15: An effective dissolution enhancer for poorly water-soluble drug

NASA Astrophysics Data System (ADS)

Tingming, Fu; Liwei, Guo; Kang, Le; Tianyao, Wang; Jin, Lu

2010-09-01

The aim of the present work was to improve the dissolution rate of piroxicam by inclusion into template occluded SBA-15. Our strategy involves directly introducing piroxicam into as-prepared SBA-15 occluded with P123 (EO 20PO 70EO 20) by self assembling method in acetonitrile/methylene chloride mixture solution. Ultraviolet spectrometry experiment and thermogravimetric analysis-differential scanning calorimetry (TG-DSC) profiles show that the piroxicam and P123 contents in the inclusion compound are 12 wt% and 28 wt%, respectively. X-ray powder diffraction and DSC analysis reveal that the included piroxicam is arranged in amorphous form. N 2 adsorption-desorption experiment indicates that the piroxicam has been introduced to the mesopores instead of precipitating at the outside of the silica material. The inclusion compound was submitted to in vitro dissolution tests, the results show that the piroxicam dissolve from template occluded inclusion compound more rapidly, than these from the piroxicam crystalline and template removed samples in all tested conditions. Thus a facile method to improve the dissolution rate of poorly water-soluble drug was established, and this discovery opens a new avenue for the utilization of templates used for the synthesis of mesoporous materials.

Determining the dissolution rates of actinide glasses: A time and temperature Product Consistency Test study

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

Daniel, W.E.; Best, D.R.

1995-12-01

Vitrification has been identified as one potential option for the e materials such as Americium (Am), Curium (Cm), Neptunium (Np), and Plutonium (Pu). A process is being developed at the Savannah River Site to safely vitrify all of the highly radioactive Am/Cm material and a portion of the fissile (Pu) actinide materials stored on site. Vitrification of the Am/Cm will allow the material to be transported and easily stored at the Oak Ridge National Laboratory. The Am/Cm glass has been specifically designed to be (1) highly durable in aqueous environments and (2) selectively attacked by nitric acid to allow recoverymore » of the valuable Am and Cm isotopes. A similar glass composition will allow for safe storage of surplus plutonium. This paper will address the composition, relative durability, and dissolution rate characteristics of the actinide glass, Loeffler Target, that will be used in the Americium/Curium Vitrification Project at Westinghouse Savannah River Company near Aiken, South Carolina. The first part discusses the tests performed on the Loeffler Target Glass concerning instantaneous dissolution rates. The second part presents information concerning pseudo-activation energy for the one week glass dissolution process.« less

14 CFR 23.785 - Seats, berths, litters, safety belts, and shoulder harnesses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... combination of structural analysis and static load tests to limit load; or (3) Static load tests to ultimate... OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY... resulting from the ultimate static load factors prescribed in § 23.561(b)(2) of this part. Each occupant...

14 CFR 23.785 - Seats, berths, litters, safety belts, and shoulder harnesses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... combination of structural analysis and static load tests to limit load; or (3) Static load tests to ultimate... OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY... resulting from the ultimate static load factors prescribed in § 23.561(b)(2) of this part. Each occupant...

14 CFR 23.785 - Seats, berths, litters, safety belts, and shoulder harnesses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... combination of structural analysis and static load tests to limit load; or (3) Static load tests to ultimate... OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY... resulting from the ultimate static load factors prescribed in § 23.561(b)(2) of this part. Each occupant...

14 CFR 23.785 - Seats, berths, litters, safety belts, and shoulder harnesses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... combination of structural analysis and static load tests to limit load; or (3) Static load tests to ultimate... OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY... resulting from the ultimate static load factors prescribed in § 23.561(b)(2) of this part. Each occupant...

14 CFR 23.785 - Seats, berths, litters, safety belts, and shoulder harnesses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... combination of structural analysis and static load tests to limit load; or (3) Static load tests to ultimate... OF TRANSPORTATION AIRCRAFT AIRWORTHINESS STANDARDS: NORMAL, UTILITY, ACROBATIC, AND COMMUTER CATEGORY... resulting from the ultimate static load factors prescribed in § 23.561(b)(2) of this part. Each occupant...

14 CFR Appendix E to Part 43 - Altimeter System Test and Inspection

Code of Federal Regulations, 2011 CFR

2011-01-01

... made that would affect the relationship between air pressure in the static pressure system and true ambient static air pressure for any flight condition. (b) Altimeter: (1) Test by an appropriately rated... inspections required by § 91.411 shall comply with the following: (a) Static pressure system: (1) Ensure...

The Effect of Simulated Microgravity Environment of RWV Bioreactors on Surface Reactions and Adsorption of Serum Proteins on Bone-bioactive Microcarriers

NASA Technical Reports Server (NTRS)

Radin, Shula; Ducheyne, P.; Ayyaswamy, P. S.

2003-01-01

Biomimetically modified bioactive materials with bone-like surface properties are attractive candidates for use as microcarriers for 3-D bone-like tissue engineering under simulated microgravity conditions of NASA designed rotating wall vessel (RWV) bioreactors. The simulated microgravity environment is attainable under suitable parametric conditions of the RWV bioreactors. Ca-P containing bioactive glass (BG), whose stimulatory effect on bone cell function had been previously demonstrated, was used in the present study. BG surface modification via reactions in solution, resulting formation of bone-like minerals at the surface and adsorption of serum proteins is critical for obtaining the stimulatory effect. In this paper, we report on the major effects of simulated microgravity conditions of the RWV on the BG reactions surface reactions and protein adsorption in physiological solutions. Control tests at normal gravity were conducted at static and dynamic conditions. The study revealed that simulated microgravity remarkably enhanced reactions involved in the BG surface modification, including BG dissolution, formation of bone-like minerals at the surface and adsorption of serum proteins. Simultaneously, numerical models were developed to simulate the mass transport of chemical species to and from the BG surface under normal gravity and simulated microgravity conditions. The numerical results showed an excellent agreement with the experimental data at both testing conditions.

Comparison of Quality and Output of Different Optimal Perimetric Testing Approaches in Children With Glaucoma.

PubMed

Patel, Dipesh E; Cumberland, Phillippa M; Walters, Bronwen C; Russell-Eggitt, Isabelle; Brookes, John; Papadopoulos, Maria; Khaw, Peng Tee; Viswanathan, Ananth C; Garway-Heath, David; Cortina-Borja, Mario; Rahi, Jugnoo S

2018-02-01

There is limited evidence to support the development of guidance for visual field testing in children with glaucoma. To compare different static and combined static/kinetic perimetry approaches in children with glaucoma. Cross-sectional, observational study recruiting children prospectively between May 2013 and June 2015 at 2 tertiary specialist pediatric ophthalmology centers in London, England (Moorfields Eye Hospital and Great Ormond Street Hospital). The study included 65 children aged 5 to 15 years with glaucoma (108 affected eyes). A comparison of test quality and outcomes for static and combined static/kinetic techniques, with respect to ability to quantify glaucomatous loss. Children performed perimetric assessments using Humphrey static (Swedish Interactive Thresholding Algorithm 24-2 FAST) and Octopus combined static tendency-oriented perimetry/kinetic perimetry (isopter V4e, III4e, or I4e) in a single sitting, using standardized clinical protocols, administered by a single examiner. Information was collected about test duration, completion, and quality (using automated reliability indices and our qualitative Examiner-Based Assessment of Reliability score). Perimetry outputs were scored using the Aulhorn and Karmeyer classification. One affected eye in 19 participants was retested with Swedish Interactive Thresholding Algorithm 24-2 FAST and 24-2 standard algorithms. Sixty-five children (33 girls [50.8%]), with a median age of 12 years (interquartile range, 9-14 years), were tested. Test quality (Examiner-Based Assessment of Reliability score) improved with increasing age for both Humphrey and Octopus strategies and were equivalent in children older than 10 years (McNemar test, χ2 = 0.33; P = .56), but better-quality tests with Humphrey perimetry were achieved in younger children (McNemar test, χ2 = 4.0; P = .05). Octopus and Humphrey static MD values worse than or equal to -6 dB showed disagreement (Bland-Altman, mean difference, -0.70; limit of agreement, -7.74 to 6.35) but were comparable when greater than this threshold (mean difference, -0.03; limit of agreement, -2.33 to 2.27). Visual field classification scores for static perimetry tests showed substantial agreement (linearly weighted κ, 0.79; 95% CI, 0.65-0.93), although 25 of 80 (31%) were graded with a more severe defect for Octopus static perimetry. Of the 7 severe cases of visual field loss (grade 5), 5 had lower kinetic than static classification scores. A simple static perimetry approach potentially yields high-quality results in children younger than 10 years. For children older than 10 years, without penalizing quality, the addition of kinetic perimetry enabled measurement of far-peripheral sensitivity, which is particularly useful in children with severe visual field restriction.

Effect on fan flow characteristics of length and axial location of a cascade thrust reverser

NASA Technical Reports Server (NTRS)

Dietrich, D. A.

1975-01-01

A series of static tests were conducted on a model fan with a diameter of 14.0 cm to determine the fan operating characteristics, the inlet static pressure contours, the fan-exit total and static pressure contours, and the fan-exit pressure distortion parameters associated with the installation of a partial-circumferential-emission cascade thrust reverser. The tests variables included the cascade axial length, the axial location of the reverser, and the type of fan inlet. It was shown that significant total and static pressure distortions were produced in the fan aft duct, and that some configurations induced a static pressure distortion at the fan face. The amount of flow passed by the fan and the level of the flow distortions were dependent upon all the variables tested.

29. SATURN ROCKET ENGINE LOCATED ON NORTH SIDE OF STATIC ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

29. SATURN ROCKET ENGINE LOCATED ON NORTH SIDE OF STATIC TEST STAND - DETAILS OF THE EXPANSION NOZZLE. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

GENERAL VIEW LOOKING SOUTH AT THE SATURN I STATIC TEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

GENERAL VIEW LOOKING SOUTH AT THE SATURN I STATIC TEST STAND. NOTE THE FIRST STAGE OF THE SATURN I ROCKET ON DISPLAY TO THE LEFT OF THE TEST STAND. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

In Vitro-In Vivo Predictive Dissolution-Permeation-Absorption Dynamics of Highly Permeable Drug Extended-Release Tablets via Drug Dissolution/Absorption Simulating System and pH Alteration.

PubMed

Li, Zi-Qiang; Tian, Shuang; Gu, Hui; Wu, Zeng-Guang; Nyagblordzro, Makafui; Feng, Guo; He, Xin

2018-05-01

Each of dissolution and permeation may be a rate-limiting factor in the absorption of oral drug delivery. But the current dissolution test rarely took into consideration of the permeation property. Drug dissolution/absorption simulating system (DDASS) valuably gave an insight into the combination of drug dissolution and permeation processes happening in human gastrointestinal tract. The simulated gastric/intestinal fluid of DDASS was improved in this study to realize the influence of dynamic pH change on the complete oral dosage form. To assess the effectiveness of DDASS, six high-permeability drugs were chosen as model drugs, including theophylline (pK a1  = 3.50, pK a2  = 8.60), diclofenac (pK a  = 4.15), isosorbide 5-mononitrate (pK a  = 7.00), sinomenine (pK a  = 7.98), alfuzosin (pK a  = 8.13), and metoprolol (pK a  = 9.70). A general elution and permeation relationship of their commercially available extended-release tablets was assessed as well as the relationship between the cumulative permeation and the apparent permeability. The correlations between DDASS elution and USP apparatus 2 (USP2) dissolution and also between DDASS permeation and beagle dog absorption were developed to estimate the predictability of DDASS. As a result, the common elution-dissolution relationship was established regardless of some variance in the characteristic behavior between DDASS and USP2 for drugs dependent on the pH for dissolution. Level A in vitro-in vivo correlation between DDASS permeation and dog absorption was developed for drugs with different pKa. The improved DDASS will be a promising tool to provide a screening method on the predictive dissolution-permeation-absorption dynamics of solid drug dosage forms in the early-phase formulation development.

Dissolution Kinetics of Meta-Torbernite under Circum-neutral to Alkaline Conditions

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

Wellman, Dawn M.; McNamara, Bruce K.; Bacon, Diana H.

2009-12-21

Autunite group minerals have been identified in contaminated sediments as the long-term controlling phase of uranium. Meta-torbernite, has been identified in subsurface environments which were subjected to co-contaminant disposal practices from past nuclear weapons and fuel operations. Under these conditions the mobility of uranium in subsurface pore waters is limited by the rate of meta-torbernite dissolution; however, there are no known investigations which report the dissolution behavior of meta-torbernite. The purpose of this investigation was to conduct a series of single-pass flow-through (SPFT) tests to 1) quantify the effect of temperature (23 - 90oC) and pH (6 -10) on meta-torbernitemore » dissolution, 2) compare the dissolution of meta-torbernite to other autunite-group minerals, and 3) evaluate the effect of aqueous phosphate on the dissolution kinetics of meta-torbernite. Results presented here illustrate meta-torbernite dissolution rates increase by ~100X over the pH interval of 6 to 10 (eta = 0.59 ± 0.07), irrespective of temperature. The power law coefficient for meta-torbernite, eta = 0.59 ± 0.07, is greater than that quantified for Ca-meta-autunite, eta = 0.42 ± 0.12. This suggests the stability of meta-torbernite is greater than that of meta-autunite, which is reflected in the predicted stability constants. The rate equation for the dissolution of meta-torbernite as a function of aqueous phosphate concentration is log rdissol (mol m-2 sec-1) = -4.7 x 10-13 + 4.1 x 10-10 [PO43-].« less

In Vivo Predictive Dissolution: Comparing the Effect of Bicarbonate and Phosphate Buffer on the Dissolution of Weak Acids and Weak Bases.

PubMed

Krieg, Brian J; Taghavi, Seyed Mohammad; Amidon, Gordon L; Amidon, Gregory E

2015-09-01

Bicarbonate is the main buffer in the small intestine and it is well known that buffer properties such as pKa can affect the dissolution rate of ionizable drugs. However, bicarbonate buffer is complicated to work with experimentally. Finding a suitable substitute for bicarbonate buffer may provide a way to perform more physiologically relevant dissolution tests. The dissolution of weak acid and weak base drugs was conducted in bicarbonate and phosphate buffer using rotating disk dissolution methodology. Experimental results were compared with the predicted results using the film model approach of (Mooney K, Mintun M, Himmelstein K, Stella V. 1981. J Pharm Sci 70(1):22-32) based on equilibrium assumptions as well as a model accounting for the slow hydration reaction, CO2 + H2 O → H2 CO3 . Assuming carbonic acid is irreversible in the dehydration direction: CO2 + H2 O ← H2 CO3 , the transport analysis can accurately predict rotating disk dissolution of weak acid and weak base drugs in bicarbonate buffer. The predictions show that matching the dissolution of weak acid and weak base drugs in phosphate and bicarbonate buffer is possible. The phosphate buffer concentration necessary to match physiologically relevant bicarbonate buffer [e.g., 10.5 mM (HCO3 (-) ), pH = 6.5] is typically in the range of 1-25 mM and is very dependent upon drug solubility and pKa . © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Static and dynamic pile testing of reinforced concrete piles with structure integrated fibre optic strain sensors

NASA Astrophysics Data System (ADS)

Schilder, Constanze; Kohlhoff, Harald; Hofmann, Detlef; Basedau, Frank; Habel, Wolfgang R.; Baeßler, Matthias; Niederleithinger, Ernst; Georgi, Steven; Herten, Markus

2013-05-01

Static and dynamic pile tests are carried out to determine the load bearing capacity and the quality of reinforced concrete piles. As part of a round robin test to evaluate dynamic load tests, structure integrated fibre optic strain sensors were used to receive more detailed information about the strains along the pile length compared to conventional measurements at the pile head. This paper shows the instrumentation of the pile with extrinsic Fabry-Perot interferometers sensors and fibre Bragg gratings sensors together with the results of the conducted static load test as well as the dynamic load tests and pile integrity tests.

Mitigating Upsets in SRAM Based FPGAs from the Xilinix Virtex 2 Family

NASA Technical Reports Server (NTRS)

Swift, Gary M.; Yui, Candice C.; Carmichael, Carl; Koga, Rocky; George, Jeffrey S.

2003-01-01

This slide presentation reviews the single event upset static testing of the Virtex II field programmable gate arrays (FPGA) that were tested in protons and heavy-ions. The test designs and static and dynamic test results are reviewed.

Pilot Study: Foam Wedge Chin Support Static Tolerance Testing

DTIC Science & Technology

2017-10-24

AFRL-SA-WP-SR-2017-0026 Pilot Study : Foam Wedge Chin Support Static Tolerance Testing Austin M. Fischer, BS1; William W...COVERED (From – To) April – October 2017 4. TITLE AND SUBTITLE Pilot Study : Foam Wedge Chin Support Static Tolerance Testing 5a. CONTRACT NUMBER...prototype to mitigate the increase in helmet weight and forward center of gravity. The purpose of this pilot study was to determine the feasibility and

Dynamic Breaking Tests of Airplane Parts

NASA Technical Reports Server (NTRS)

Hertel, Heinrich

1933-01-01

The static stresses of airplane parts, the magnitude of which can be determined with the aid of static load assumptions, are mostly superposed by dynamic stresses, the magnitude of which has been but little explored. The object of the present investigation is to show how the strength of airplane parts can best be tested with respect to dynamic stresses with and without superposed static loading, and to what extent the dynamic strength of the parts depends on their structural design. Experimental apparatus and evaluation methods were developed and tried for the execution of vibration-strength tests with entire structural parts both with and without superposed static loading. Altogether ten metal spars and spar pieces and two wooden spars were subjected to vibration breaking tests.

Subsonic static and dynamic stability characteristics of the test technique demonstrator NASP configuration

NASA Technical Reports Server (NTRS)

Boyden, Richmond P.; Dress, David A.; Fox, Charles H., Jr.; Huffman, Jarrett K.; Cruz, Christopher I.

1993-01-01

The paper describes the procedure used for and the results obtained of wind-tunnel tests of the National Aerospace Plane (NASP) configuration, which were conducted in the NASA Langley Research Center High Speed Tunnel using a blended body NASP configuration designed by the research center. Static and dynamic stability characteristics were measured at Mach numbers 0.3, 0.6, and 0.8. In addition to tests of the baseline configuration, component buildup tests with a canard surface and with a body flap were carried out. Results demonstrated a positive static stability of the baseline configuration, except at the higher angles of attack at Mach 0.8. A good agreement was found between the inphase dynamic parameters and the corresponding static data.

Kinetics of dissolution of thorium and uranium doped britholite ceramics

NASA Astrophysics Data System (ADS)

Dacheux, N.; Du Fou de Kerdaniel, E.; Clavier, N.; Podor, R.; Aupiais, J.; Szenknect, S.

2010-09-01

In the field of immobilization of actinides in phosphate-based ceramics, several thorium and uranium doped britholite samples were submitted to leaching tests. The normalized dissolution rates determined for several pH values, temperatures and acidic media from the calcium release range from 4.7 × 10 -2 g m -2 d -1 to 21.6 g m -2 d -1. Their comparison with that determined for phosphorus, thorium and uranium revealed that the dissolution is clearly incongruent for all the conditions examined. Whatever the leaching solution considered, calcium and phosphorus elements were always released with higher RL values than the other elements (Nd, Th, U). Simultaneously, thorium was found to quickly precipitate as alteration product, leading to diffusion phenomena for uranium. For all the media considered, the uranium release is higher than that of thorium, probably due to its oxidation from tetravalent oxidation state to uranyl. Moreover, the evaluation of the partial order related to proton concentration and the apparent energy of activation suggest that the reaction of dissolution is probably controlled by surface chemical reactions occurring at the solid/liquid interface. Finally, comparative leaching tests performed in sulphuric acid solutions revealed a significant influence of such media on the chemical durability of the leached pellets, leading to higher normalized dissolution rates for all the elements considered. On the basis of the results of chemical speciation, this difference was mainly explained in the light of higher complexion constants by sulfate ions compared to nitrate, chloride and phosphate.

Structural properties and adsorption capacity of holocellulose aerogels synthesized from an alkali hydroxide-urea solution

NASA Astrophysics Data System (ADS)

Kwon, Gu-Joong; Kim, Dae-Young; Hwang, Jae-Hyun; Kang, Joo-Hyon

2014-05-01

A tulip tree was used to synthesize a holocellulose aerogel from an aqueous alkali hydroxide-urea solution with the substitution of an organic solvent followed by freeze-drying. For comparison, the synthesized holocellulose aerogels were divided into two groups according to the source of the hydrogel, an upper suspended layer and a bottom concentrated layer of the centrifuged solution of cellulose and NaOH/urea solvents. We investigated the effects of the temperature of the pre-cooled NaOH/urea solution ( i.e., dissolution temperature) on the pore structure and the adsorption capacity of the holocellulose aerogel. A nano-fibrillar network structure of the holocellulose aerogel was observed, with little morphological difference in pore structure for different dissolution temperatures. Both micropores and mesopores were observed in the holocellulose aerogel. The specific surface area of the holocellulose aerogel was generally greater at lower dissolution temperatures. In a series of adsorption tests using methylene blue, the holocellulose aerogel showed the greatest adsorption capacity at the lowest dissolution temperature tested (-2°C). However, the dissolution temperature generally had little effect on the adsorption capacity. The holocellulose aerogel produced from the upper suspended layer of the centrifuged hydrogel solution showed a greater porosity and adsorption capacity than the one produced from the bottom concentrated layer. Overall, the aerogel made by utilizing a delignified tulip tree display a high surface area and a high adsorption property, indicating its possible application in eco-friendly adsorption materials.

Evaluation of palatability of 10 commercial amlodipine orally disintegrating tablets by gustatory sensation testing, OD-mate as a new disintegration apparatus and the artificial taste sensor.

PubMed

Uchida, Takahiro; Yoshida, Miyako; Hazekawa, Mai; Haraguchi, Tamami; Furuno, Hiroyuki; Teraoka, Makoto; Ikezaki, Hidekazu

2013-09-01

The purpose of this study was to evaluate and compare the palatability of 10 formulations (the original manufacturer's formulation and nine generics) of amlodipine orally disintegrating tablets (ODTs) by means of human gustatory sensation testing, disintegration/dissolution testing and the evaluation of bitterness intensity using a taste sensor. Initially, the palatability, dissolution and bitterness intensity of the ODTs were evaluated in gustatory sensation tests. Second, the disintegration times of the ODTs were measured using the OD-mate, a newly developed apparatus for measuring the disintegration of ODTs, and lastly, the bitterness intensities were evaluated using an artificial taste sensor. Using factor analysis, the factors most affecting the palatability of amlodipine ODTs were found to be disintegration and taste. There was high correlation between the disintegration times of the 10 amlodipine ODTs estimated in human gustatory testing and those found using the OD-mate. The bitterness intensities of amlodipine ODTs 10, 20 and 30 s after starting the conventional brief dissolution test and the values determined by the taste sensor were highly correlated with the bitterness intensities determined in gustatory sensation testing. The OD-mate and the taste sensor may be useful for predicting the disintegration and bitterness intensity of amlodipine ODTs in the mouth. © 2013 Royal Pharmaceutical Society.

Crystal forms of the hydrogen oxalate salt of o-desmethylvenlafaxine.

PubMed

Dichiarante, Elena; Curzi, Marco; Giaffreda, Stefano L; Grepioni, Fabrizia; Maini, Lucia; Braga, Dario

2015-06-01

To prepare new crystalline forms of the antidepressant o-desmethylvenlafaxine salt as potential new commercial forms and evaluate their physicochemical properties, in particular the dissolution rate. A new hydrogen oxalate salt of o-desmethylvenlafaxine hydrogen oxalate (ODV-OX) was synthesized, and a polymorph screening was performed using different solvents and crystallization conditions. Crystalline forms were characterized by a combination of solid-state techniques: X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, FT-IR spectroscopy and single crystal X-ray diffraction. The stability of all crystalline phases was tested under International Conference on Harmonisation (ICH) conditions (40°C and 75% Relative Humidity (RH)) for 1 week. Dissolution tests were performed on the hydrogen oxalate salt ODV-OX Form 1 and compared with dissolution test on the commercial form of the succinate salt of o-desmethylvenlafaxine. Five crystalline forms of ODV-OX were isolated, namely three hydrated forms (Form 1, Form 2, Form 3) and two anhydrous forms (Form 4 and Form 5). Comparative solubility tests on ODV-OX Form 1 and o-desmethylvenlafaxine succinate evidenced a significant increase in solubility for the hydrogen oxalate salt (142 g/l) with respect to the succinate salt (70 g/l). © 2015 Royal Pharmaceutical Society.

A comparative study of first-derivative spectrophotometry and column high-performance liquid chromatography applied to the determination of repaglinide in tablets and for dissolution testing.

PubMed

AlKhalidi, Bashar A; Shtaiwi, Majed; AlKhatib, Hatim S; Mohammad, Mohammad; Bustanji, Yasser

2008-01-01

A fast and reliable method for the determination of repaglinide is highly desirable to support formulation screening and quality control. A first-derivative UV spectroscopic method was developed for the determination of repaglinide in tablet dosage form and for dissolution testing. First-derivative UV absorbance was measured at 253 nm. The developed method was validated for linearity, accuracy, precision, limit of detection (LOD), and limit of quantitation (LOQ) in comparison to the U.S. Pharmacopeia (USP) column high-performance liquid chromatographic (HPLC) method. The first-derivative UV spectrophotometric method showed excellent linearity [correlation coefficient (r) = 0.9999] in the concentration range of 1-35 microg/mL and precision (relative standard deviation < 1.5%). The LOD and LOQ were 0.23 and 0.72 microg/mL, respectively, and good recoveries were achieved (98-101.8%). Statistical comparison of results of the first-derivative UV spectrophotometric and the USP HPLC methods using the t-test showed that there was no significant difference between the 2 methods. Additionally, the method was successfully used for the dissolution test of repaglinide and was found to be reliable, simple, fast, and inexpensive.

Strategy for Alternative Occupant Volume Testing

DOT National Transportation Integrated Search

2009-10-20

This paper describes plans for a series of quasi-static : compression tests of rail passenger equipment. These tests are : designed to evaluate the strength of the occupant volume under : static loading conditions. The research plan includes a detail...

The Controversial Role of Inter-diffusion in Glass Alteration

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

Gin, Stephane; Neill, Lindsay; Fournier, M.

2016-11-15

Current kinetic models for nuclear waste glasses (e.g. GM2001, GRAAL) are based on a set of mechanisms that have been generally agreed upon within the international waste glass community. These mechanisms are: hydration of the glass, ion exchange reactions (the two processes are referred as inter-diffusion), hydrolysis of the silicate network, and condensation/precipitation of partly or completely hydrolyzed species that produces a porous and amorphous layer and crystalline phases on surface of the altered glass. Recently, a new idea with origins in the mineral dissolution community has been proposed that excludes inter-diffusion process as a potential rate-limiting mechanism. To understandmore » how the so-called interfacial dissolution/precipitation model can change the current understanding of glass behavior, a key experiment used to account for this model was replicated to further revisit the interpretation. This experiment was performed at 50°C, with SON68 glass, in static mode, deionized water and S/V ratio of 10 m-1 for 6 months. It turn out that glass alters in an intermediate kinetic regime between the forward and the residual rate. According to previous and new solid characterizations, it is concluded that neither a simple inter-diffusion model nor the interfacial dissolution precipitation model can account for the observed elemental profiles within the alteration layer. More generally, far and close-to-saturation conditions must be distinguished and literature provides evidences that inter-diffusion takes place in slightly acidic conditions and far from saturation. However, closer to saturation, when a sufficiently dense layer is formed, a new approach is proposed requiring a full description of chemical reactions taking place within the alteration layer and involving water molecules as it is thought that water accessibility to the pristine glass is the rate-limiting process.« less

Influence of variable rates of neritic carbonate deposition on atmospheric carbon dioxide and pelagic sediments

NASA Technical Reports Server (NTRS)

Walker, J. C.; Opdyke, B. C.

1995-01-01

Short-term imbalances in the global cycle of shallow water calcium carbonate deposition and dissolution may be responsible for much of the observed Pleistocene change in atmospheric carbon dioxide content. However, any proposed changes in the alkalinity balance of the ocean must be reconciled with the sedimentary record of deep-sea carbonates. The possible magnitude of the effect of shallow water carbonate deposition on the dissolution of pelagic carbonate can be tested using numerical simulations of the global carbon cycle. Boundary conditions can be defined by using extant shallow water carbonate accumulation data and pelagic carbonate deposition/dissolution data. On timescales of thousands of years carbonate deposition versus dissolution is rarely out of equilibrium by more than 1.5 x 10(13) mole yr-1. Results indicate that the carbonate chemistry of the ocean is rarely at equilibrium on timescales less than 10 ka. This disequilibrium is probably due to sea level-induced changes in shallow water calcium carbonate deposition/dissolution, an interpretation that does not conflict with pelagic sedimentary data from the central Pacific.

[Study on solid dispersion of copovidone-based tanshinone II(A)].

PubMed

Jiang, Yan-Rong; Zhang, Zhen-Hai; Xia, Hai-Jiang; Jia, Xiao-Bin

2013-01-01

To apply PVP-S630 in the preparation of tanshinone II(A) (TS II(A)) solid dispersion, in order to improve its dissolution in vitro and reduce the moisture absorption of the solid dispersion. Tanshinone II(A) solid dispersion was prepared by spray drying method. Such analytical methods as SEM, DSC, XRD were used to characterize their phases and detect their dissolution, moisture absorption and stability. In the solid dispersion prepared with tanshinone II(A) and copovidone with proportion of 1:10, tanshinone II(A) was scattered on the surface of the carrier in the amorphous form, with a dissolution in vitro up to 100% at 0.5 h and a lower moisture absorption than PVP-K30 solid dispersion prepared with the same proportion. After a three-month accelerated stability test, it showed no significant change in drug dissolution and content. The solid dispersion prepared with copovidone as the carrier can significantly improve the dissolution of tanshinone II(A), with a relatively low moisture absorption and high stability, thereby having a good prospect of application.

Dynamic and Quasi-Static Grade Crossing Collision Tests

DOT National Transportation Integrated Search

2009-03-02

To support the development of a proposed rule [1], a fullscale : dynamic test and two full-scale quasi-static tests have : been performed on the posts of a state-of-the-art (SOA) end : frame. These tests were designed to evaluate the dynamic and : qu...

Static tensile and tensile creep testing of five ceramic fibers at elevated temperatures

NASA Technical Reports Server (NTRS)

Zimmerman, Richard S.; Adams, Donald F.

1989-01-01

Static tensile and tensile creep testing of five ceramic fibers at elevated temperature was performed. J.P. Stevens, Co., Astroquartz 9288 glass fiber; Nippon Carbon, Ltd., (Dow Corning) nicalon NLM-102 silicon carbide fiber; and 3M Company Nextel 312, 380, and 480 alumina/silica/boria fibers were supplied in unsized tows. Single fibers were separated from the tows and tested in static tension and tensile creep. Elevated test temperatures ranged from 400 C to 1300 C and varied for each fiber. Room temperature static tension was also performed. Computer software was written to reduce all single fiber test data into engineering constants using ASTM Standard Test Method D3379-75 as a reference. A high temperature furnace was designed and built to perform the single fiber elevated temperature testing up to 1300 C. A computerized single fiber creep apparatus was designed and constructed to perform four fiber creep tests simultaneously at temperatures up to 1300 C. Computer software was written to acquire and reduce all creep data.

Static tensile and tensile creep testing of five ceramic fibers at elevated temperatures

NASA Technical Reports Server (NTRS)

Zimmerman, Richard S.; Adams, Donald F.

1988-01-01

Static tensile and tensile creep testing of five ceramic fibers at elevated temperature was performed. J.P. Stevens, Co., Astroquartz 9288 glass fiber, Nippon Carbon, Ltd., (Dow Corning) Nicalon NLM-102 silicon carbide fiber, and 3M Company Nextel 312, 380, and 480 alumina/silica/boria fibers were supplied in unsized tows. Single fibers were separated from the tows and tested in static tension and tensile creep. Elevated test temperatures ranged from 400 to 1300 C and varied for each fiber. Room temperature static tension was also performed. Computer software was written to reduce all single fiber test data into engineering constants using ASTM Standard Test Method D3379-75 as a reference. A high temperature furnace was designed and built to perform the single fiber elevated temperature testing up to 1300 C. A computerized single fiber creep apparatus was designed and constructed to perform four fiber creep tests simultaneously at temperatures up to 1300 C. Computer software was written to acquire and reduce all creep data.

35. VIEW LOOKING NORTHWEST AT THE STATIC TEST TOWER. A ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

35. VIEW LOOKING NORTHWEST AT THE STATIC TEST TOWER. A 'DUMMY' SATURN I BOOSTER IS BEING HOISTED INTO THE TEST STAND TO TEST THE MATING OF THE BOOSTER AND THE TEST STAND. EARLY 1960, PHOTOGRAPHER UNKNOWN, MSFC PHOTO LAB. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

Asymmetric flow field-flow fractionation (AF4) for the quantification of nanoparticle release from tablets during dissolution testing.

PubMed

Engel, A; Plöger, M; Mulac, D; Langer, K

2014-01-30

Nanoparticles composed of poly(DL-lactide-co-glycolide) (PLGA) represent promising colloidal drug carriers for improved drug targeting. Although most research activities are focused on intravenous application of these carriers the peroral administration is described to improve bioavailability of poorly soluble drugs. Based on these insights the manuscript describes a model tablet formulation for PLGA-nanoparticles and especially its analytical characterisation with regard to a nanosized drug carrier. Besides physico-chemical tablet characterisation according to pharmacopoeias the main goal of the study was the development of a suitable analytical method for the quantification of nanoparticle release from tablets. An analytical flow field-flow fractionation (AF4) method was established and validated which enables determination of nanoparticle content in solid dosage forms as well as quantification of particle release during dissolution testing. For particle detection a multi-angle light scattering (MALS) detector was coupled to the AF4-system. After dissolution testing, the presence of unaltered PLGA-nanoparticles was successfully proved by dynamic light scattering and scanning electron microscopy. Copyright © 2013 Elsevier B.V. All rights reserved.

Bench Scale Saltcake Dissolution Test Report

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

BECHTOLD, D.B.; PACQUET, E.A.

A potential scenario for retrieving saltcake from single shell tanks is the ''Rainbird{reg_sign} sprinkler'' method. Water is distributed evenly across the surface of the saltcake and allowed to percolate by gravity through the waste. The salt dissolves in the water, forming a saturated solution. The saturated liquid is removed by a saltwell pump situated near the bottom of the tank. By this method, there is never a large inventory of liquid in the tank that could pose a threat of leakage. There are many variables or factors that can influence the hydrodynamics of this retrieval process. They include saltcake porosity;more » saltwell pumping rate; salt dissolution chemistry; factors that could promote flow channeling (e.g. tank walls, dry wells, inclusions or discontinuities in the saltcake); method of water distribution; plug formation due to crystal formations or accumulation of insoluble solids. A brief literature search indicates that very little experimental data exist on these aspects of saltcake dissolution (Wiersma 1996, 1997). The tests reported here were planned (Herting, 2000) to provide preliminary data and information for planning future, scaled-up tests of the sprinkler method.« less

In vitro stability, potency, and dissolution of duloxetine enteric-coated pellets after exposure to applesauce, apple juice, and chocolate pudding.

PubMed

Wells, Kevin A; Losin, William G

2008-07-01

Difficulty swallowing is a common problem in the clinical setting, particularly in elderly patients, and can significantly affect an individual's ability to maintain a proper level of nutrition. The purpose of this in vitro study was to determine if mixing duloxetine enteric-coated pellets in food substances is an acceptable alternative method for administering this oral formulation to patients with swallowing difficulties. To determine whether administration in food substances with varying pH values (applesauce and apple juice, pH = approximately 3.5; chocolate pudding, pH = approximately 5.5-6.0) affects the enteric coating of the formulation, duloxetine pellets (ie, the contents of a 20-mg duloxetine capsule) were exposed to applesauce, apple juice, and chocolate pudding at room temperature and tested in triplicate for potency and impurities; for dissolution, 6 replicates were tested. To assess product stability and integrity of the enteric coating, potency, impurities, and dissolution tests of the pellets were conducted and compared with pellets not exposed to food. The duloxetine pellets were extracted from the food material using a solution of 0.1 normal (N) hydrochloric acid (HCl) prepared from concentrated HCl (commercially available) and deionized water. For the potency and impurities tests, a 40:60 solution of acetonitrile and pH 8.0 phosphate buffer was used as the sample solvent to extract the active pharmaceutical ingredient from the formulation to prepare the samples for testing. The amount of active pharmaceutical ingredient released (in vitro dissolution) from the pellets after exposure to the food substances was determined using 2 media solutions, 0.1 N HCl followed by pH 6.8 phosphate buffer. Applesauce and chocolate pudding were selected as vehicles for oral administration, while apple juice was intended to be used as a wash for a nasogastric tube. Mean (SD) potency results for the 20-mg capsule strength were 20.256 (0.066), 20.222 (0.163), and 19.961 (0.668) mg/capsule for the comparator not exposed to food, the sample exposed to applesauce, and the sample exposed to apple juice, respectively. However, exposure to chocolate pudding altered the integrity of the pellet's enteric coating (mean [SD] potency results, 17.780 [1.605] mg/capsule). Results of impurities testing suggested that none of the test foods caused significant degradation of the drug product. Mean dissolution results found that after 2 hours in 0.1 N HCl, < or = 1% of duloxetine was released from the comparator and pellets exposed to applesauce and apple juice. However, the mean dissolution profile of the sample exposed to pudding reported near-total release (90%) after 2 hours in 0.1 N HCl during the gastric challenge portion of the dissolution test. Results from this study found that the enteric coating of duloxetine pellets mixed with applesauce or apple juice was not negatively affected. The pellets were stable at room temperature for < or = 2 hours and should quantitatively allow delivery of the full capsule dose, provided that the pellet integrity is maintained (ie, not crushed, chewed, or otherwise broken). Therefore, mixing duloxetine pellets with applesauce or apple juice appears to be an acceptable vehicle for administration. However, exposing the pellets to chocolate pudding damaged the pellets' enteric coating, suggesting that pudding may be an unacceptable vehicle for administration.

Uniform Corrosion and General Dissolution of Aluminum Alloys 2024-T3, 6061-T6, and 7075-T6

NASA Astrophysics Data System (ADS)

Huang, I.-Wen

Uniform corrosion and general dissolution of aluminum alloys was not as well-studied in the past, although it was known for causing significant amount of weight loss. This work comprises four chapters to understand uniform corrosion of aluminum alloys 2024-T3, 6061-T6, and 7075-T6. A preliminary weight loss experiment was performed for distinguishing corrosion induced weight loss attributed to uniform corrosion and pitting corrosion. The result suggested that uniform corrosion generated a greater mass loss than pitting corrosion. First, to understand uniform corrosion mechanism and kinetics in different environments, a series of static immersion tests in NaCl solutions were performed to provide quantitative measurement of uniform corrosion. Thereafter, uniform corrosion development as a function of temperature, pH, Cl-, and time was investigated to understand the influence of environmental factors. Faster uniform corrosion rate has been found at lower temperature (20 and 40°C) than at higher temperature (60 and 80°C) due to accelerated corrosion product formation at high temperatures inhibiting corrosion reactions. Electrochemical tests including along with scanning electron microscopy (SEM) were utilized to study the temperature effect. Second, in order to further understand the uniform corrosion influence on pit growth kinetics, a long term exposures for 180 days in both immersion and ASTM-B117 test were performed. Uniform corrosion induced surface recession was found to have limited impact on pit geometry regardless of exposure methods. It was also found that the competition for limited cathodic current from uniform corrosion the primary rate limiting factor for pit growth. Very large pits were found after uniform corrosion growth reached a plateau due to corrosion product coverage. Also, optical microscopy and focused ion beam (FIB) imaging has provided more insights of distinctive pitting geometry and subsurface damages found from immersion samples and B117 samples. Although uniform corrosion was studied in various electrolytes, the pH impact was still difficult to discern due to ongoing cathodic reactions that changed electrolyte pH with time. Therefore, buffered pH electrolytes with pH values of 3, 5, 8, and 10 were prepared static immersion tests. Electrochemical experiments were performed in each buffered pH conditions for understanding corrosion mechanisms. Uniform corrosion was found exhibiting higher corrosion rate in buffered acidic and alkaline electrolytes due to pH- and temperature-dependent corrosion product precipitation. Observations were supported by electrochemical, SEM, and EDS observations. Due to the complexity of corrosion data, a reliable corrosion prediction based on empirical observations could be challenging. Artificial neural network (ANN) modeling was used for corrosion data pattern recognition by mimicking human neural network systems. Predictive models were developed based on corrosion data acquired in this study. The model was adaptable through iteratively update its prediction by error minimization during the training phase. Trained ANN model can predict uniform corrosion successfully. In addition to ANN, fuzzy curve analysis was utilized to rank the influence of each input (temperature, pH, Cl-, and time). For example, temperature and pH were found to be the most influential parameters to uniform corrosion. This information can provide feedback for ANN improvement, also known as "data pruning".

Degradation characteristics of polylactide in thermophilic anaerobic digestion with hyperthermophilic solubilization condition.

PubMed

Wang, F; Hidaka, T; Oishi, T; Osumi, S; Tsubota, J; Tsuno, H

2011-01-01

To test whether hyperthermophilic treatment promotes polylactide (PLA) dissolution and methane conversion under anaerobic digestion conditions, a single thermophilic control reactor (55 °C) and a two-phase system consisting of a hyperthermophilic reactor (80 °C) and a thermophilic reactor (55 °C) were continuously fed with a mixture of PLA and artificial kitchen garbage. In Runs 1 and 2, the PLA dissolution ratios in the two-phase system were 79.2 ± 6.5% and 85.2 ± 7.0%, respectively, higher than those of the control. Batch experimental results indicated that hyperthermophilic treatment could promote PLA dissolution to a greater degree as compared with single thermophilic treatment and that ammonia addition also had a promotional effect on PLA dissolution. In the two-phase system, after hyperthermophilic treatment, dissolved PLA was converted to methane gas under the subsequent thermophilic condition.

Porous aerosil loading probucol using supercritical carbon dioxide: preparation, in vitro and in vivo characteristics.

PubMed

Chu, Chunxia; Liu, Muhua; Wang, Dongmei; Guan, Jibin; Cai, Cuifang; Sun, Yuanpeng; Zhang, Tianhong

2014-06-01

The aim of this study was to enhance the dissolution rate and oral bioavailability of probucol. Probucol was adsorbed onto aerosils via supercritical carbon dioxide (ScCO2) and the physicochemistry properties of probucol-aerosil powder were evaluated by differential scanning calorimetry, X-ray diffraction, infrared spectroscopy and scanning electron microscopy. Tablets of the probucol-aerosil powder were prepared by direct compression method. In the dissolution test, the probucol-aerosil tablets showed a significant enhanced dissolution rate compared with commercial tablets. Bioavailability study was carried out in beagle dogs. Probucol-aerosil tablets exhibited higher AUC and Cmax than commercial tablets. The improved dissolution and bioavailability of probucol-aerosil tablets were attributed to the amorphous state and good dispersion of probucol. It is a feasible method to enhance the oral bioavailability by adsorbing probucol onto aerosils via ScCO2.

Antisolvent crystallization of a cardiotonic drug in ionic liquids: Effect of mixing on the crystal properties

NASA Astrophysics Data System (ADS)

de Azevedo Jacqueline, Resende; Fabienne, Espitalier; Jean-Jacques, Letourneau; Inês, Ré Maria

2017-08-01

LASSBio-294 (3,4-methylenedioxybenzoyl-2-thienylhydrazon) is a poorly soluble drug which has been proposed to have major advantages over other cardiotonic drugs. Poorly water soluble drugs present limited bioavailability due to their low solubility and dissolution rate. An antisolvent crystallization processing can improve the dissolution rate by decreasing the crystals particle size. However, LASSBio-294 is also poorly soluble in organic solvents and this operation is limited. In order to open new perspectives to improve dissolution rate, this work has investigated LASSBio-294 in terms of its antisolvent crystallization in 1-ethyl-3-methylimidazolium methyl phosphonate [emim][CH3O(H)PO2] as solvent and water as antisolvent. Two modes of mixing are tested in stirred vessel with different pre-mixers (Roughton or T-mixers) in order to investigate the mixing effect on the crystal properties (crystalline structure, particle size distribution, residual solvent and in vitro dissolution rate). Smaller drug particles with unchanged crystalline structure were obtained. Despite the decrease of the elementary particles size, the recrystallized particles did not achieve a better dissolution profile. However, this study was able to highlight a certain number of findings such as the impact of the hydrodynamic conditions on the crystals formation and the presence of a gel phase limiting the dissolution rate.

Groundwater flow and its effect on salt dissolution in Gypsum Canyon watershed, Paradox Basin, southeast Utah, USA

NASA Astrophysics Data System (ADS)

Reitman, Nadine G.; Ge, Shemin; Mueller, Karl

2014-09-01

Groundwater flow is an important control on subsurface evaporite (salt) dissolution. Salt dissolution can drive faulting and associated subsidence on the land surface and increase salinity in groundwater. This study aims to understand the groundwater flow system of Gypsum Canyon watershed in the Paradox Basin, Utah, USA, and whether or not groundwater-driven dissolution affects surface deformation. The work characterizes the groundwater flow and solute transport systems of the watershed using a three-dimensional (3D) finite element flow and transport model, SUTRA. Spring samples were analyzed for stable isotopes of water and total dissolved solids. Spring water and hydraulic conductivity data provide constraints for model parameters. Model results indicate that regional groundwater flow is to the northwest towards the Colorado River, and shallow flow systems are influenced by topography. The low permeability obtained from laboratory tests is inconsistent with field observed discharges, supporting the notion that fracture permeability plays a significant role in controlling groundwater flow. Model output implies that groundwater-driven dissolution is small on average, and cannot account for volume changes in the evaporite deposits that could cause surface deformation, but it is speculated that dissolution may be highly localized and/or weaken evaporite deposits, and could lead to surface deformation over time.

Role of fiber dissolution in biological activity in rats.

PubMed

Eastes, W; Hadley, J G

1994-12-01

This report deals with the role of dissolution in removing long fibers from the lung and with a mathematical model that predicts chronic effects in rats following inhalation or intraperitoneal (i.p.) injection of fibers. Results of intratracheal instillation studies and inhalation studies in rats demonstrate clearly that long vitreous fibers dissolve in vivo at about the same rate measured in vitro in fluid designed to stimulate the extracellular lung fluid. For the glass, rock, and slag wool fibers tested, dissolution removed most of the fibers longer than 20 microns inhaled into the rats' lungs within 6 months after both short-term (5 days) and long-term (1 to 2 years) exposures. A mathematical model was developed that is based on fiber dissolution and allows one to predict the development of chronic lung diseases in rats. The model predicted the incidence of fibrosis and lung tumors in a series of recent inhalation studies and tumors following ip injection to within about the error of the experiments. The model suggests that all fibers, regardless of their dissolution rate in lung fluid, can produce tumors after ip injection because the dose can be unlimited by this route. After inhalation, in contrast, dissolution of many types of long vitreous fibers occurs rapidly, and disease does not ensue for these fibers.

MRI as a tool for evaluation of oral controlled release dosage forms.

PubMed

Dorożyński, Przemysław P; Kulinowski, Piotr; Młynarczyk, Anna; Stanisz, Greg J

2012-02-01

The magnetic resonance imaging (MRI) studies of controlled-release (CR) dosage forms can be roughly divided into two groups. The first comprises studies performed in static conditions (small solvent volumes and ambient temperature). Such studies have provided insight into molecular phenomena in hydrating polymeric matrices. The second group covers research performed in dynamic conditions (medium flow or stirring) related to drug dissolution. An important issue is supplementation of the MRI results with data obtained by complementary techniques, such as X-ray microtomography (μCT). As we discuss here, an understanding of the mechanism underlying the release of the drug from the dosage form will lead to the development of detailed, molecularly defined, CR dosage forms. Copyright © 2011 Elsevier Ltd. All rights reserved.

34. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF BLOCKHOUSE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

34. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF BLOCKHOUSE AND TOP OF TEST BAY, LOOKING NORTHEAST - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

33. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF BLOCKHOUSE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

33. 100,000 POUND STATIC TEST FACILITY: GENERAL VIEW OF BLOCKHOUSE AND UPPER LEVEL OF TEST BAY, LOOKING NORTH - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

Technical Evaluation Motor No. 7 (TEM-7)

NASA Technical Reports Server (NTRS)

Hughes, Phil

1991-01-01

The Technical Evaluation Motor No. 7 (TEM-7) test was a full-scale, full duration static test firing of a high performance motor-configuration solid rocket motor with nozzle vectoring. The final test report documents the procedures, performance, and results of the static test firing of TEM-7. All observations, discussions, conclusions, and recommendations included in the report are complete and final except for the TEM-7 fixed housing unbond investigation. A presentation and discussion of TEM-7 performance, anomalies, and test result concurrence with the objectives outlined in CTP-0107, Rev A, Space Shuttle Technical Evaluation Motor No. 7 (TEM-7) Static Fire Test Plan are included.

Interaction of HEPES buffer with glass-ceramic scaffold: Can HEPES replace TRIS in SBF?

PubMed

Rohanová, Dana; Horkavcová, Diana; Paidere, Laine; Boccaccini, Aldo Roberto; Bozděchová, Pavlína; Bezdička, Petr

2018-01-01

An international standard (ISO: 23317:2014) exists for the in vitro testing of inorganic biomaterials in simulated body fluid (SBF). This standard uses TRIS buffer to maintain neutral pH in SBF, but in our previous paper, we showed that the interaction of a tested glass-ceramic material with TRIS can produce false-positive results. In this study, we evaluated whether the HEPES buffer, which also belongs to the group of Good´s buffers, would be more suitable for SBF. We compared its suitability in two media: SBF with HEPES and demineralized water with HEPES. The tested scaffold (45S5 bioactive glass-based) was exposed to the media under a static-dynamic arrangement (solutions were replaced on a daily basis) for 15 days. Leachate samples were collected daily for the analysis of Ca 2+ ions and Si (AAS), (PO 4 ) 3- ions (UV-VIS), and to measure pH. The glass-ceramic scaffold was analyzed by SEM/EDS, XRD, and WD-XRF before and after 0.3, 1, 3, 7, 11, and 15 days of exposure. Our results confirmed the rapid selective dissolution of the glass-ceramic crystalline phase (Combeite) containing Ca 2+ ions due to the presence of HEPES, hydroxyapatite supersaturation being reached within 24 h in both solutions. These new results suggest that, like TRIS, HEPES buffer is not suitable for the in vitro testing of highly reactive inorganic biomaterials (glass, glass-ceramics). The ISO standard for such tests requires revision, but HEPES is not a viable alternative to TRIS buffer. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 143-152, 2018. © 2016 Wiley Periodicals, Inc.

30 CFR 18.67 - Static-pressure tests.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Static-pressure tests. 18.67 Section 18.67 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR TESTING, EVALUATION, AND APPROVAL OF MINING PRODUCTS ELECTRIC MOTOR-DRIVEN MINE EQUIPMENT AND ACCESSORIES Inspections and Tests § 18...

A dissolution model that accounts for coverage of mineral surfaces by precipitation in core floods

NASA Astrophysics Data System (ADS)

Pedersen, Janne; Jettestuen, Espen; Madland, Merete V.; Hildebrand-Habel, Tania; Korsnes, Reidar I.; Vinningland, Jan Ludvig; Hiorth, Aksel

2016-01-01

In this paper, we propose a model for evolution of reactive surface area of minerals due to surface coverage by precipitating minerals. The model is used to interpret results from an experiment where a chalk core was flooded with MgCl2 for 1072 days, giving rise to calcite dissolution and magnesite precipitation. The model successfully describes both the long-term behavior of the measured effluent concentrations and the more or less homogeneous distribution of magnesite found in the core after 1072 days. The model also predicts that precipitating magnesite minerals form as larger crystals or aggregates of smaller size crystals, and not as thin flakes or as a monomolecular layer. Using rate constants obtained from literature gave numerical effluent concentrations that diverged from observed values only after a few days of flooding. To match the simulations to the experimental data after approximately 1 year of flooding, a rate constant that is four orders of magnitude lower than reported by powder experiments had to be used. We argue that a static rate constant is not sufficient to describe a chalk core flooding experiment lasting for nearly 3 years. The model is a necessary extension of standard rate equations in order to describe long term core flooding experiments where there is a large degree of textural alteration.

[Efficient Pharmaceutical Formulation Designs and Their Development Using Mathematical and Statistical Analysis].

PubMed

Iwao, Yasunori

2015-01-01

With the aim of directly predicting the functionality and mechanism of pharmaceutical excipients, we investigated an analysis method based on available surface area (S(t)), which is the surface area of a drug in direct contact with the external solvent during dissolution. First, to study the effect of lubricant concentration on the dissolution rate of acetaminophen (APAP), the dissolution behaviors as well as the change over time in S(t) of APAP tablets were examined. In the dissolution tests, a retarded dissolution of APAP was not observed with new lubricant triglycerin full behenate (TR-FB), whereas magnesium stearate (Mg-St) retarded the dissolution. The S(t) profiles for APAP with Mg-St at>0.5% showed downward curvature indicating a gradual decrease in surface area over time. Conversely, with TR-FB, even when its concentration was increased, the S(t) profile for APAP had a maximum value. The differences between Mg-St and TR-FB could be explained by the differences in extensibility deriving from their morphology. Next, we evaluated the effect of disintegtant concentration using five disintegrants. When disintegrant was added to ethenzamide tablet formulation, an increase in the dissolution rate and S(t) dependent on disintegrant concentration was observed, according to the type of disintegrant. It was found that the water absorption ability of disintegrants had strong correlations with the parameters of S(t). Taken together, this study demonstrates that analysis of S(t) can directly provide useful information, especially about the functionality of pharmaceutical excipients.

Defining level A IVIVC dissolution specifications based on individual in vitro dissolution profiles of a controlled release formulation.

PubMed

González-García, I; García-Arieta, A; Merino-Sanjuan, M; Mangas-Sanjuan, V; Bermejo, M

2018-07-01

Regulatory guidelines recommend that, when a level A IVIVC is established, dissolution specification should be established using averaged data and the maximum difference between AUC and C max between the reference and test formulations cannot be greater than 20%. However, averaging data assumes a loss of information and may reflect a bias in the results. The objective of the current work is to present a new approach to establish dissolution specifications using a new methodology (individual approach) instead of average data (classical approach). Different scenarios were established based on the relationship between in vitro-in vivo dissolution rate coefficient using a level A IVIVC of a controlled release formulation. Then, in order to compare this new approach with the classical one, six additional batches were simulated. For each batch, 1000 simulations of a dissolution assay were run. C max ratios between the reference formulation and each batch were calculated showing that the individual approach was more sensitive and able to detect differences between the reference and the batch formulation compared to the classical approach. Additionally, the new methodology displays wider dissolution specification limits than the classical approach, ensuring that any tablet from the new batch would generate in vivo profiles which its AUC or C max ratio will be out of the 0.8-1.25 range, taking into account the in vitro and in vivo variability of the new batches developed. Copyright © 2018 Elsevier B.V. All rights reserved.

Understanding the Effects of Dissolution on the Mg/Ca Paleothermometer in Planktic Foraminifera: Evidence From a Novel Individual Foraminifera Method

NASA Astrophysics Data System (ADS)

Rongstad, Brigitta L.; Marchitto, Thomas M.; Herguera, Juan Carlos

2017-12-01

It is well documented that partial dissolution of planktic foraminiferal tests results in a reduction of Mg/Ca ratios, and hence of inferred calcification temperatures; however, traditional analysis techniques have made it difficult to identify the exact mechanism through which Mg is lost. Three hypotheses have been proposed as models for Mg loss for a given extent of dissolution: (1) a percent loss of Mg in individuals, (2) a molar loss of Mg in individuals, and (3) a loss of the highest-Mg (warmest) individuals from a population. It is vital to better constrain these models as they have very different implications for Mg/Ca paleotemperature dissolution corrections. Here we use a novel individual foraminifera Mg/Ca method to examine the effects of dissolution on the Mg/Ca paleothermometer in three species of planktic foraminifera, Globigerinoides ruber, Neogloboquadrina dutertrei, and Pulleniatina obliquiloculata, from a depth transect of core tops on the Ontong Java Plateau in the western equatorial Pacific. With the exception of the most heavily dissolved population of P. obliquiloculata, our data best support a percent Mg loss model as indicated by the preservation of inferred temperature distribution shapes among the sampled populations and the close fit of the simulated percent Mg loss model to the observed data. Coupled with estimates for foraminiferal dissolution, identification of the percent Mg loss model will allow for more accurate dissolution corrections in Mg/Ca paleothermometry work.

A comparison of the effect of temperature and moisture on the solid dispersions: aging and crystallization.

PubMed

Tian, Bin; Zhang, Ling; Pan, Zhendong; Gou, Jingxin; Zhang, Yu; Tang, Xing

2014-11-20

The purpose of this work was to compare the effect of temperature and relative humidity (RH) on the physical stability and dissolution of solid dispersions. Cinnarizine-Soluplus(®) solid dispersions (SDs) at three different drug loadings (10, 20 and 35 wt%) were prepared by hot melt extrusion and exposed to stress conditions: high temperatures (40 and 60 °C), high relative humidities (75% and 94% RH) and accelerated conditions (40 °C/75% RH) for 30 days, or stored at 25 °C for up to 5 months. Changes in solid state and dissolution of SDs were investigated by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and dissolution testing. For samples under stress conditions, the results showed a reduced dissolution and a recrystallization of the drug with an increased crystallinity in the order of 40 °C/75% RH, >60 °C/0% RH, >25 °C/94% RH, >40 °C/0% RH, >25 °C/75% RH. For samples stored at 25 °C, nonlinear physical aging was observed and the dissolution also decreased although the SDs were still amorphous. The results indicated that temperature and humidity seemed to have comparable effects on the crystallization of cinnarizine-Soluplus(®) SDs. It is not reasonable to regard recrystallization as a sign of reduced dissolution, and glass transition temperature (Tg) may be a good indicator of the changes in dissolution. Copyright © 2014 Elsevier B.V. All rights reserved.

Interlaboratory studies on in vitro test methods for estimating in vivo resorption of calcium phosphate ceramics.

PubMed

Ito, Atsuo; Sogo, Yu; Yamazaki, Atsushi; Aizawa, Mamoru; Osaka, Akiyoshi; Hayakawa, Satoshi; Kikuchi, Masanori; Yamashita, Kimihiro; Tanaka, Yumi; Tadokoro, Mika; de Sena, Lídia Ágata; Buchanan, Fraser; Ohgushi, Hajime; Bohner, Marc

2015-10-01

A potential standard method for measuring the relative dissolution rate to estimate the resorbability of calcium-phosphate-based ceramics is proposed. Tricalcium phosphate (TCP), magnesium-substituted TCP (MgTCP) and zinc-substituted TCP (ZnTCP) were dissolved in a buffer solution free of calcium and phosphate ions at pH 4.0, 5.5 or 7.3 at nine research centers. Relative values of the initial dissolution rate (relative dissolution rates) were in good agreement among the centers. The relative dissolution rate coincided with the relative volume of resorption pits of ZnTCP in vitro. The relative dissolution rate coincided with the relative resorbed volume in vivo in the case of comparison between microporous MgTCPs with different Mg contents and similar porosity. However, the relative dissolution rate was in poor agreement with the relative resorbed volume in vivo in the case of comparison between microporous TCP and MgTCP due to the superimposition of the Mg-mediated decrease in TCP solubility on the Mg-mediated increase in the amount of resorption. An unambiguous conclusion could not be made as to whether the relative dissolution rate is predictive of the relative resorbed volume in vivo in the case of comparison between TCPs with different porosity. The relative dissolution rate may be useful for predicting the relative amount of resorption for calcium-phosphate-based ceramics having different solubility under the condition that the differences in the materials compared have little impact on the resorption process such as the number and activity of resorbing cells. The evaluation and subsequent optimization of the resorbability of calcium phosphate are crucial in the use of resorbable calcium phosphates. Although the resorbability of calcium phosphates has usually been evaluated in vivo, establishment of a standard in vitro method that can predict in vivo resorption is beneficial for accelerating development and commercialization of new resorbable calcium phosphate materials as well as reducing use of animals. However, there are only a few studies to propose such an in vitro method within which direct comparison was carried out between in vitro and in vivo resorption. We propose here an in vitro method based on measuring dissolution rate. The efficacy and limitations of the method were evaluated by international round-robin tests as well as comparison with in vivo resorption studies for future standardization. This study was carried out as one of Versailles Projects on Advanced Materials and Standards (VAMAS). Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

33. VIEW LOOKING SOUTH AT THE STATIC TEST TOWER DURING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

33. VIEW LOOKING SOUTH AT THE STATIC TEST TOWER DURING A TEST OF THE PROPULSION SYSTEM OF A JUPITER MISSILE. DATE AND PHOTOGRAPHER UNKNOWN. FRED ORDWAY COLLECTION, U.S. SPACE AND ROCKET CENTER, HUNTSVILLE, AL. - Marshall Space Flight Center, Saturn Propulsion & Structural Test Facility, East Test Area, Huntsville, Madison County, AL

Low temperature-pressure batch experiments and field push-pull tests: Assessing potential effects of an unintended CO2 release from CCUS projects on groundwater chemistry

NASA Astrophysics Data System (ADS)

Mickler, P. J.; Yang, C.; Lu, J.; Reedy, R. C.; Scanlon, B. R.

2012-12-01

Carbon Capture Utilization and Storage projects (CCUS), where CO2 is captured at point sources such as power stations and compressed into a supercritical liquid for underground storage, has been proposed to reduce atmospheric CO2 and mitigate global climate change. Problems may arise from CO2 releases along discreet pathways such as abandoned wells and faults, upwards and into near surface groundwater. Migrating CO2 may inversely impact fresh water resources by increasing mineral solubility and dissolution rates and mobilizing harmful trace elements including As and Pb. This study addresses the impacts on fresh water resources through a combination of laboratory batch experiments, where aquifer sediment are reacted in their corresponding groundwater in 100% CO2 environments, and field push-pull tests where groundwater is equilibrated with 100% CO2, reacted in-situ in the groundwater system, and pulled out for analyses. Batch experiments were performed on aquifer material from carbonate dominated, mixed carbonate/silicalstic, and siliclastic dominated systems. A mixed silicalstic/carbonate system was chosen for the field based push-pull test. Batch experiment results suggest carbonate dissolution increased the concentration of Ca, Mg, Sr, Ba, Mn, U and HCO3- in groundwater. In systems with significant carbonate content, dissolution continued until carbonate saturation was achieved at approximately 1000 hr. Silicate dissolution increased the conc. of Si, K Ni and Co, but at much lower rates than carbonate dissolution. The elements As, Mo, V, Zn, Se and Cd generally show similar behavior where concentrations initially increase but soon drop to levels at or below the background concentrations (~48 hours). A Push-Pull test on one aquifer system produced similar geochemical behavior but observed reaction rates are higher in batch experiments relative to push-pull tests. Release of CO2 from CCUS sites into overlying aquifer systems may adversely impact groundwater quality primarily through carbonate dissolution which releases Ca and elements that substitute for Ca in crystal lattices. Silicate weathering releases primarily Si and K at lower rates. Chemical changes with the addition of CO2 may initially mobilize As, Mo, V, Zn, Se and Cd but these elements become immobile in the lowered pH water and sorb onto aquifer minerals. A combined laboratory batch experiment and field push-pull test in fresh water aquifers overlying CCUS projects will best characterize the response of the aquifer to increased pCO2. The long experimental duration of the batch experiments may allow reactions to reach equilibrium however; reaction rates may be artificially high due to increased mineral surface areas. Field based push-pull tests offer a more realistic water rock ratio and test a much larger volume of aquifer material but the test must be shorter in duration because the high pCO2 water is subject to mixing with low pCO2 background water and migration away from the test well with groundwater flow. A comparison of the two methods best characterizes the potential effects on groundwater chemistry

Deep flaws in weldments of aluminum and titanium

NASA Technical Reports Server (NTRS)

Masters, J. N.; Engstrom, W. L.; Bixler, W. D.

1974-01-01

Surface flawed specimens of 2219-T87 and 6Al-4V STA titanium weldments were tested to determine static failure modes, failure strength, and fatigue flaw growth characteristics. Thicknesses selected for this study were purposely set at values where, for most test conditions, abrupt instability of the flaw at fracture would not be expected. Static tests for the aluminum weldments were performed at room, LN2 and LH2 temperatures. Titanium static tests for tests were performed at room and LH2 temperatures. Results of the static tests were used to plot curves relating initial flaw size to leakage- or failure-stresses (i.e. "failure" locus curves). Cyclic tests, for both materials, were then performed at room temperature, using initial flaws only slightly below the previously established failure locus for typical proof stress levels. Cyclic testing was performed on pairs of specimens, one with and one without a simulated proof test cycle. Comparisons were made then to determine the value and effect of proof testing as affected by the various variables of proof and operating stress, flaw shape, material thickness, and alloy.

40 CFR 53.65 - Test procedure: Loading test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... performing the test in § 53.62 (full wind tunnel test), § 53.63 (wind tunnel inlet aspiration test), or § 53... particle delivery system shall consist of a static chamber or a low velocity wind tunnel having a.... The mean velocity in the test section of the static chamber or wind tunnel shall not exceed 2 km/hr...

Hydrothermal Alteration of Glass from Underground Nuclear Tests: Formation and Transport of Pu-clay Colloids at the Nevada National Security Site

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

Zavarin, M.; Zhao, P.; Joseph, C.

2015-05-27

The testing of nuclear weapons at the Nevada National Security Site (NNSS), formerly the Nevada Test Site (NTS), has led to the deposition of substantial quantities of plutonium into the environment. Approximately 2.8 metric tons (3.1×10 4 TBq) of Pu were deposited in the NNSS subsurface as a result of underground nuclear testing. While 3H is the most abundant anthropogenic radionuclide deposited in the NNSS subsurface (4.7×10 6 TBq), plutonium is the most abundant from a molar standpoint. The only radioactive elements in greater molar abundance are the naturally occurring K, Th, and U isotopes. 239Pu and 240Pu represent themore » majority of alpha-emitting Pu isotopes. The extreme temperatures associated with underground nuclear tests and the refractory nature of Pu results in most of the Pu (98%) being sequestered in melted rock, referred to as nuclear melt glass (Iaea, 1998). As a result, Pu release to groundwater is controlled, in large part, by the leaching (or dissolution) of nuclear melt glass over time. The factors affecting glass dissolution rates have been studied extensively. The dissolution of Pu-containing borosilicate nuclear waste glasses at 90ºC has been shown to lead to the formation of dioctahedral smectite colloids. Colloid-facilitated transport of Pu at the NNSS has been observed. Recent groundwater samples collected from a number of contaminated wells have yielded a wide range of Pu concentrations from 0.00022 to 2.0 Bq/L. While Pu concentrations tend to fall below the Maximum Contaminant Level (MCL) established by the Environmental Protection Agency (EPA) for drinking water (0.56 Bq/L), we do not yet understand what factors limit the Pu concentration or its transport behavior. To quantify the upper limit of Pu concentrations produced as a result of melt glass dissolution and determine the nature of colloids and Pu associations, we performed a 3 year nuclear melt glass dissolution experiment across a range of temperatures (25-200 °C) that represent hydrothermal conditions representative of the underground nuclear test cavities (when groundwater has re-saturated the nuclear melt glass and glass dissolution occurs). Colloid loads and Pu concentrations were monitored along with the mineralogy of both the colloids and the secondary mineral phases. The intent was to establish an upper limit for Pu concentrations at the NNSS, provide context regarding the Pu concentrations observed at the NNSS to date and the Pu concentrations that may be observed in the future. The results provide a conceptual model for the risks posed by Pu migration at the NNSS.« less

Saturn Apollo Program

NASA Image and Video Library

1963-12-05

The test laboratory of the Marshall Space Flight Center (MSFC) tested the F-1 engine, the most powerful rocket engine ever fired at MSFC. The engine was tested on the newly modified Saturn IB Static Test Stand which had been used for three years to test the Saturn I eight-engine booster, S-I (first) stage. In 1961 the test stand was modified to permit static firing of the S-I/S-IB stage and the name of the stand was then changed to the S-IB Static Test Stand. Producing a combined thrust of 7,500,000 pounds, five F-1 engines powered the S-IC (first) stage of the Saturn V vehicle for the marned lunar mission.

Saturn Apollo Program

NASA Image and Video Library

1963-12-01

The test laboratory of the Marshall Space Flight Center (MSFC) tested the F-1 engine, the most powerful rocket engine ever fired at MSFC. The engine was tested on the newly modified Saturn IB static test stand that had been used for three years to test the Saturn I eight-engine booster, S-I (first) stage. In 1961, the test stand was modified to permit static firing of the S-I/S-IB stage and the name of the stand was then changed to the S-IB Static Test Stand. Producing a combined thrust of 7,500,000 pounds, five F-1 engines powered the S-IC (first) stage of the Saturn V vehicle for the marned lunar mission.

The role of visual representation in physics learning: dynamic versus static visualization

NASA Astrophysics Data System (ADS)

Suyatna, Agus; Anggraini, Dian; Agustina, Dina; Widyastuti, Dini

2017-11-01

This study aims to examine the role of visual representation in physics learning and to compare the learning outcomes of using dynamic and static visualization media. The study was conducted using quasi-experiment with Pretest-Posttest Control Group Design. The samples of this research are students of six classes at State Senior High School in Lampung Province. The experimental class received a learning using dynamic visualization and control class using static visualization media. Both classes are given pre-test and post-test with the same instruments. Data were tested with N-gain analysis, normality test, homogeneity test and mean difference test. The results showed that there was a significant increase of mean (N-Gain) learning outcomes (p <0.05) in both experimental and control classes. The averages of students’ learning outcomes who are using dynamic visualization media are significantly higher than the class that obtains learning by using static visualization media. It can be seen from the characteristics of visual representation; each visualization provides different understanding support for the students. Dynamic visual media is more suitable for explaining material related to movement or describing a process, whereas static visual media is appropriately used for non-moving physical phenomena and requires long-term observation.

Commuter rail seat testing and analysis of facing seats

DOT National Transportation Integrated Search

2003-12-01

Tests have been conducted on the Bombardier back-to-back commuter rail car seat in a facing-seat configuration to evaluate its performance under static and dynamic loading conditions. Quasi-static tests have been conducted to establish the load defle...

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

Neeway, James J.; Rieke, Peter C.; Parruzot, Benjamin P.

In far-from-equilibrium conditions, the dissolution of borosilicate glasses used to immobilize nuclear waste is known to be a function of both temperature and pH. The aim of this paper is to study effects of these variables on three model waste glasses (SON68, ISG, AFCI). To do this, experiments were conducted at temperatures of 23, 40, 70, and 90 °C and pH(RT) values of 9, 10, 11, and 12 with the single-pass flow-through (SPFT) test method. The results from these tests were then used to parameterize a kinetic rate model based on transition state theory. Both the absolute dissolution rates andmore » the rate model parameters are compared with previous results. Discrepancies in the absolute dissolution rates as compared to those obtained using other test methods are discussed. Rate model parameters for the three glasses studied here are nearly equivalent within error and in relative agreement with previous studies. The results were analyzed with a linear multivariate regression (LMR) and a nonlinear multivariate regression performed with the use of the Glass Corrosion Modeling Tool (GCMT), which is capable of providing a robust uncertainty analysis. This robust analysis highlights the high degree of correlation of various parameters in the kinetic rate model. As more data are obtained on borosilicate glasses with varying compositions, the effect of glass composition on the rate parameter values could possibly be obtained. This would allow for the possibility of predicting the forward dissolution rate of glass based solely on composition« less

Setting accelerated dissolution test for PLGA microspheres containing peptide, investigation of critical parameters affecting drug release rate and mechanism.

PubMed

Tomic, I; Vidis-Millward, A; Mueller-Zsigmondy, M; Cardot, J-M

2016-05-30

The objective of this study was development of accelerated in vitro release method for peptide loaded PLGA microspheres using flow-through apparatus and assessment of the effect of dissolution parameters (pH, temperature, medium composition) on drug release rate and mechanism. Accelerated release conditions were set as pH 2 and 45°C, in phosphate buffer saline (PBS) 0.02M. When the pH was changed from 2 to 4, diffusion controlled phases (burst and lag) were not affected, while release rate during erosion phase decreased two-fold due to slower ester bonds hydrolyses. Decreasing temperature from 45°C to 40°C, release rate showed three-fold deceleration without significant change in release mechanism. Effect of medium composition on drug release was tested in PBS 0.01M (200 mOsm/kg) and PBS 0.01M with glucose (380 mOsm/kg). Buffer concentration significantly affected drug release rate and mechanism due to the change in osmotic pressure, while ionic strength did not have any effect on peptide release. Furthermore, dialysis sac and sample-and-separate techniques were used, in order to evaluate significance of dissolution technique choice on the release process. After fitting obtained data to different mathematical models, flow-through method was confirmed as the most appropriate for accelerated in vitro dissolution testing for a given formulation. Copyright © 2016 Elsevier B.V. All rights reserved.

ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems.

PubMed

Thomas, Dennis G; Smith, Jordan N; Thrall, Brian D; Baer, Donald R; Jolley, Hadley; Munusamy, Prabhakaran; Kodali, Vamsi; Demokritou, Philip; Cohen, Joel; Teeguarden, Justin G

2018-01-25

The development of particokinetic models describing the delivery of insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems has improved the basis for dose-response analysis, hazard ranking from high-throughput systems, and now allows for translation of exposures across in vitro and in vivo test systems. Complimentary particokinetic models that address processes controlling delivery of both particles and released ions to cells, and the influence of particle size changes from dissolution on particle delivery for cell-culture systems would help advance our understanding of the role of particles and ion dosimetry on cellular toxicology. We developed ISD3, an extension of our previously published model for insoluble particles, by deriving a specific formulation of the Population Balance Equation for soluble particles. ISD3 describes the time, concentration and particle size dependent dissolution of particles, their delivery to cells, and the delivery and uptake of ions to cells in in vitro liquid test systems. We applied the model to calculate the particle and ion dosimetry of nanosilver and silver ions in vitro after calibration of two empirical models, one for particle dissolution and one for ion uptake. Total media ion concentration, particle concentration and total cell-associated silver time-courses were well described by the model, across 2 concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution data for 20 nm particles as a function of serum protein concentration, but successfully described the media and cell dosimetry time-course for both particles at all concentrations and time points. We also report the finding that protein content in media affects the initial rate of dissolution and the resulting near-steady state ion concentration in solution for the systems we have studied. By combining experiments and modeling, we were able to quantify the influence of proteins on silver particle solubility, determine the relative amounts of silver ions and particles in exposed cells, and demonstrate the influence of particle size changes resulting from dissolution on particle delivery to cells in culture. ISD3 is modular and can be adapted to new applications by replacing descriptions of dissolution, sedimentation and boundary conditions with those appropriate for particles other than silver.

Evolution of Abnormally Low Pressure at Bravo Dome and its Implications for Carbon Capture and Storage (CCS)

NASA Astrophysics Data System (ADS)

Akhbari, D.; Hesse, M. A.

2015-12-01

Carbon capture and storage allows reductions of the rapidly rising CO2 from fossil fuel-based power generation, if large storage rates and capacities can be achieved. The injection of large fluid volumes at high rates leads to a build-up of pore-pressure in the storage formation that may induce seismicity and compromise the storage security. Many natural CO2 fields in midcontinent US, in contrast, are under-pressured rather than over-pressured suggesting that natural processes reduce initial over-pressures and generate significant under-pressures. The question is therefore to understand the sequence of process(es) that allow the initial over-pressure to be eliminated and the under-pressure to be maintained over geological periods of time. We therefore look into pressure evolution in Bravo Dome, one of the largest natural CO2 accumulations in North America, which stores 1.3 Gt of CO2. Bravo Dome is only 580-900 m deep and is divided into several compartments with near gas-static pressure (see Figure). The pre-production gas pressures in the two main compartments that account for 70% of the mass of CO2 stored at Bravo Dome are more than 6 MPa below hydrostatic pressure. Here we show that the under-pressure in the Bravo Dome CO2 reservoir is maintained by hydrological compartmentalization over millennial timescales and generated by a combination of processes including cooling, erosional unloading, limited leakage into overlying formations, and CO2 dissolution into brine. Herein, we introduce CO2 dissolution into brine as a new process that reduce gas pressure in a compartmentalized reservoir and our results suggest that it may contribute significantly to reduce the initial pressure build-up due to injection. Bravo Dome is the first documented case of pressure drop due to CO2 dissolution. To have an accurate prediction of pressure evolution in Bravo Dome, our models must include geomechanics and thermodynamics for the reservoir while they account for the pressure changes due to the CO2 dissolution.

In vitro dissolution of uranium oxide by baboon alveolar macrophages.

PubMed Central

Poncy, J L; Metivier, H; Dhilly, M; Verry, M; Masse, R

1992-01-01

In vitro cellular dissolution tests for insoluble forms of uranium oxide are technically difficult with conventional methodology using adherent alveolar macrophages. The limited number of cells per flask and the slow dissolution rate in a large volume of nutritive medium are obvious restricting factors. Macrophages in suspension cannot be substituted because they represent different and poorly reproducible functional subtypes with regard to activation and enzyme secretion. Preliminary results on the dissolution of uranium oxide using immobilized alveolar macrophages are promising because large numbers of highly functional macrophages can be cultured in a limited volume. Cells were obtained by bronchoalveolar lavages performed on baboons (Papio papio) and then immobilized after the phagocytosis of uranium octoxide (U3O8) particles in alginate beads linked with Ca2+. The dissolution rate expressed as percentage of initial uranium content in cells was 0.039 +/- 0.016%/day for particles with a count median geometric diameter of 3.84 microns(sigma g = 1.84). A 2-fold increase in the dissolution rate was observed when the same number of particles was immobilized without macrophages. These results, obtained in vitro, suggest that the U3O8 preparation investigated should be assigned to inhalation class Y as recommended by the International Commission on Radiological Protection. Future experiments are intended to clarify this preliminary work and to examine the dissolution characteristics of other particles such as uranium dioxide. It is recommended that the dissolution rate should be measured over an interval of 3 weeks, which is compatible with the survival time of immobilized cells in culture and may reveal transformation states occurring with aging of the particles. PMID:1396447

Evaluation of the in-flight noise signature of a 32-chute suppressor nozzle: Acoustic data report. [outdoor static and 40 x 80 ft. wind tunnel tests

NASA Technical Reports Server (NTRS)

Moore, M. T.; Doyle, V. L.

1977-01-01

Outdoor static and 40 x 80 FT wind tunnel tests of the J79-15 engine/nacelle system with the conic nozzle and 32-chute exhaust suppressor were conducted to acquire the data necessary to evaluate the simulated in-flight signature of an engine-size 32-chute exhaust nozzle suppressor using the 40 x 80 ft wind tunnel and to study possible engine core noise contamination of the jet signature. The tests are described and and a sampling of the data acquired is presented. Included are aero performance summaries, as-measured and composite 1/3 OBSPL spectra for the 70 ft sideline high and low mics from the outdoor static tests, sideline traverse spectra and internal noise measurements from both the outdoor static and the 40 x 80 ft wind tunnel tests.

Study of the influence of hole quality on composite materials

NASA Technical Reports Server (NTRS)

Pengra, J. J.

1980-01-01

The influence of hole quality on the structural behavior of composite materials was investigated. From an industry survey it was determined that the most frequent imperfections encountered during hole fabrication are chipout, delamination, and oversize conditions. These hole flaw types were generated in critical areas of static, compression, and fatigue specimens fabricated from T300/5208 graphite/epoxy system. The specimens were tested in static and cyclic pin bearing modes in addition to compression loading. Results of these tests are presented and discussed. The hole chipout defect reduced the static and cyclic endurance characteristics. Oversize holes also lowered the cyclic pin bearing endurance, but had no influence of the static pin bearing characteristics. Delamination had no insignificant influence on the static tension and cyclic pin bearing characteristics. Compression tests demonstrated a deleterious effect for chipout of delamination defects. Hole quality requirements proposed are discussed.

Crashworthiness testing of Amtrak's traditional coach seat : safety of high-speed ground transportation systems

DOT National Transportation Integrated Search

1996-10-01

Tests have been conducted on Amtrak's traditional passenger seat to evaluate its performance under static and dynamic loading conditions. Quasi-static tests have been conducted to establish the load-deflection characteristics of the seat. Dynamic tes...

Quantification of a maximum injection volume of CO2 to avert geomechanical perturbations using a compositional fluid flow reservoir simulator

NASA Astrophysics Data System (ADS)

Jung, Hojung; Singh, Gurpreet; Espinoza, D. Nicolas; Wheeler, Mary F.

2018-02-01

Subsurface CO2 injection and storage alters formation pressure. Changes of pore pressure may result in fault reactivation and hydraulic fracturing if the pressure exceeds the corresponding thresholds. Most simulation models predict such thresholds utilizing relatively homogeneous reservoir rock models and do not account for CO2 dissolution in the brine phase to calculate pore pressure evolution. This study presents an estimation of reservoir capacity in terms of allowable injection volume and rate utilizing the Frio CO2 injection site in the coast of the Gulf of Mexico as a case study. The work includes laboratory core testing, well-logging data analyses, and reservoir numerical simulation. We built a fine-scale reservoir model of the Frio pilot test in our in-house reservoir simulator IPARS (Integrated Parallel Accurate Reservoir Simulator). We first performed history matching of the pressure transient data of the Frio pilot test, and then used this history-matched reservoir model to investigate the effect of the CO2 dissolution into brine and predict the implications of larger CO2 injection volumes. Our simulation results -including CO2 dissolution- exhibited 33% lower pressure build-up relative to the simulation excluding dissolution. Capillary heterogeneity helps spread the CO2 plume and facilitate early breakthrough. Formation expansivity helps alleviate pore pressure build-up. Simulation results suggest that the injection schedule adopted during the actual pilot test very likely did not affect the mechanical integrity of the storage complex. Fault reactivation requires injection volumes of at least about sixty times larger than the actual injected volume at the same injection rate. Hydraulic fracturing necessitates much larger injection rates than the ones used in the Frio pilot test. Tested rock samples exhibit ductile deformation at in-situ effective stresses. Hence, we do not expect an increase of fault permeability in the Frio sand even in the presence of fault reactivation.

ISD3: a particokinetic model for predicting the combined effects of particle sedimentation, diffusion and dissolution on cellular dosimetry for in vitro systems

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

Thomas, Dennis G.; Smith, Jordan N.; Thrall, Brian D.

The development of particokinetic models describing the delivery of insoluble or poorly soluble nanoparticles to cells in liquid cell culture systems has improved the basis for dose-response analysis, hazard ranking from high-throughput systems, and now allows for translation of exposures across in vitro and in vivo test systems. Complimentary particokinetic models that address processes controlling delivery of both particles and released ions to cells, and the influence of particle size changes from dissolution on particle delivery for cell-culture systems would help advance our understanding of the role of particles ion dosimetry on cellular toxicology. We developed ISD3, an extension ofmore » our previously published model for insoluble particles, by deriving a specific formulation of the Population Balance Equation for soluble particles. ISD3 describes the time, concentration and particle size dependent dissolution of particles, their delivery to cells, and the delivery and uptake of ions to cells in in vitro liquid test systems. The model is modular, and can be adapted by application of any empirical model of dissolution, alternative approaches to calculating sedimentation rates, and cellular uptake or treatment of boundary conditions. We apply the model to calculate the particle and ion dosimetry of nanosilver and silver ions in vitro after calibration of two empirical models, one for particle dissolution and one for ion uptake. The results demonstrate utility and accuracy of the ISD3 framework for dosimetry in these systems. Total media ion concentration, particle concentration and total cell-associated silver time-courses were well described by the model, across 2 concentrations of 20 and 110 nm particles. ISD3 was calibrated to dissolution data for 20 nm particles as a function of serum protein concentration, but successfully described the media and cell dosimetry time-course for both particles at all concentrations and time points. We also report the finding that protein content in media has effects both on the initial rate of dissolution and the resulting near-steady state ion concentration in solution.« less

Corrosion of dental aluminium bronze in neutral saline and saline lactic acid.

PubMed

Tibballs, J E; Erimescu, Raluca

2006-09-01

To compare the corrosion behaviours of two aluminium bronze, dental casting alloys during a standard immersion test and for immersion in neutral saline. Cast specimens of aluminium bronzes with 1.4 wt% Fe (G) and 4 wt% Fe (N) were subject to progressively longer periods (up to in total 7 days) immersed in 0.1 M saline, 0.1 M lactic acid solutions and examined by scanning electron microscopy with EDX analysis. Immersion in 0.1M neutral saline was for 7 days. In the acidic solution, exposed interdendritic volumes in alloy N corroded completely away in 7 days with dissolution of Ni-enriched precipitate species as well as the copper-rich matrix. Alloy G begins to corrode more slowly but by a similar mechanism. The number density of an Fe-enriched species is insufficient to maintain a continuous galvanic potential to the copper matrix, and dissolution becomes imperceptible. In neutral saline solution, galvanic action alone caused pit-etching, without the dissolution of either precipitate species. The upper limit for the total dissolution of metallic ions in the standard immersion test can be set at 200 microg cm(-2). Aluminium bronze dental alloys can be expected to release both copper and nickel ions into an acidic oral environment.

Development and evaluation of new multiple-unit levodopa sustained-release floating dosage forms.

PubMed

Goole, J; Vanderbist, F; Amighi, K

2007-04-04

This work relates to the development and the in vitro evaluation of sustained-release minitablets (MT), prepared by melt granulation and subsequent compression, which are designed to float over an extended period of time. Levodopa was used as a model drug. The importance of the composition and manufacturing parameters of the MT on their floating and dissolution properties was then examined. The investigation showed that MT composition and MT diameter had the greatest influence on drug release, which was sustained for more than 8h. By using the same formulation, the best floating properties were obtained with 3mm MT prepared at low compression forces ranging between 50 and 100N. Their resultant-weight (RW) values were always higher than those obtained with a marketed HBS dosage form within 13h. When they were filled into gelatin capsules, no sticking was observed. By evaluating the dissolution profiles of levodopa at different pH values, it was found that dissolution profiles depend more on the prolonged-release ability of Methocel K15M than on the pH-dependent solubility of levodopa. Finally, the robustness of the floating MT was assessed by testing the drug release variability in function of the stirring conditions during dissolution tests.

Electrostatic Levitation Technique for Investigations of Physical Properties of Liquid States

NASA Astrophysics Data System (ADS)

Okada, Junpei; Ishikawa, Takehiko; Paradis, Paul-Francois; Yoda, Shinichi

Electrostatic levitator (ESL) levitates a charged sample in a high vacuum using computer con-trolled electrostatic fields [1]. It can levitate materials such as metals, semiconductors, and some insulators. Sample temperature can be varied over a wide range, and samples can be deeply undercooled. We have been engaged in the research and development of the electro-static levitation technique with the aim of performing levitation dissolution experiments in the International Space Station (ISS). Our device for the electrostatic levitation dissolution test has been developed for experiments on the ISS. To this end, the system is designed to be compact and portable so that it can be launched by rocket and used for experiments in the limited space on the ISS. Accordingly, the device can be installed not just on the ISS or our research laboratory, but also in various external sites. We devised a plan to install the electrostatic levitation system in a site other than the ISS to study atomic structure and electron structure of ultra-high-temperature liquids. We mounted our system on third generation synchrotron radiation facility "SPring-8" in Japan, to investigate the atomic and electron structures of high-temperature liquids. The SPring-8 is an experimental facility that allows use of the most powerful X-rays in the world. We conducted a variety of experiments on ultra-high-temperature liquids using SPring-8. The X-ray is ideal for exploring atomic structure and electron structure. Since the X-ray is an electromagnetic wave, it interacts with electrons. In addition, most electrons gather around the atomic nucleus. By close analysis of the scattered x-rays, we can determine its atomic structure and electron structure in detail. In this talk, we introduce an x-ray Compton scattering and x-ray Raman scattering measurements on liquid aluminum and silicon. [1] W. -K. Rhim, et al, Rev. Sci. Instrum. (1985) 56 307.

A microcomputer-based testing station for dynamic and static testing of protective relay systems

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

Lee, W.J.; Li, R.J.; Gu, J.C.

1995-12-31

Dynamic and static relay performance testing before installation in the field is a subject of great interest to utility relay engineers. The common practice in utility testing of new relays is to put the new unit to be tested in parallel with an existing functioning relay in the system, wait until an actual transient occurs and then observe and analyze the performance of new relay. It is impossible to have a thorough test of the protective relay system through this procedure. An equipment, Microcomputer-Based Testing Station (or PC-Based Testing Station), that can perform both static and dynamic testing of themore » relay is described in this paper. The Power System Simulation Laboratory at the University of Texas at Arlington is a scaled-down, three-phase, physical power system which correlates well with the important components for a real power system and is an ideal facility for the dynamic and static testing of protective relay systems. A brief introduction to the configuration of this laboratory is presented. Test results of several protective functions by using this laboratory illustrate the usefulness of this test set-up.« less

Static tensile and tensile creep testing of four boron nitride coated ceramic fibers at elevated temperatures

NASA Technical Reports Server (NTRS)

Coguill, Scott L.; Adams, Donald F.; Zimmerman, Richard S.

1989-01-01

Six types of uncoated ceramic fibers were static tensile and tensile creep tested at various elevated temperatures. Three types of boron nitride coated fibers were also tested. Room temperature static tensile tests were initially performed on all fibers, at gage lengths of 1, 2, and 4 inches, to determine the magnitude of end effects from the gripping system used. Tests at one elevated temperature, at gage lengths of 8 and 10 inches, were also conducted, to determine end effects at elevated temperatures. Fiber cross sectional shapes and areas were determined using scanning electron microscopy. Creep testing was typically performed for 4 hours, in an air atmosphere.

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

PubMed

Epstein, S; Cryer, B; Ragi, S; Zanchetta, J R; Walliser, J; Chow, J; Johnson, M A; Leyes, A E

2003-01-01

Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Biopharmaceutical classification of drugs using intrinsic dissolution rate (IDR) and rat intestinal permeability.

PubMed

Zakeri-Milani, Parvin; Barzegar-Jalali, Mohammad; Azimi, Mandana; Valizadeh, Hadi

2009-09-01

The solubility and dissolution rate of active ingredients are of major importance in preformulation studies of pharmaceutical dosage forms. In the present study, passively absorbed drugs are classified based on their intrinsic dissolution rate (IDR) and their intestinal permeabilities. IDR was determined by measuring the dissolution of a non-disintegrating disk of drug, and effective intestinal permeability of tested drugs in rat jejunum was determined using single perfusion technique. The obtained intrinsic dissolution rate values were in the range of 0.035-56.8 mg/min/cm(2) for tested drugs. The minimum and maximum intestinal permeabilities in rat intestine were determined to be 1.6 x 10(-5) and 2 x 10(-4)cm/s, respectively. Four classes of drugs were defined: Category I: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR>1(mg/min/cm(2)), Category II: P(eff,rat)>5 x 10(-5) (cm/s) or P(eff,human)>4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)), Category III: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR>1 (mg/min/cm(2)) and Category IV: P(eff,rat)<5 x 10(-5) (cm/s) or P(eff,human)<4.7 x 10(-5) (cm/s), IDR<1(mg/min/cm(2)). According to the results obtained and proposed classification of drugs, it is concluded that drugs could be categorized correctly based on their IDR and intestinal permeability values.

Structural testing for static failure, flutter and other scary things

NASA Technical Reports Server (NTRS)

Ricketts, R. H.

1983-01-01

Ground test and flight test methods are described that may be used to highlight potential structural problems that occur on aircraft. Primary interest is focused on light-weight general aviation airplanes. The structural problems described include static strength failure, aileron reversal, static divergence, and flutter. An example of each of the problems is discussed to illustrate how the data acquired during the tests may be used to predict the occurrence of the structural problem. While some rules of thumb for the prediction of structural problems are given the report is not intended to be used explicitly as a structural analysis handbook.

Pilot-scale tests of HEME and HEPA dissolution process

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

Qureshi, Z.H.; Strege, D.K.

A series of pilot-scale demonstration tests for the dissolution of High Efficiency Mist Eliminators (HEME`s) and High Efficiency Particulate Airfilters (HEPA) were performed on a 1/5th linear scale. These fiberglass filters are to be used in the Defense Waste Processing Facility (DWPF) to decontaminate the effluents from the off-gases generated during the feed preparation process and vitrification. When removed, these filters will be dissolved in the Decontamination Waste Treatment Tank (DWTT) using 5 wt% NaOH solution. The contaminated fiberglass is converted to an aqueous stream which will be transferred to the waste tanks. The filter metal structure will be rinsedmore » with process water before its disposal as low-level solid waste. The pilot-scale study reported here successfully demonstrated a simple one step process using 5 wt% NaOH solution. The proposed process requires the installation of a new water spray ring with 30 nozzles. In addition to the reduced waste generated, the total process time is reduced to 48 hours only (66% saving in time). The pilot-scale tests clearly demonstrated that the dissolution process of HEMEs has two stages - chemical digestion of the filter and mechanical erosion of the digested filter. The digestion is achieved by a boiling 5 wt% caustic solutions, whereas the mechanical break down of the digested filter is successfully achieved by spraying process water on the digested filter. An alternate method of breaking down the digested filter by increased air sparging of the solution was found to be marginally successful are best. The pilot-scale tests also demonstrated that the products of dissolution are easily pumpable by a centrifugal pump.« less

Wind Tunnel Testing of Various Disk-Gap-Band Parachutes

NASA Technical Reports Server (NTRS)

Cruz, Juan R.; Mineck, Raymond E.; Keller, Donald F.; Bobskill, Maria V.

2003-01-01

Two Disk-Gap-Band model parachute designs were tested in the NASA Langley Transonic Dynamics Tunnel. The purposes of these tests were to determine the drag and static stability coefficients of these two model parachutes at various subsonic Mach numbers in support of the Mars Exploration Rover mission. The two model parachute designs were designated 1.6 Viking and MPF. These model parachute designs were chosen to investigate the tradeoff between drag and static stability. Each of the parachute designs was tested with models fabricated from MIL-C-7020 Type III or F-111 fabric. The reason for testing model parachutes fabricated with different fabrics was to evaluate the effect of fabric permeability on the drag and static stability coefficients. Several improvements over the Viking-era wind tunnel tests were implemented in the testing procedures and data analyses. Among these improvements were corrections for test fixture drag interference and blockage effects, and use of an improved test fixture for measuring static stability coefficients. The 1.6 Viking model parachutes had drag coefficients from 0.440 to 0.539, while the MPF model parachutes had drag coefficients from 0.363 to 0.428. The 1.6 Viking model parachutes had drag coefficients 18 to 22 percent higher than the MPF model parachute for equivalent fabric materials and test conditions. Model parachutes of the same design tested at the same conditions had drag coefficients approximately 11 to 15 percent higher when manufactured from F-111 fabric as compared to those fabricated from MIL-C-7020 Type III fabric. The lower fabric permeability of the F-111 fabric was the source of this difference. The MPF model parachutes had smaller absolute statically stable trim angles of attack as compared to the 1.6 Viking model parachutes for equivalent fabric materials and test conditions. This was attributed to the MPF model parachutes larger band height to nominal diameter ratio. For both designs, model parachutes fabricated from F-111 fabric had significantly greater statically stable absolute trim angles of attack at equivalent test conditions as compared to those fabricated from MILC-7020 Type III fabric. This reduction in static stability exhibited by model parachutes fabricated from F-111 fabric was attributed to the lower permeability of the F-111 fabric. The drag and static stability coefficient results were interpolated to obtain their values at Mars flight conditions using total porosity as the interpolating parameter.

30 CFR 7.307 - Static pressure test.

Code of Federal Regulations, 2013 CFR

2013-07-01

... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.307 Static...) Permanent deformation exceeding 0.040 inches per linear foot; or (iii) Clearances, in excess of those...

30 CFR 7.307 - Static pressure test.

Code of Federal Regulations, 2014 CFR

2014-07-01

... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.307 Static...) Permanent deformation exceeding 0.040 inches per linear foot; or (iii) Clearances, in excess of those...

30 CFR 7.307 - Static pressure test.

Code of Federal Regulations, 2012 CFR

2012-07-01

... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.307 Static...) Permanent deformation exceeding 0.040 inches per linear foot; or (iii) Clearances, in excess of those...

30 CFR 7.307 - Static pressure test.

Code of Federal Regulations, 2011 CFR

2011-07-01

... APPROVAL OF MINING PRODUCTS TESTING BY APPLICANT OR THIRD PARTY Electric Motor Assemblies § 7.307 Static...) Permanent deformation exceeding 0.040 inches per linear foot; or (iii) Clearances, in excess of those...

Embedded data collector (EDC) phase II load and resistance factor design (LRFD).

DOT National Transportation Integrated Search

2015-09-01

A total of 16 static load test results was collected in Florida and Louisiana. New static load tests on five test piles : in Florida (four of which were voided) were monitored with Embedded Data Collector (EDC) instrumentation and : contributed to th...

Demonstration of Combined Zero-Valent Iron and Electrical Resistance Heating for In Situ Trichloroethene Remediation

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

Truex, Michael J.; Macbeth, Tamzen; Vermeul, Vincent R.

The effectiveness of in situ treatment using zero-valent iron to remediate sites with non-aqueous phase or significant sediment-associated contaminant mass can be limited by relatively low rates of mass transfer to bring contaminants in contact with the reactive media. For a field test in a trichloroethene source area, combining moderate-temperature (maximum 50oC) subsurface electrical resistance heating with in situ ZVI treatment was shown to accelerate dechlorination and dissolution rates by a factor of 4 to 6 based on organic daughter products and a factor 8-16 using a chloride concentrations. A mass-discharge-based analysis was used to evaluate reaction, dissolution, and volatilizationmore » at ambient groundwater temperature (~10oC) and as temperature was increased up to about 50oC. Increased reaction and contaminant dissolution were observed with increased temperature, but volatilization was minimal during the test because in situ reactions maintained low aqueous-phase TCE concentrations.« less

Implications of the stability behavior of zinc oxide nanoparticles for toxicological studies

NASA Astrophysics Data System (ADS)

Meißner, Tobias; Oelschlägel, Kathrin; Potthoff, Annegret

2014-08-01

The increasing use of zinc oxide (ZnO) nanoparticles in sunscreens and other cosmetic products demands a risk assessment that has to be done in toxicological studies. Such investigations require profound knowledge of the behavior of ZnO in cell culture media. The current study was performed to get well-dispersed suspensions of a hydrophilic (ZnO-hydro) and a lipophilic coated (ZnO-lipo) ZnO nanomaterial for use in in vitro tests. Therefore, systematic tests were carried out with common dispersants (phosphate, lecithin, proteins) to elucidate chemical and physical changes of ZnO nanoparticles in water and physiological solutions (PBS, DMEM). Non-physiological stock suspensions were prepared using ultrasonication. Time-dependent changes of pH, conductivity, zeta potential, particle size and dissolution were recorded. Secondly, the stock suspensions were added to physiological media with or without albumin (BSA) or serum (FBS), to examine characteristics such as agglomeration and dissolution. Stable stock suspensions were obtained using phosphate as natural and physiological electrostatic stabilizing agent. Lecithin proved to be an effective wetting agent for ZnO-lipo. Although the particle size remained constant, the suspension changed over time. The pH increased as a result of ZnO dissolution and formation of zinc phosphate complexes. The behavior of ZnO in physiological media was found to depend strongly on the additives used. Applying only phosphate as additive, ZnO-hydro agglomerated within minutes. In the presence of lecithin or BSA/serum, agglomeration was inhibited. ZnO dissolution was higher under physiological conditions than in the stock suspension. Serum especially promoted this process. Using body-related dispersants (phosphate, lecithin) non-agglomerating stock suspensions of hydrophilic and lipophilic ZnO were prepared as a prerequisite to perform meaningful toxicological investigation. Both nanomaterials showed a non-negligible dissolution behavior that strongly depended on the surrounding conditions. Agglomeration of ZnO particles in physiological media is a complex function of particle coating, used dispersants and serum proteins if supplemented. The present study gives a clear guideline how to prepare and handle suspensions with ZnO for in vitro testing and allows the correlation between the chemical-physical particles behavior with findings from toxicological tests.

Theoretical research and experimental validation of quasi-static load spectra on bogie frame structures of high-speed trains

NASA Astrophysics Data System (ADS)

Zhu, Ning; Sun, Shou-Guang; Li, Qiang; Zou, Hua

2014-12-01

One of the major problems in structural fatigue life analysis is establishing structural load spectra under actual operating conditions. This study conducts theoretical research and experimental validation of quasi-static load spectra on bogie frame structures of high-speed trains. The quasistatic load series that corresponds to quasi-static deformation modes are identified according to the structural form and bearing conditions of high-speed train bogie frames. Moreover, a force-measuring frame is designed and manufactured based on the quasi-static load series. The load decoupling model of the quasi-static load series is then established via calibration tests. Quasi-static load-time histories, together with online tests and decoupling analysis, are obtained for the intermediate range of the Beijing—Shanghai dedicated passenger line. The damage consistency calibration of the quasi-static discrete load spectra is performed according to a damage consistency criterion and a genetic algorithm. The calibrated damage that corresponds with the quasi-static discrete load spectra satisfies the safety requirements of bogie frames.

Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

PubMed

Sun, Dajun D; Lee, Ping I

2015-08-10

The objective of the current study is to mechanistically differentiate the dissolution and supersaturation behaviors of amorphous drugs from amorphous solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink dissolution conditions through a direct head-to-head comparison. ASDs of indomethacin (IND) were prepared in several polymers which exhibit different solubility behaviors in acidic (pH1.2) and basic (pH7.4) dissolution media. The selected polymers range from water-soluble (e.g., PVP and Soluplus) and water-insoluble (e.g., ethylcellulose and Eudragit RL PO) to those only soluble in an acidic or basic dissolution medium (e.g., Eudragit E100, Eudragit L100, and HPMCAS). At 20wt.% drug loading, DSC and powder XRD analysis confirmed that the majority of incorporated IND was present in an amorphous state. Our nonsink dissolution results confirm that whether the carrier matrix is medium soluble determines the release mechanism of amorphous drugs from ASD systems which has a direct impact on the rate of supersaturation generation, thus in turn affecting the evolution of supersaturation in amorphous systems. For example, under nonsink dissolution conditions, the release of amorphous IND from medium-soluble carriers is governed by a dissolution-controlled mechanism leading to an initial surge of supersaturation followed by a sharp decline in drug concentration due to rapid nucleation and crystallization. In contrast, the dissolution of IND ASD from medium-insoluble carriers is more gradual as drug release is regulated by a diffusion-controlled mechanism by which drug supersaturation is built up gradually and sustained over an extended period of time without any apparent decline. Since several tested carrier polymers can be switched from soluble to insoluble by simply changing the pH of the dissolution medium, the results obtained here provide unequivocal evidence of the proposed transition of kinetic solubility profiles from the same ASD system induced by changes in the drug release mechanism in dissolution medium of a different pH. Copyright © 2015 Elsevier B.V. All rights reserved.

A dynamic system for the simulation of fasting luminal pH-gradients using hydrogen carbonate buffers for dissolution testing of ionisable compounds.

PubMed

Garbacz, Grzegorz; Kołodziej, Bartosz; Koziolek, Mirko; Weitschies, Werner; Klein, Sandra

2014-01-23

The hydrogen carbonate buffer is considered as the most biorelevant buffer system for the simulation of intestinal conditions and covers the physiological pH range of the luminal fluids from pH 5.5 to about pH 8.4. The pH value of a hydrogen carbonate buffer is the result of a complex and dynamic interplay of the concentration of hydrogen carbonate ions, carbonic acid, the concentration of dissolved and solvated carbon dioxide and its partial pressure above the solution. The complex equilibrium between the different ions results in a thermodynamic instability of hydrogen carbonate solutions. In order to use hydrogen carbonate buffers with pH gradients in the physiological range and with the dynamics observed in vivo without changing the ionic strength of the solution, we developed a device (pHysio-grad®) that provides both acidification of the dissolution medium by microcomputer controlled carbon dioxide influx and alkalisation by degassing. This enables a continuous pH control and adjustment during dissolution of ionisable compounds. The results of the pH adjustment indicate that the system can compensate even rapid pH changes after addition of a basic or acidic moiety in amounts corresponding up to 90% of the overall buffer capacity. The results of the dissolution tests performed for a model formulation containing ionizable compounds (Nexium 20mg mups) indicate that both the simulated fasting intraluminal pH-profiles and the buffer species can significantly affect the dissolution process by changing the lag time prior to initial drug release and the release rate of the model compound. A prediction of the in vivo release behaviour of this formulation is thus most likely strongly related to the test conditions such as pH and buffer species. Copyright © 2013 Elsevier B.V. All rights reserved.

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability.

PubMed

Dennison, Thomas J; Smith, Julian C; Badhan, Raj K; Mohammed, Afzal R

2017-01-01

Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (P app ) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f 1 ) and similarity (f 2 ) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating P app and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in C max and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated bioequivalence of an FDC ODT for amlodipine and atorvastatin, while highlighting several limitations of f 1 and f 2 bioequivalence testing and strengths of mechanistic pharmacokinetic modeling for oral drug absorption.

Fixed-dose combination orally disintegrating tablets to treat cardiovascular disease: formulation, in vitro characterization and physiologically based pharmacokinetic modeling to assess bioavailability

PubMed Central

Dennison, Thomas J; Smith, Julian C; Badhan, Raj K; Mohammed, Afzal R

2017-01-01

Cardiovascular disease (CVD) is the leading cause of death among men and women worldwide. In CVD, hypertension and dyslipidemia commonly coexist and are managed through coadministration of amlodipine and atorvastatin, respectively. The case for fixed-dose combination (FDC) oral dosage forms and orally disintegrating tablet (ODT) technology to enhance outcomes and compliance is strong. This work follows the development and characterization of single and FDC ODTs containing amlodipine and atorvastatin, followed by bioequivalence comparison between these single and FDC formulations, using in vitro dissolution and Caco-2 apparent permeability (Papp) and in silico physiologically based pharmacokinetic modeling approaches. ODTs containing amlodipine (5 mg) and atorvastatin (10 mg) either alone or in combination rapidly disintegrated (<30 s) while displaying a radial crushing strength in excess of 100 N and friability ≤1%. In vitro dissolution test was performed in fasted and fed-state simulated intestinal fluid (FeSSIF) and analyzed using high-performance liquid chromatography. Dissolution profiles for single and FDC ODTs were compared using US FDA recommended difference (f1) and similarity (f2) factor testing for bioequivalence. In all cases, there was no difference in active pharmaceutical ingredient dissolution between single or FDC ODTs, with the exception of amlodipine in FeSSIF. Pharmacokinetic clinical trial simulations were conducted using Simcyp (Version 14), incorporating Papp and dissolution data. Simulated clinical trials in healthy volunteers showed no difference in bioavailability based on pharmacokinetic parameters between single and combination doses with either active pharmaceutical ingredient. An increase in Cmax and AUC for atorvastatin in fed subjects was attributed to extended transit along the gut lumen and reduced atorvastatin metabolism due to lower CYP3A4 expression at more distal small intestine absorption sites. The results demonstrated bioequivalence of an FDC ODT for amlodipine and atorvastatin, while highlighting several limitations of f1 and f2 bioequivalence testing and strengths of mechanistic pharmacokinetic modeling for oral drug absorption. PMID:28352156

Dissolution testing of isoniazid, rifampicin, pyrazinamide and ethambutol tablets using near-infrared spectroscopy (NIRS) and multivariate calibration.

PubMed

de Oliveira Neves, Ana Carolina; Soares, Gustavo Mesquita; de Morais, Stéphanie Cavalcante; da Costa, Fernanda Saadna Lopes; Porto, Dayanne Lopes; de Lima, Kássio Michell Gomes

2012-01-05

This work utilized the near-infrared spectroscopy (NIRS) and multivariate calibration to measure the percentage drug dissolution of four active pharmaceutical ingredients (APIs) (isoniazid, rifampicin, pyrazinamide and ethambutol) in finished pharmaceutical products produced in the Federal University of Rio Grande do Norte (Brazil). The conventional analytical method employed in quality control tests of the dissolution by the pharmaceutical industry is high-performance liquid chromatography (HPLC). The NIRS is a reliable method that offers important advantages for the large-scale production of tablets and for non-destructive analysis. NIR spectra of 38 samples (in triplicate) were measured using a Bomen FT-NIR 160 MB in the range 1100-2500nm. Each spectrum was the average of 50 scans obtained in the diffuse reflectance mode. The dissolution test, which was initially carried out in 900mL of 0.1N hydrochloric acid at 37±0.5°C, was used to determine the percentage a drug that dissolved from each tablet measured at the same time interval (45min) at pH 6.8. The measurement of the four API was performed by HPLC (Shimadzu, Japan) in the gradiente mode. The influence of various spectral pretreatments (Savitzky-Golay smoothing, Multiplicative Scatter Correction (MSC), and Savitzky-Golay derivatives) and multivariate analysis using the partial least squares (PLS) regression algorithm was calculated by the Unscrambler 9.8 (Camo) software. The correlation coefficient (R(2)) for the HPLC determination versus predicted values (NIRS) ranged from 0.88 to 0.98. The root-mean-square error of prediction (RMSEP) obtained from PLS models were 9.99%, 8.63%, 8.57% and 9.97% for isoniazid, rifampicin, ethambutol and pyrazinamide, respectively, indicating that the NIR method is an effective and non-destructive tool for measurement of drug dissolution from tablets. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Solubility and bioavailability improvement of pazopanib hydrochloride.

PubMed

Herbrink, Maikel; Groenland, Stefanie L; Huitema, Alwin D R; Schellens, Jan H M; Beijnen, Jos H; Steeghs, Neeltje; Nuijen, Bastiaan

2018-06-10

The anti-cancer drug pazopanib hydrochloride (PZH) has a very low aqueous solubility and a variable oral bioavailability. A new pharmaceutical formulation with an improved solubility may enhance the bioavailability and reduce the variability. A broad selection of polymer excipients was tested for their compatibility and solubilizing properties by conventional microscopic, thermal and spectrometric techniques. A wet milling and mixing technique was used to produce homogenous powder mixtures. The dissolution properties of the formulation were tested by a pH-switch dissolution model. The final formulation was tested in vivo in cancer patient following a dose escalation design. Of the tested mixture formulations, the one containing the co-block polymer Soluplus® in a 8:1 ratio with PZH performed best in terms of in vitro dissolution properties. The in vivo results indicated that 300 mg of the developed formulation yields similar exposure and a lower variability (379 μg/mL∗h (36.7% CV)) than previously reported values for the standard PZH formulation (Votrient®) at the approved dose of 800 mg. Furthermore, the expected plasma-C through levels (27.2 μg/mL) exceeds the defined therapeutic efficacy threshold of 20 μg/mL. Copyright © 2018 Elsevier B.V. All rights reserved.

Stable amorphous binary systems of glipizide and atorvastatin powders with enhanced dissolution profiles: formulation and characterization.

PubMed

Renuka; Singh, Sachin Kumar; Gulati, Monica; Narang, Rakesh

2017-02-01

The aim of this study was to enhance the dissolution profile of the combination of glipizide and atorvastatin used for simultaneous treatment of hyperglycemia and hyperlipidemia. The strategy to formulate coamorphous glipizide-atorvastatin binary mixture was explored to achieve enhancement in dissolution. The coamorphous glipizide-atorvastatin mixtures (1:1, 1:2 and 2:1) were prepared by cryomilling and characterized with respect to their dissolution profiles, preformulation parameters and physical stability. Amorphization was found to be possible by cryomilling at various tried ratios of the two drugs. The data obtained from glass transition temperatures and from Raman spectroscopy point toward practically no interaction between the two drugs. The dissolution studies revealed the highest enhancement in dissolution profiles of cryomilled coamorphous mixtures containing GPZ:ATV in ratios 1:1 (B-5) and 2:1 (B-7). These two mixtures were, therefore, subjected to studies for the evaluation of precompression parameters in order to find their amenability to satisfactory compression into tablet dosage form. The selected formulation was found to be stable when subjected to accelerated stability testing at 40°. C/75% RH for six months as per ICH guidelines. Based on all these studies, it was concluded that GPZ:ATV (1:1) combination may be able to provide an effective therapy for the comorbidities of hyperglycemia and hyperlipidemia.

Computational fluid dynamics (CFD) studies of a miniaturized dissolution system.

PubMed

Frenning, G; Ahnfelt, E; Sjögren, E; Lennernäs, H

2017-04-15

Dissolution testing is an important tool that has applications ranging from fundamental studies of drug-release mechanisms to quality control of the final product. The rate of release of the drug from the delivery system is known to be affected by hydrodynamics. In this study we used computational fluid dynamics to simulate and investigate the hydrodynamics in a novel miniaturized dissolution method for parenteral formulations. The dissolution method is based on a rotating disc system and uses a rotating sample reservoir which is separated from the remaining dissolution medium by a nylon screen. Sample reservoirs of two sizes were investigated (SR6 and SR8) and the hydrodynamic studies were performed at rotation rates of 100, 200 and 400rpm. The overall fluid flow was similar for all investigated cases, with a lateral upward spiraling motion and central downward motion in the form of a vortex to and through the screen. The simulations indicated that the exchange of dissolution medium between the sample reservoir and the remaining release medium was rapid for typical screens, for which almost complete mixing would be expected to occur within less than one minute at 400rpm. The local hydrodynamic conditions in the sample reservoirs depended on their size; SR8 appeared to be relatively more affected than SR6 by the resistance to liquid flow resulting from the screen. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect drug loading process on dissolution mechanism of encapsulated amoxicillin trihydrate in hydrogel semi-IPN chitosan methyl cellulose with pore forming agent KHCO3 as a floating drug delivery system

NASA Astrophysics Data System (ADS)

Fithawati, Garnis; Budianto, Emil

2018-04-01

Common treatment for Helicobacter pylori by repeated oral consumption of amoxicillin trihydrate is not effective. Amoxicillin trihydrate has a very short residence time in stomach which leads into its ineffectiveness. Residence time of amoxicillin trihydrate can be improved by encapsulating amoxicillin trihydrate into a floating drug delivery system. In this study, amoxicillin trihydrate is encapsulated into hydrogel semi-IPN chitosan methyl cellulose matrix as a floating drug delivery system and then treated with 20% KHCO3 as pore forming agent. Drug loading process used are in-situ loading and post loading. In-situ loading process has higher efficiency percentage and dissolution percentage than post loading process. In-situ loading process resulted 100% efficiency with 92,70% dissolution percentage. Post loading process resulted 98,7% efficiency with 90,42% dissolution percentage. Mechanism of drug dissolution study by kinetics approach showed both in-situ loading process and post loading process are diffusion and degradation process (n=0,4913) and (n=0,4602) respectively. These results are supported by characterization data from optical microscope and scanning electron microscopy (SEM). Data from optical microscope showed both loading process resulted in coarser hydrogel surface. Characterization using SEM showed elongated pores in both loading process after dissolution test.

EFFECT OF MAGNESIUM STEARATE CONCENTRATION ON DISSOLUTION PROPERTIES OF RANITIDINE HYDROCHLORIDE COATED TABLETS

PubMed Central

Uzunović, Alija; Vranić, Edina

2007-01-01

Most pharmaceutical formulations also include a certain amount of lubricant to improve their flowability and prevent their adhesion to the surfaces of processing equipment. Magnesium stearate is an additive that is most frequently used as a lubricant. Magnesium stearate is capable of forming films on other tablet excipients during prolonged mixing, leading to a prolonged drug liberation time, a decrease in hardness, and an increase in disintegration time. It is hydrophobic, and there are many reports in the literature concerning its adverse effect on dissolution rates. The objective of this study was to evaluate the effects of two different concentrations of magnesium stearate on dissolution properties of ranitidine hydrochloride coated tablet formulations labeled to contain 150 mg. The uniformity content was also checked. During the drug formulation development, several samples were designed for choice of the formulation. For this study, two formulations containing 0,77 and 1,1% of magnesium stearate added in the manufacture of cores were chosen. Fraction of ranitidine hydrochloride released in dissolution medium was calculated from calibration curves. The data were analyzed using pharmaco-peial test for similarity of dissolution profiles (f2 equation), previously proposed by Moore and Flanner. Application of f2 equation showed differences in time-course of ranitidine hydrochloride dissolution properties. The obtained values indicate differences in drug release from analyzed ranitidine hydrochloride formulations and could cause differences in therapeutic response. PMID:17848158

Improving the dissolution rate of poorly water soluble drug by solid dispersion and solid solution: pros and cons.

PubMed

Chokshi, Rina J; Zia, Hossein; Sandhu, Harpreet K; Shah, Navnit H; Malick, Waseem A

2007-01-01

The solid dispersions with poloxamer 188 (P188) and solid solutions with polyvinylpyrrolidone K30 (PVPK30) were evaluated and compared in an effort to improve aqueous solubility and bioavailability of a model hydrophobic drug. All preparations were characterized by differential scanning calorimetry, powder X-ray diffraction, intrinsic dissolution rates, and contact angle measurements. Accelerated stability studies also were conducted to determine the effects of aging on the stability of various formulations. The selected solid dispersion and solid solution formulations were further evaluated in beagle dogs for in vivo testing. Solid dispersions were characterized to show that the drug retains its crystallinity and forms a two-phase system. Solid solutions were characterized to be an amorphous monophasic system with transition of crystalline drug to amorphous state. The evaluation of the intrinsic dissolution rates of various preparations indicated that the solid solutions have higher initial dissolution rates compared with solid dispersions. However, after storage at accelerated conditions, the dissolution rates of solid solutions were lower due to partial reversion to crystalline form. The drug in solid dispersion showed better bioavailability in comparison to solid solution. Therefore, considering physical stability and in vivo study results, the solid dispersion was the most suitable choice to improve dissolution rates and hence the bioavailability of the poorly water soluble drug.

Pharmaceutical Equivalence of Clarithromycin Oral Dosage Forms Marketed in Nairobi County, Kenya

PubMed Central

Manani, Rebecca O.; Abuga, Kennedy O.; Chepkwony, Hezekiah K.

2017-01-01

Clarithromycin is a broad-spectrum semi-synthetic macrolide indicated for treatment of pneumonias, Helicobacter pylori, and chlamydial and skin infections. The object of this study was to evaluate the pharmaceutical equivalence of 14 generic clarithromycin products marketed in Nairobi County, Kenya, to the innovator products, using in vitro dissolution profiles and similarity factors (f2). Further, dissolution profiles of four innovator formulations manufactured in different sites were compared. Fourteen clarithromycin tablets/capsules and four suspensions were subjected to assay and comparative dissolution runs at pH 1.2, 4.5 and 6.8, for 60 and 90 min, respectively. All products complied with pharmacopoeial assay specifications. However, significant differences were observed in their dissolution profiles. The non-compliance rates for tablets/capsules were 50% at pH 1.2, 33% at pH 4.5 and 50% at pH 6.8, while none of the four suspensions were compliant. Overall, only four (25%) products complied with the specifications for similarity factor. The results obtained indicate that a significant percentage of generic clarithromycin products are pharmaceutically non-equivalent to the innovator products, and that assay and single-point dissolution tests are insufficient demonstration of equivalence between the generic and innovator products. PMID:28445444

HIV status awareness, partnership dissolution and HIV transmission in generalized epidemics.

PubMed

Reniers, Georges; Armbruster, Benjamin

2012-01-01

HIV status aware couples with at least one HIV positive partner are characterized by high separation and divorce rates. This phenomenon is often described as a corollary of couples HIV Testing and Counseling (HTC) that ought to be minimized. In this contribution, we demonstrate the implications of partnership dissolution in serodiscordant couples for the propagation of HIV. We develop a compartmental model to study epidemic outcomes of elevated partnership dissolution rates in serodiscordant couples and parameterize it with estimates from population-based data (Rakai, Uganda). Via its effect on partnership dissolution, every percentage point increase in HIV status awareness reduces HIV incidence in monogamous populations by 0.27 percent for women and 0.63 percent for men. These effects are even larger when the assumption of monogamy can be relaxed, but are moderated by other behavior changes (e.g., increased condom use) in HIV status aware serodiscordant partnerships. When these behavior changes are taken into account, each percentage point increase in HIV status awareness reduces HIV incidence by 0.13 and 0.32 percent for women and men, respectively (assuming monogamy). The partnership dissolution effect exists because it decreases the fraction of serodiscordant couples in the population and prolongs the time that individuals spend outside partnerships. Our model predicts that elevated partnership dissolution rates in HIV status aware serodiscordant couples reduce the spread of HIV. As a consequence, the full impact of couples HTC for HIV prevention is probably larger than recognized to date. Particularly high partnership dissolution rates in female positive serodiscordant couples contribute to the gender imbalance in HIV infections.

Short Durations of Static Stretching when Combined with Dynamic Stretching do not Impair Repeated Sprints and Agility

PubMed Central

Wong, Del P.; Chaouachi, Anis; Lau, Patrick W.C.; Behm, David G.

2011-01-01

This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA) and change of direction (COD). Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s). Three dynamic stretching exercises of 30 s duration were then performed (90 s total). Sit-and-reach flexibility tests were conducted before the aerobic warm up, after the combined static and dynamic stretching, and post- RSA/COD test. The duration of static stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit-and-reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). However there were no significant differences in RSA and COD performance between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. Furthermore, the short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. Key points The duration of combined static and dynamic stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit and reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). No significant differences in RSA and COD between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. The short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. PMID:24149890

Short Durations of Static Stretching when Combined with Dynamic Stretching do not Impair Repeated Sprints and Agility.

PubMed

Wong, Del P; Chaouachi, Anis; Lau, Patrick W C; Behm, David G

2011-01-01

This study aimed to compare the effect of different static stretching durations followed by dynamic stretching on repeated sprint ability (RSA) and change of direction (COD). Twenty-five participants performed the RSA and COD tests in a randomized order. After a 5 min aerobic warm up, participants performed one of the three static stretching protocols of 30 s, 60 s or 90 s total duration (3 stretches x 10 s, 20 s or 30 s). Three dynamic stretching exercises of 30 s duration were then performed (90 s total). Sit-and-reach flexibility tests were conducted before the aerobic warm up, after the combined static and dynamic stretching, and post- RSA/COD test. The duration of static stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit-and-reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001). However there were no significant differences in RSA and COD performance between the 3 stretching conditions. The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects. Furthermore, the short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments. Key pointsThe duration of combined static and dynamic stretching had a positive effect on flexibility with 36.3% and 85.6% greater sit and reach scores with the 60 s and 90 s static stretching conditions respectively than with the 30 s condition (p ≤ 0.001).No significant differences in RSA and COD between the 3 stretching conditions.The lack of change in RSA and COD might be attributed to a counterbalancing of static and dynamic stretching effects.The short duration (≤ 90 s) static stretching may not have provided sufficient stimulus to elicit performance impairments.

40. 500,000 POUND STATIC TEST FACILITY: DISTANT VIEW WITH BLOCKHOUSE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

40. 500,000 POUND STATIC TEST FACILITY: DISTANT VIEW WITH BLOCKHOUSE IN FOREGROUND, LOOKING SOUTHEAST - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

40 CFR Table F-2 to Subpart F of... - Particle Sizes and Wind Speeds for Full Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and...

Code of Federal Regulations, 2012 CFR

2012-07-01

... Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and Static Chamber Test F Table F-2 to Subpart F... Part 53—Particle Sizes and Wind Speeds for Full Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and Static Chamber Test Primary Partical Mean Size a (µm) Full Wind Tunnel Test 2 km/hr 24 km/hr Inlet...

40 CFR Table F-2 to Subpart F of... - Particle Sizes and Wind Speeds for Full Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and...

Code of Federal Regulations, 2013 CFR

2013-07-01

... Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and Static Chamber Test F Table F-2 to Subpart F... Part 53—Particle Sizes and Wind Speeds for Full Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and Static Chamber Test Primary Partical Mean Size a (µm) Full Wind Tunnel Test 2 km/hr 24 km/hr Inlet...

40 CFR Table F-2 to Subpart F of... - Particle Sizes and Wind Speeds for Full Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and...

Code of Federal Regulations, 2014 CFR

2014-07-01

... Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and Static Chamber Test F Table F-2 to Subpart F... Part 53—Particle Sizes and Wind Speeds for Full Wind Tunnel Test, Wind Tunnel Inlet Aspiration Test, and Static Chamber Test Primary Partical Mean Size a (µm) Full Wind Tunnel Test 2 km/hr 24 km/hr Inlet...

Rectifier cabinet static breaker

DOEpatents

Costantino, Jr, Roger A.; Gliebe, Ronald J.

1992-09-01

A rectifier cabinet static breaker replaces a blocking diode pair with an SCR and the installation of a power transistor in parallel with the latch contactor to commutate the SCR to the off state. The SCR serves as a static breaker with fast turnoff capability providing an alternative way of achieving reactor scram in addition to performing the function of the replaced blocking diodes. The control circuitry for the rectifier cabinet static breaker includes on-line test capability and an LED indicator light to denote successful test completion. Current limit circuitry provides high-speed protection in the event of overload.

Advanced manufacturing development of a composite empennage component for L-1011 aircraft. Phase 4: Full scale ground test

NASA Technical Reports Server (NTRS)

Jackson, A. C.; Dorwald, F.

1982-01-01

The ground tests conducted on the advanced composite vertical fin (ACVF) program are described. The design and fabrication of the test fixture and the transition structure, static test of Ground Test Article (GTA) No. 1, rework of GTA No. 2, and static, damage tolerance, fail-safe and residual strength tests of GTA No. 2 are described.

Testing of the Defense Waste Processing Facility Cold Chemical Dissolution Method in Sludge Batch 9 Qualification

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

Edwards, T.; Pareizs, J.; Coleman, C.

For each sludge batch that is processed in the Defense Waste Processing Facility (DWPF), the Savannah River National Laboratory (SRNL) tests the applicability of the digestion methods used by the DWPF Laboratory for elemental analysis of Sludge Receipt and Adjustment Tank (SRAT) Receipt samples and SRAT Product process control samples. DWPF SRAT samples are typically dissolved using a method referred to as the DWPF Cold Chemical or Cold Chem Method (CC), (see DWPF Procedure SW4- 15.201). Testing indicates that the CC method produced mixed results. The CC method did not result in complete dissolution of either the SRAT Receipt ormore » SRAT Product with some fine, dark solids remaining. However, elemental analyses did not reveal extreme biases for the major elements in the sludge when compared with analyses obtained following dissolution by hot aqua regia (AR) or sodium peroxide fusion (PF) methods. The CC elemental analyses agreed with the AR and PF methods well enough that it should be adequate for routine process control analyses in the DWPF after much more extensive side-by-side tests of the CC method and the PF method are performed on the first 10 SRAT cycles of the Sludge Batch 9 (SB9) campaign. The DWPF Laboratory should continue with their plans for further tests of the CC method during these 10 SRAT cycles.« less

Millennials in the Fire Service: The Effectiveness of Fire Service Recruiting, Testing, and Retention

DTIC Science & Technology

2017-12-01

to effectively attract and retain millennials is in question. Stale marketing and static testing processes may be contributing to smaller hiring pools...ABSTRACT Modern-day fire service methods’ ability to effectively attract and retain millennials is in question. Stale marketing and static testing... Marketing of the Testing Process ..............................................................50  Table 6.  Type of Testing Process

Nystatin and lidocaine pastilles for the local treatment of oral mucositis.

PubMed

Silva, Filipa Cosme; Marto, Joana M; Salgado, Ana; Machado, Paula; Silva, Alexandra N; Almeida, António J

2017-03-01

Oral mucositis (OM) is a common adverse reaction to radiotherapy and chemotherapy in oncology. Its treatment requires oral formulations that enhance therapy compliance, improve administration and ensure drug effectiveness. Solid dosage forms that act by slow dissolution, such as pastilles, are an effective alternative to mouthwashes, for their versatility, ease of administration and extended residence time in the oral cavity. The present work describes the development and stability studies of an innovative formulation of nystatin and lidocaine pastilles for the treatment of oral mucositis. Full pharmaceutical quality testing was carried out, including disintegration and dissolution testing, texture profile analysis, grittiness and an antifungal activity testing. A soft pastille formulation containing 0.25% lidocaine and 78,000 IU nystatin was obtained, presenting suitable pharmaceutical characteristics, as a disintegration time of 17 ± 2 min, dissolution rate and microbiological and physicochemical for 30 days when stored at 2-8 °C under light protection. Palatability was also evaluated, being well accepted by a panel of 38 healthy volunteers. This formulation allows an accurate drug dosing by the prescriber, while enabling the patients to control the retention time of the drugs in the oral cavity and consequently manage their pain treatment.

Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin.

PubMed

Chua, Hui Ming; Hauet Richer, Nathalie; Swedrowska, Magda; Ingham, Stephen; Tomlin, Stephen; Forbes, Ben

2016-01-07

Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.

Effects of Antiparasitic Treatment on Dynamically and Statically Tested Cognitive Skills over Time

ERIC Educational Resources Information Center

Grigorenko, Elena L.; Sternberg, Robert J.; Jukes, Mathew; Alcock, Katie; Lambo, Jane; Ngorosho, Damaris; Nokes, Catherine; Bundy, Donald A.

2006-01-01

The main objective of this work was to investigate two testing procedures, repeated static tests and dynamic testing, that can more clearly demonstrate the impact of treatment for parasites in children. Rural Tanzanian children were assessed for the presence/absence and burden of helminth parasites and assigned to one of three…

Characterization of Friction Joints Subjected to High Levels of Random Vibration

NASA Technical Reports Server (NTRS)

deSantos, Omar; MacNeal, Paul

2012-01-01

This paper describes the test program in detail including test sample description, test procedures, and vibration test results of multiple test samples. The material pairs used in the experiment were Aluminum-Aluminum, Aluminum- Dicronite coated Aluminum, and Aluminum-Plasmadize coated Aluminum. Levels of vibration for each set of twelve samples of each material pairing were gradually increased until all samples experienced substantial displacement. Data was collected on 1) acceleration in all three axes, 2) relative static displacement between vibration runs utilizing photogrammetry techniques, and 3) surface galling and contaminant generation. This data was used to estimate the values of static friction during random vibratory motion when "stick-slip" occurs and compare these to static friction coefficients measured before and after vibration testing.

Improvement of the stability of hydroxyapatite through glass ceramic reinforcement.

PubMed

Ha, Na Ra; Yang, Zheng Xun; Hwang, Kyu Hong; Kim, Tae Suk; Lee, Jong Kook

2010-05-01

Hydroxyapatite has achieved significant application in orthopedic and dental implants due to its excellent biocompatibility. Sintered hydroxyapatites showed significant dissolution, however, after their immersion in water or simulated body fluid (SBF). This grain boundary dissolution, even in pure hydroxyapatites, resulted in grain separation at the surfaces, and finally, in fracture. In this study, hydroxyapatite ceramics containing apatite-wollastonite (AW) or calcium silicate (SG) glass ceramics as additives were prepared to prevent the dissolution. AW and SG glass ceramics were added at 0-7 wt% and powder-compacted uniaxially followed by firing at moisture conditions. The glass phase was incorporated into the hydroxyapatite to act as a sintering aid, followed by crystallization, to improve the mechanical properties without reducing the biocompatibility. As seen in the results of the dissolution test, a significant amount of damage was reduced even after more than 14 days. TEM and SEM showed no decomposition of HA to the secondary phase, and the fracture toughness increased, becoming even higher than that of the commercial hydroxyapatite.

Real-time dissolution measurement of sized and unsized calcium phosphate glass fibers.

PubMed

Rinehart, J D; Taylor, T D; Tian, Y; Latour, R A

1999-01-01

The objective of this study was to develop an efficient "real time" measurement system able to directly measure, with microgram resolution, the dissolution rate of absorbable glass fibers, and utilize the system to evaluate the effectiveness of silane-based sizing as a means to delay the fiber dissolution process. The absorbable glass fiber used was calcium phosphate (CaP), with tetramethoxysilane selected as the sizing agent. E-glass fiber was used as a relatively nondegrading control. Both the unsized-CaP and sized-CaP degraded linearly at both the 37 degrees C and 60 degrees C test temperature levels used. No significant decrease in weight-loss rate was recorded when the CaP fiber tows were pretreated, using conventional application methods, with the tetramethoxysilane sizing for either temperature condition. The unsized-CaP and sized-CaP weight loss rates were each significantly higher at 60 than at 37 degrees C (both p < 0.02), as expected from dissolution kinetics. In terms of actual weight loss rate measured using our system for phosphate glass fiber, the unsized-CaP fiber we studied dissolved at a rate of 10.90 x 10(-09) and 41.20 x 10(-09) g/min-cm(2) at 37 degrees C and 60 degrees C, respectively. Considering performance validation of the developed system, the slope of the weight loss vs. time plot for the tested E-glass fiber was not significantly different compared to a slope equal to zero for both test temperatures. Copyright 1999 John Wiley & Sons, Inc.

Formulation and in-vitro evaluation of directly compressed controlled release matrices of Losartan Potassium using Ethocel Grade 100 as rate retarding agent.

PubMed

Khan, Kamran Ahmad; Khan, Gul Majid; Zeeshan Danish, Muhammad; Akhlaq; Khan, Haroon; Rehman, Fazal; Mehsud, Saifullah

2015-12-30

Current study was aimed to develop 200mg controlled release matrix tablets of Losartan Potassium using Ethocel 100 Premium and Ethocel 100 FP Premium as rate controlling polymer. In-vitro studies were performed according to USP Method-I in phosphate buffer (PH 6.8) using pharma test dissolution apparatus. The temperature of the dissolution medium was kept constant at 37±0.5°C at 100rpm. Flow properties, physical quality control tests, effect of polymer size and drug-to-polymers ratios were studied using different kinetics models such as 1st-order, zero-order, Hixon Crowell model, Highuchi model and Power law. Difference factor f1 and similarity factor f2 were applied for dissolution profiles against Cardaktin® tablets used as a reference formulation. The matrices with polymer ethocel 100 FP Premiums have prolonged the drug release rate as compared to polymer ethocel 100 Premiums. The n values matrices with polymer ethocel grade 100 ranged from 0.603 to 0.857 indicating that the drug release occurred by anomalous non fickian diffusion kinetics while then value of reference Cardaktin® tablet was measured as 0.125 indicating that these tablets do not follow power law. The dissolution profiles of test formulations were different than that of reference Cardaktin®. This suggests the polymer Ethocel grade 100 can be proficiently incorporated in fabrication and development of once a day controlled release matrix tablets. Copyright © 2015. Published by Elsevier B.V.

Radiochemical purity of Mo and Tc solution obtained after irradiation and dissolution of Mo-100-enriched and ultra-high-purity natural Mo disks

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

Tkac, Peter; Gromov, Roman; Chemerisov, Sergey D.

2016-09-01

Four irradiations of ultra-high-purity natural Mo targets and one irradiation using 97.4% Mo-100-enriched material were performed. The purpose of these irradiations was to determine whether the presence of Sn stabilizer in the H 2O 2 used for the dissolution of sintered Mo disks can affect the radiochemical purity of the final K 2MoO 4 in 5M KOH solution. Results from radiochemical purity tests performed using thin-layer paper chromatography show that even 2– 3× excess of Sn-stabilized H 2O 2 typically used for dissolution of sintered Mo disks did not affect the radiochemical purity of the final product.

K-Basin gel formation studies

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

Beck, M.A.

1998-07-23

A key part of the proposed waste treatment for K Basin sludge is the elimination of reactive uranium metal by dissolution in nitric acid (Fkirnent, 1998). It has been found (Delegard, 1998a) that upon nitric acid dissolution of the sludge, a gel sometimes forms. Gels are known to sometimes impair solid/liquid separation and/or material transfer. The purpose of the work reported here is to determine the cause(s) of the gel formation and to determine operating parameters for the sludge dissolution that avoid formation of gel. This work and related work were planned in (Fkunent, 1998), (Jewett, 1998) and (Beck, 1998a).more » This report describes the results of the tests in (Beck, 1998a) with non-radioactive surrogates.« less

Static strain and vibration characteristics of a metal semimonocoque helicopter tail cone of moderate size

NASA Technical Reports Server (NTRS)

Bielawa, Richard L.; Hefner, Rachel E.; Castagna, Andre

1991-01-01

The results are presented of an analytic and experimental research program involving a Sikorsky S-55 helicopter tail cone directed ultimately to the improved structural analysis of airframe substructures typical of moderate sized helicopters of metal semimonocoque construction. Experimental static strain and dynamic shake-testing measurements are presented. Correlation studies of each of these tests with a PC-based finite element analysis (COSMOS/M) are described. The tests included static loadings at the end of the tail cone supported in the cantilever configuration as well as vibrational shake-testing in both the cantilever and free-free configurations.

Saturn Apollo Program

NASA Image and Video Library

1967-09-09

This photograph depicts the F-1 engine firing in the Marshall Space Flight Center’s F-1 Engine Static Test Stand. Construction of the S-IC Static test stand complex began in 1961 in the west test area of MSFC, and was completed in 1964. It is a vertical engine firing test stand, 239 feet in elevation and 4,600 square feet in area at the base, designed to assist in the development of the F-1 Engine. Capability is provided for static firing of 1.5 million pounds of thrust using liquid oxygen and kerosene. The foundation of the stand is keyed into the bedrock approximately 40 feet below grade.

Instance Analysis for the Error of Three-pivot Pressure Transducer Static Balancing Method for Hydraulic Turbine Runner

NASA Astrophysics Data System (ADS)

Weng, Hanli; Li, Youping

2017-04-01

The working principle, process device and test procedure of runner static balancing test method by weighting with three-pivot pressure transducers are introduced in this paper. Based on an actual instance of a V hydraulic turbine runner, the error and sensitivity of the three-pivot pressure transducer static balancing method are analysed. Suggestions about improving the accuracy and the application of the method are also proposed.

New chemolysis for urological calcium phosphate calculi – a study in vitro

PubMed Central

Xiang-bo, Zhang; Zhi-ping, Wang; Jian-min, Duan; Jian-zhong, Lu; Bao-liang, Ma

2005-01-01

Background Advances in techniques have left very few indications for open surgical extraction of urinary stones currently. These advances notwithstanding, the search continues for medical approaches to urinary stone management. In this study, we perform an in vitro study analyzing the efficiency and prospect of two new complex solutions in urological calcium phosphate calculi dissolution. Methods Eighteen stones composed mainly of calcium phosphates were taken from patients who underwent kidney stone surgery. These stones were large enough (weight range 0.514–0.928 g) to be fragmented and matched equally into six groups. Chemolysis of phosphate stones was done with six different solvents and was repeated 3 times with 6 stones for each solution. At 24, 48 and 72 h, reduction in weight, percentage weight change, and dissolution rate; the dissolution rates at pH 5.0, 7.0 and 8.5 for each solution, using different cations (Na+, K+ or Ca2+), according to different dilutions (1:1, 1:2, 1:3, 1:4) of S1 and S2 were simultaneously determined. Results Calcium phosphate calculi were poorly dissolved by Phys and Art, and they had a low dissolution rate in pH 8.5 EDTA. The most effective solutions were S1, S2 and R, with 72 h mean dissolution rates: 5.75 ± 0.44 mg/hr (S1), 5.2 ± 0.63 mg/hr (S2), 4.55 ± 0.46 mg/hr (R) ( ± s, p < 0.01 R, S1 and S2 vs Phys, Art and EDTA; p < 0.05, S1 vs R, LSD-test). The mean percentage weight loss at 72 h was: 52.1 ± 15.75 % (S1), 44.4 ± 7.37 % (S2) and 40.5 ± 3.67 % (R) ( ± s, p < 0.01 R, S1 and S2 vs Phys, Art and EDTA, LSD-test). Diluted twice, S1 and S2 had even better effectiveness than their initial solution. The additive of Na+, K+ or Ca2+ greatly reduced the dissolution rates of S1, S2. Conclusion Our data indicate that test solutions S1 and S2 are effective solvents in the chemolysis of calcium phosphate stones. At twice dilutions, these solutions are even more useful in the treatment of stone disease. PMID:15907215

A New Extrudable Form of Hypromellose: AFFINISOL™ HPMC HME.

PubMed

Huang, Siyuan; O'Donnell, Kevin P; Keen, Justin M; Rickard, Mark A; McGinity, James W; Williams, Robert O

2016-02-01

Hypromellose is a hydrophilic polymer widely used in immediate- and modified-release oral pharmaceutical dosage forms. However, currently available grades of hypromellose are difficult, if not impossible, to process by hot melt extrusion (HME) because of their high glass transition temperature, high melt viscosity, and low degradation temperature. To overcome these challenges, a modified grade of hypromellose, AFFINISOL™ HPMC HME, was recently introduced. It has a significantly lower glass transition temperature and melt viscosity as compared to other available grades of hypromellose. The objective of this paper is to assess the extrudability and performance of AFFINISOL™ HPMC HME (100LV and 4M) as compared to other widely used polymers in HME, including HPMC 2910 100cP (the currently available hypromellose), Soluplus®, Kollidon® VA 64, and EUDRAGIT® E PO. Formulations containing polymer and carbamazepine (CBZ) were extruded on a co-rotating 16-mm twin-screw extruder, and the effect of temperature, screw speed, and feed rate was investigated. The performance of the solid dispersions was evaluated based on Flory-Huggins modeling and characterized by differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), Raman spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, and dissolution. All formulations extruded well except for HPMC 2910 100cP, which resulted in over-torqueing the extruder (machine overloading because the motor cannot provide efficient energy to rotate the shaft). Among the HME extrudates, only the EUDRAGIT® E PO formulation was crystalline as confirmed by DSC, XRD, and Raman, which agreed with predictions from Flory-Huggins modeling. Dissolution testing was conducted under both sink and non-sink conditions. Sink dissolution testing in neutral media revealed that amorphous CBZ in the HME extrudates completely dissolved within 15 min, which was much more rapid than the time for complete dissolution of bulk CBZ (60 min) and EUDRAGIT® E PO solid dispersion (more than 6 h). Non-sink dissolution in acidic media testing revealed that only CBZ contained in the AFFINISOL™ HPMC HME, and EUDRAGIT® E PO solid dispersions rapidly supersaturated after 15 min, reaching a twofold drug concentration compared to the CBZ equilibrium solubility. In summary, AFFINISOL™ HPMC HME 100LV and AFFINISOL™ HPMC HME 4M are useful in the pharmaceutical HME process to increase wetting and dissolution properties of poorly water-soluble drugs like CBZ.

Chemical stabilization of metals in mine wastes by transformed red mud and other iron compounds: laboratory tests.

PubMed

Ardau, C; Lattanzi, P; Peretti, R; Zucca, A

2014-01-01

A series of static and kinetic laboratory-scale tests were designed in order to evaluate the efficacy of transformed red mud (TRM) from bauxite refining residues, commercial zero-valent iron, and synthetic iron (III) hydroxides as sorbents/reagents to minimize the generation of acid drainage and the release of toxic elements from multi-contaminant-laden mine wastes. In particular, in some column experiments the percolation of meteoric water through a waste pile, alternated with periods of dryness, was simulated. Wastes were placed in columns together with sorbents/reagents in three different set-ups: as blended amendment (mixing method), as a bed at the bottom of the column (filtration method), or as a combination of the two previous methods. The filtration methods, which simulate the creation of a permeable reactive barrier downstream of a waste pile, are the most effective, while the use of sorbents/reagents as amendments leads to unsatisfactory results, because of the selective removal of only some contaminants. The efficacy of the filtration method is not significantly affected by the periods of dryness, except for a temporary rise of metal contents in the leachates due to dissolution of soluble salts formed upon evaporation in the dry periods. These results offer original information on advantages/limits in the use of TRM for the treatment of multi-contaminant-laden mine wastes, and represent the starting point for experimentation at larger scale.

Damage and fracture in fabric-reinforced composites under quasi-static and dynamic bending

NASA Astrophysics Data System (ADS)

Ullah, H.; Harland, A. R.; Silberschmidt, V. V.

2013-07-01

Fabric-reinforced polymer composites used in sports products can be exposed to different in-service conditions such as large deformations caused by quasi-static and dynamic loading. Composite materials subjected to such bending loads can demonstrate various damage modes - matrix cracking, delamination and, ultimately, fabric fracture. Damage evolution in composites affects both their in-service properties and performance that can deteriorate with time. Such behaviour needs adequate means of analysis and investigation, the main approaches being experimental characterisation and non-destructive examination of internal damage in composite laminates. This research deals with a deformation behaviour and damage in carbon fabric-reinforced polymer (CFRP) laminates caused by quasi-static and dynamic bending. Experimental tests were carried out to characterise the behaviour of a CFRP material under large-deflection bending, first in quasi-static and then in dynamic conditions. Izod-type impact bending tests were performed on un-notched specimens of CFRP using a Resil impactor to assess the transient response and energy absorbing capability of the material. X-ray micro computed tomography (micro-CT) was used to analyse various damage modes in the tested specimens. X-ray tomographs revealed that through-thickness matrix cracking, inter-ply and intra-ply delamination such as tow debonding, and fabric fracture were the prominent damage modes both in quasi-static and dynamic test specimens. However, the inter-ply damage was localised at impact location in dynamically tested specimens, whereas in the quasi-static specimens, it spread almost over the entire interface.

51. 500,000 POUND STATIC TEST FACILITY: CLOSEUP VIEW FROM EAST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

51. 500,000 POUND STATIC TEST FACILITY: CLOSE-UP VIEW FROM EAST SHOWING MOVABLE OBSERVATION MIRRORS WITH TRACKS - White Sands Missile Range, V-2 Rocket Facilities, Near Headquarters Area, White Sands, Dona Ana County, NM

Pile Driving Analysis for Pile Design and Quality Assurance

DOT National Transportation Integrated Search

2017-08-01

Driven piles are commonly used in foundation engineering. The most accurate measurement of pile capacity is achieved from measurements made during static load tests. Static load tests, however, may be too expensive for certain projects. In these case...

Radar cross section models for limited aspect angle windows

NASA Astrophysics Data System (ADS)

Robinson, Mark C.

1992-12-01

This thesis presents a method for building Radar Cross Section (RCS) models of aircraft based on static data taken from limited aspect angle windows. These models statistically characterize static RCS. This is done to show that a limited number of samples can be used to effectively characterize static aircraft RCS. The optimum models are determined by performing both a Kolmogorov and a Chi-Square goodness-of-fit test comparing the static RCS data with a variety of probability density functions (pdf) that are known to be effective at approximating the static RCS of aircraft. The optimum parameter estimator is also determined by the goodness of-fit tests if there is a difference in pdf parameters obtained by the Maximum Likelihood Estimator (MLE) and the Method of Moments (MoM) estimators.

How a GNSS Receiver Is Held May Affect Static Horizontal Position Accuracy

PubMed Central

Weaver, Steven A.; Ucar, Zennure; Bettinger, Pete; Merry, Krista

2015-01-01

The static horizontal position accuracy of a mapping-grade GNSS receiver was tested in two forest types over two seasons, and subsequently was tested in one forest type against open sky conditions in the winter season. The main objective was to determine whether the holding position during data collection would result in significantly different static horizontal position accuracy. Additionally, we wanted to determine whether the time of year (season), forest type, or environmental variables had an influence on accuracy. In general, the F4Devices Flint GNSS receiver was found to have mean static horizontal position accuracy levels within the ranges typically expected for this general type of receiver (3 to 5 m) when differential correction was not employed. When used under forest cover, in some cases the GNSS receiver provided a higher level of static horizontal position accuracy when held vertically, as opposed to held at an angle or horizontally (the more natural positions), perhaps due to the orientation of the antenna within the receiver, or in part due to multipath or the inability to use certain satellite signals. Therefore, due to the fact that numerous variables may affect static horizontal position accuracy, we only conclude that there is weak to moderate evidence that the results of holding position are significant. Statistical test results also suggest that the season of data collection had no significant effect on static horizontal position accuracy, and results suggest that atmospheric variables had weak correlation with horizontal position accuracy. Forest type was found to have a significant effect on static horizontal position accuracy in one aspect of one test, yet otherwise there was little evidence that forest type affected horizontal position accuracy. Since the holding position was found in some cases to be significant with regard to the static horizontal position accuracy of positions collected in forests, it may be beneficial to have an understanding of antenna positioning within the receiver to achieve the greatest accuracy during data collection. PMID:25923667

How a GNSS Receiver Is Held May Affect Static Horizontal Position Accuracy.

PubMed

Weaver, Steven A; Ucar, Zennure; Bettinger, Pete; Merry, Krista

2015-01-01

The static horizontal position accuracy of a mapping-grade GNSS receiver was tested in two forest types over two seasons, and subsequently was tested in one forest type against open sky conditions in the winter season. The main objective was to determine whether the holding position during data collection would result in significantly different static horizontal position accuracy. Additionally, we wanted to determine whether the time of year (season), forest type, or environmental variables had an influence on accuracy. In general, the F4Devices Flint GNSS receiver was found to have mean static horizontal position accuracy levels within the ranges typically expected for this general type of receiver (3 to 5 m) when differential correction was not employed. When used under forest cover, in some cases the GNSS receiver provided a higher level of static horizontal position accuracy when held vertically, as opposed to held at an angle or horizontally (the more natural positions), perhaps due to the orientation of the antenna within the receiver, or in part due to multipath or the inability to use certain satellite signals. Therefore, due to the fact that numerous variables may affect static horizontal position accuracy, we only conclude that there is weak to moderate evidence that the results of holding position are significant. Statistical test results also suggest that the season of data collection had no significant effect on static horizontal position accuracy, and results suggest that atmospheric variables had weak correlation with horizontal position accuracy. Forest type was found to have a significant effect on static horizontal position accuracy in one aspect of one test, yet otherwise there was little evidence that forest type affected horizontal position accuracy. Since the holding position was found in some cases to be significant with regard to the static horizontal position accuracy of positions collected in forests, it may be beneficial to have an understanding of antenna positioning within the receiver to achieve the greatest accuracy during data collection.

Does the Value of Dynamic Assessment in Predicting End-of-First-Grade Mathematics Performance Differ as a Function of English Language Proficiency?

PubMed Central

Seethaler, Pamela M.; Fuchs, Lynn S.; Fuchs, Douglas; Compton, Donald L.

2015-01-01

The purpose of this study was to assess the added value of dynamic assessment (DA) beyond more conventional static measures for predicting individual differences in year-end 1st-grade calculation (CA) and word-problem (WP) performance, as a function of limited English proficiency (LEP) status. At the start of 1st grade, students (129 LEP; 163 non-LEP) were assessed on a brief static mathematics test, an extended static mathematics test, static tests of domain-general abilities associated with CAs and WPs (vocabulary; reasoning), and DA. Near end of 1st grade, they were assessed on CA and WP. Regression analyses indicated that the value of the predictor depends on the predicted outcome and LEP status. In predicting CAs, the extended mathematics test and DA uniquely explained variance for LEP children, with stronger predictive value for the extended mathematics test; for non-LEP children, the extended mathematics test was the only significant predictor. However, in predicting WPs, only DA and vocabulary were uniquely predictive for LEP children, with stronger value for DA; for non-LEP children, the extended mathematics test and DA were comparably uniquely predictive. Neither the brief static mathematics test nor reasoning was significant in predicting either outcome. The potential value of a gated screening process, using an extended mathematics assessment to predict CAs and using DA to predict WPs, is discussed. PMID:26523068

Effect of solvent on in vitro dissolution: Summary of results for uranium, americium, and cobalt aerosols

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

Guilmette, R.A.; Hoover, M.D.

1995-12-01

The revised 10 CFR Part 20 has adopted the ICRP Publication 30 method for calculating the committed effective dose equivalent from intakes of radionuclides. This dosimetry scheme requires knowledge or assumptions about the chemical form of the radionuclide, its particle size, and its known or assumed solubility. The solubility is classified as being either D (relatively soluble), W, or Y (relatively insoluble), depending on whether the material dissolves over periods of days, weeks, or years. Although Nuclear Regulatory Commission licensees may wish to take advantage of material-specific knowledge in order to adjust annual limits on intake and derived air concentrations,more » relatively few radioactive materials to which workers and the general population may be exposed have been adequately characterized either in terms of physicochemical form or solubility. Experimental measurement of solubility using some type of in vitro dissolution measurement system is therefore needed. However, there is currently no clear consensus regarding the appropriate design of in vitro dissolution systems, particularly when considering the range of different radionuclides to be studied, and the complexity of the biological mechanisms involved in the retention and clearance of inhaled deposited radioactive particles. The purpose of this study was to evaluate the effect of the several solvents on the dissolution of four test aerosols ({sup 57}Co{sub 3}O{sub 4}, {sup 241}AmO{sub 2}, ammonium diuranate [ADU], and U{sub 3}O{sub 8}) selected to encompass a variety of chemical and biochemical properties in vivo. The results of this study provide some guidance on the usefulness of in vitro dissolution tests for estimating the solubility of unknown radionuclide particles within the context of a simple model such as the class D, W, and Y formulation of ICRP 30.« less

Dissolution of bovine pulp tissue in solutions consisting of varying NaOCl concentrations and combined with EDTA.

PubMed

Irala, Luis Eduardo Duarte; Grazziotin-Soares, Renata; Salles, Alexandre Azevedo; Munari, Aline Zen; Pereira, Joseani Santos

2010-01-01

This in vitro study evaluated (1) the dissolution of bovine pulp tissue in solutions consisting of varying NaOCl concentrations and combined with EDTA; and (2) the pH of these solutions before and after the experiment. The independent variables were the concentration and the volume of the solution. Thirty bovine pulps were divided in equal fragments, resulting in 90 fragments of pulp tissue. Each fragment was immersed in one of the following solutions: 1% NaOCl (4 ml), 2.5% NaOCl (4 ml), 1% NaOCl + 17% EDTA (2 ml : 2 ml), 1% NaOCl + 17% EDTA (1 ml : 3 ml), 2.5% NaOCl + 17% EDTA (2 ml : 2 ml), and 2.5% NaOCl + 17% EDTA (1 ml : 3 ml). The test solutions were dichotomized as either able or not able to dissolve the tissue, the latter being attributed when the dissolution of the pulp tissue was not complete within 48 hours. When the samples were able to dissolve the tissue, the time required for complete tissue dissolution was submitted to statistical analysis. The pH of the solutions was measured before and after the experiment. The pH variable was dichotomized as either changed or unchanged. The results demonstrated that the NaOCl solutions combined with 17% EDTA were not able to dissolve the tissue. The t-test revealed that the 2.5% NaOCl solution presented a lower mean dissolution time than the 1% NaOCl solution (p < 0.001). The pH of the solutions with equal volumes of NaOCl and EDTA decreased in 48 hours.

Effects of sinker shapes on dissolution profiles.

PubMed

Soltero, R A; Hoover, J M; Jones, T F; Standish, M

1989-01-01

In dissolution testing, according to the U.S. Pharmacopeia, a nonreactive stainless steel wire helix is typically used to sink dosage forms that would otherwise float. The objective of this investigation was to determine if other sinker shapes will influence the rate, extent, or variability of dissolution. Criteria for the optimal sinker were defined. Various new sinker designs were fabricated, tested, and classified. Four classes of sinker shapes were defined: longitudinal, lateral, screen enclosures, and internal weights. Longitudinal sinkers contact the dosage forms on the long axis. Lateral sinkers either wrap around or contact capsule dosage forms in the middle, such as the line where the top and bottom halves of a capsule shell come together. Screen enclosures are of two types: either a wire cage, which holds the entire capsule, or a circular piece of wire screen placed on top of the capsule. Internal weights consist of two steel ball bearings, one inserted into each end of the capsule. The investigation consisted of four studies: (1) visual observation of the dissolution performance using 12 different sinkers; (2) the effect on drug release from nine classified sinkers on two different capsule formulations; (3) side-by-side comparison between the selected optimal longitudinal U clip and the wire helix lateral type sinkers; and (4) hydrodynamic effects caused by the use of the longitudinal U clip and the wire helix lateral type sinkers in the absence of capsule shells. We concluded that capsules sunk with either of the two longitudinal sinkers, the U clip or the paper clip, have faster, more complete dissolution and less variable results than did lateral type sinkers.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative evaluation of human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite: An in vitro study

PubMed Central

Taneja, Sonali; Mishra, Neha; Malik, Shubhra

2014-01-01

Introduction: Irrigation plays an indispensable role in removal of tissue remnants and debris from the complicated root canal system. This study compared the human pulp tissue dissolution by different concentrations of chlorine dioxide, calcium hypochlorite and sodium hypochlorite. Materials and Methods: Pulp tissue was standardized to a weight of 9 mg for each sample. In all,60 samples obtained were divided into 6 groups according to the irrigating solution used- 2.5% sodium hypochlorite (NaOCl), 5.25% NaOCl, 5% calcium hypochlorite (Ca(OCl)2), 10% Ca(OCl)2, 5%chlorine dioxide (ClO2) and 13% ClO2. Pulp tissue was placed in each test tube carrying irrigants of measured volume (5ml) according to their specified subgroup time interval: 30 minutes (Subgroup A) and 60 minutes (Subgroup B). The solution from each sample test tube was filtered and was left for drying overnight. The residual weight was calculated by filtration method. Results: Mean tissue dissolution increases with increase in time period. Results showed 5.25% NaOCl to be most effective at both time intervals followed by 2.5% NaOCl at 60 minutes, 10%Ca(OCl)2 and 13% ClO2 at 60 minutes. Least amount of tissue dissolving ability was demonstrated by 5% Ca(OCl)2 and 5% ClO2 at 30 minutes. Distilled water showed no pulp tissue dissolution. Conclusion: Withinthe limitations of the study, NaOCl most efficiently dissolved the pulp tissue at both concentrations and at both time intervals. Mean tissue dissolution by Ca(OCl)2 and ClO2 gradually increased with time and with their increase in concentration. PMID:25506141

Antimisting kerosene: Base fuel effects, blending and quality control techniques

NASA Technical Reports Server (NTRS)

Yavrouian, A. H.; Ernest, J.; Sarohia, V.

1984-01-01

The problems associated with blending of the AMK additive with Jet A, and the base fuel effects on AMK properties are addressed. The results from the evaluation of some of the quality control techniques for AMK are presented. The principal conclusions of this investigation are: significant compositional differences for base fuel (Jet A) within the ASTM specification DI655; higher aromatic content of the base fuel was found to be beneficial for the polymer dissolution at ambient (20 C) temperature; using static mixer technology, the antimisting additive (FM-9) is in-line blended with Jet A, producing AMK which has adequate fire-protection properties 15 to 20 minutes after blending; degradability of freshly blended and equilibrated AMK indicated that maximum degradability is reached after adequate fire protection is obtained; the results of AMK degradability as measured by filter ratio, confirmed previous RAE data that power requirements to decade freshly blended AMK are significantly higher than equilibrated AMK; blending of the additive by using FM-9 concentrate in Jet A produces equilibrated AMK almost instantly; nephelometry offers a simple continuous monitoring capability and is used as a real time quality control device for AMK; and trajectory (jet thurst) and pressure drop tests are useful laboratory techniques for evaluating AMK quality.

Dissolution enhancement and mathematical modeling of removal of residual trichloroethene in sands by ozonation during flushing with micro-nano-bubble solution

NASA Astrophysics Data System (ADS)

Sung, Menghau; Teng, Chun-Hao; Yang, Tsung-Hsien

2017-07-01

Soil flushing using micro-nano-sized bubbles (MNB) in water as the flushing solution was tested in laboratory sand columns for the cleanup of residual trichloroethene (TCE) non-aqueous-phase-liquid (NAPL). Experiments considering flushing with MNB as well as ozone MNB (OZMNB) in water to treat soils contaminated with residual TCE liquid were conducted to examine effects of ozone on dissolution enhancement. The degrees of residual TCE saturation in soils, ranging from 0.44% to 7.6%, were tested. During flushings, aqueous TCE concentrations at the column exit were monitored and TCE masses remained in the columns after flushing were determined. Experimental results between runs with MNB and OZMNB in water revealed that dissolution enhancement was dependent on residual saturation conditions, and the maximum enhancement was around 9%. Governing equations consisting of three coupled partial differential equations (PDEs) were developed to model the system, and high-order finite difference (HOFD) method was employed to solve these PDEs. From mathematical modeling of reactive mass transfer under low residual saturation conditions (0.44% and 1.9%), experimental data were simulated and important controlling mechanisms were identified. It was concluded that a specific parameter pertinent to NAPL-water interfacial area in the Sherwood number had to be modified to satisfactorily describe the dissolution of TCE in the presence of MNB in water.

Elevated-Temperature Tests Under Static and Aerodynamic Conditions on Honeycomb-Core Sandwich Panels

NASA Technical Reports Server (NTRS)

Groen, Joseph M.; Johnson, Aldie E., Jr.

1959-01-01

Stainless-steel honeycomb-core sandwich panels which differed primarily in skin thicknesses were tested at elevated temperatures under static and aerodynamic conditions. The results of these tests were evaluated to determine the insulating effectiveness and structural integrity of the panels. The static radiant-heating tests were performed in front of a quartz-tube radiant heater at panel skin temperatures up to 1,5000 F. The aerodynamic tests were made in a Mach 1.4 heated blowdown wind tunnel. The tunnel temperature was augmented by additional heat supplied by a radiant heater which raised the panel surface temperature above 8000 F during air flow. Static radiant-heating tests of 2 minutes duration showed that all the panels protected the load-carrying structure about equally well. Thin-skin panels showed an advantage for this short-time test over thick-skin panels from a standpoint of weight against insulation. Permanent inelastic strains in the form of local buckles over each cell of the honeycomb core caused an increase in surface roughness. During the aero- dynamic tests all of the panels survived with little or no damage, and panel flutter did not occur.

Flowfield measurements in the NASA Lewis Research Center 9- by 15-foot low-speed wind tunnel

NASA Technical Reports Server (NTRS)

Hughes, Christopher E.

1989-01-01

An experimental investigation was conducted in the NASA Lewis 9- by 15-Foot Low-Speed Wind Tunnel to determine the flow characteristics in the test section during wind tunnel operation. In the investigation, a 20-probe horizontally-mounted Pitot-static flow survey rake was used to obtain cross-sectional total and static pressure surveys at four axial locations in the test section. At each axial location, the cross-sectional flowfield surveys were made by repositioning the Pitot-static flow survey rake vertically. In addition, a calibration of the new wind tunnel rake instrumentation, used to determine the wind tunnel operating conditions, was performed. Boundary laser surveys were made at three axial locations in the test section. The investigation was conducted at tunnel Mach numbers 0.20, 0.15, 0.10, and 0.05. The test section profile results from the investigation indicate that fairly uniform total pressure profiles (outside the test section boundary layer) and fairly uniform static pressure and Mach number profiles (away from the test section walls and downstream of the test section entrance) exist throughout in the wind tunnel test section.

Wind Tunnel to Atmospheric Mapping for Static Aeroelastic Scaling

NASA Technical Reports Server (NTRS)

Heeg, Jennifer; Spain, Charles V.; Rivera, J. A.

2004-01-01

Wind tunnel to Atmospheric Mapping (WAM) is a methodology for scaling and testing a static aeroelastic wind tunnel model. The WAM procedure employs scaling laws to define a wind tunnel model and wind tunnel test points such that the static aeroelastic flight test data and wind tunnel data will be correlated throughout the test envelopes. This methodology extends the notion that a single test condition - combination of Mach number and dynamic pressure - can be matched by wind tunnel data. The primary requirements for affecting this extension are matching flight Mach numbers, maintaining a constant dynamic pressure scale factor and setting the dynamic pressure scale factor in accordance with the stiffness scale factor. The scaling is enabled by capabilities of the NASA Langley Transonic Dynamics Tunnel (TDT) and by relaxation of scaling requirements present in the dynamic problem that are not critical to the static aeroelastic problem. The methodology is exercised in two example scaling problems: an arbitrarily scaled wing and a practical application to the scaling of the Active Aeroelastic Wing flight vehicle for testing in the TDT.

Static Force-Deflection Properties of Automobile Steering Components

DOT National Transportation Integrated Search

1987-06-01

This report provides the static force-deflection test results for 28 steering columns and 24 steering wheels used in domestic and import passener cars from model year 1975 to 1985. The steering columns and wheels tested include approzimately 90 perce...

Saturn Apollo Program

NASA Image and Video Library

1964-12-01

At the Marshall Space Flight Center (MSFC), the fuel tank assembly for the Saturn V S-IC-T (static test stage) fuel tank assembly is mated to the liquid oxygen (LOX) tank in building 4705. This stage underwent numerous static firings at the newly-built S-IC Static Test Stand at the MSFC west test area. The S-IC (first) stage used five F-1 engines that produced a total thrust of 7,500,000 pounds as each engine produced 1,500,000 pounds of thrust. The S-IC stage lifted the Saturn V vehicle and Apollo spacecraft from the launch pad.

Effects of static tensile load on the thermal expansion of Gr/PI composite material

NASA Technical Reports Server (NTRS)

Farley, G. L.

1981-01-01

The effect of static tensile load on the thermal expansion of Gr/PI composite material was measured for seven different laminate configurations. A computer program was developed which implements laminate theory in a piecewise linear fashion to predict the coupled nonlinear thermomechanical behavior. Static tensile load significantly affected the thermal expansion characteristics of the laminates tested. This effect is attributed to a fiber instability micromechanical behavior of the constituent materials. Analytical results correlated reasonably well with free thermal expansion tests (no load applied to the specimen). However, correlation was poor for tests with an applied load.

Space Shuttle SRM development. [Solid Rocket Motors

NASA Technical Reports Server (NTRS)

Brinton, B. C.; Kilminster, J. C.

1979-01-01

The successful static test of the fourth Development Space Shuttle Solid Rocket Motor (SRM) in February 1979 concluded the development testing phase of the SRM Project. Qualification and flight motors are currently being fabricated, with the first qualification motor to be static tested. Delivered thrust-time traces on all development motors were very close to predicted values, and both specific and total impulse exceeded specification requirements. 'All-up' static tests conducted with a solid rocket booster equipment on development motors achieved all test objectives. Transportation and support equipment concepts have been proven, baselining is complete, and component reusability has been demonstrated. Evolution of the SRM transportation support equipment, and special test equipment designs are reviewed, and development activities discussed. Handling and processing aspects of large, heavy components are described.

[The in vitro dissolution of total composition of the tablet of rhizomes of Ligusticum chuanxiong components and in vitro-in vivo correlation by the method of area under the absorbance-wavelength curve].

PubMed

Lai, Hong-qiang; Hu, Yue; Li, Xiao-dong

2015-06-01

To discuss the availability of evaluation on the dissolution studies of the multicomponents in traditional Chinese medicine, the in vitro dissolution of total composition of the tablet of rhizomes of Ligusticum chuanxiong components and its correlation with the in vivo were studied by the method of area under the absorbance-wavelength curve (AUAWC). Taken the tablet of rhizomes of Ligusticum chuanxiong components which is composed of sodium ferulate and ligustrazine hydrochloride as subject model, the dissolution tests were carried out with basket method. The plasma concentrations of tablets in different rats were determined by AUAWC at different interval times. The in vivo absorption percentage was calculated by Wagner-Nelson equation to evaluate the in vitro and in vivo correlation. According to the results, the cumulative dissolution in vitro of total composition of tablets of rhizomes of Ligusticum chuanxiong components at 60 min was 90.65% in water by AUAWC. The in vivo pharmacokinetics is fitted with an one-compartment model. The linear equation based on the cumulative dissolution rate (fr) and absorption percentage (fa) at 5, 10, 20, 30 and 60 min was fa = 0.819 7 fr+0.183 and the correlation coefficient was 0.959 5, which showed a good correlation between the in vitro dissolution and the in vivo absorption percentage. The method of AUAWC can be used accurately, feasibly and conveniently to evaluate the in vitro and in vivo correlation of total composition of tablets of rhizomes of Ligusticum chuanxiong components, which will provide better guidance to study the in vitro and in vivo correlation of sustained release preparation etc under complex system of traditional Chinese medicine in the future.

Eccentric Training and Static Stretching Improve Hamstring Flexibility of High School Males

PubMed Central

Bandy, William D.

2004-01-01

Objective: To determine if the flexibility of high-school-aged males would improve after a 6-week eccentric exercise program. In addition, the changes in hamstring flexibility that occurred after the eccentric program were compared with a 6-week program of static stretching and with a control group (no stretching). Design and Setting: We used a test-retest control group design in a laboratory setting. Subjects were assigned randomly to 1 of 3 groups: eccentric training, static stretching, or control. Subjects: A total of 69 subjects, with a mean age of 16.45 ± 0.96 years and with limited hamstring flexibility (defined as 20° loss of knee extension measured with the thigh held at 90° of hip flexion) were recruited for this study. Measurements: Hamstring flexibility was measured using the passive 90/90 test before and after the 6-week program. Results: Differences were significant for test and for the test-by-group interaction. Follow-up analysis indicated significant differences between the control group (gain = 1.67°) and both the eccentric-training (gain = 12.79°) and static-stretching (gain = 12.05°) groups. No difference was found between the eccentric and static-stretching groups. Conclusions: The gains achieved in range of motion of knee extension (indicating improvement in hamstring flexibility) with eccentric training were equal to those made by statically stretching the hamstring muscles. PMID:15496995

Eccentric Training and Static Stretching Improve Hamstring Flexibility of High School Males.

PubMed

Nelson, Russell T; Bandy, William D

2004-09-01

OBJECTIVE: To determine if the flexibility of high-school-aged males would improve after a 6-week eccentric exercise program. In addition, the changes in hamstring flexibility that occurred after the eccentric program were compared with a 6-week program of static stretching and with a control group (no stretching). DESIGN AND SETTING: We used a test-retest control group design in a laboratory setting. Subjects were assigned randomly to 1 of 3 groups: eccentric training, static stretching, or control. SUBJECTS: A total of 69 subjects, with a mean age of 16.45 +/- 0.96 years and with limited hamstring flexibility (defined as 20 degrees loss of knee extension measured with the thigh held at 90 degrees of hip flexion) were recruited for this study. MEASUREMENTS: Hamstring flexibility was measured using the passive 90/90 test before and after the 6-week program. RESULTS: Differences were significant for test and for the test-by-group interaction. Follow-up analysis indicated significant differences between the control group (gain = 1.67 degrees ) and both the eccentric-training (gain = 12.79 degrees ) and static-stretching (gain = 12.05 degrees ) groups. No difference was found between the eccentric and static-stretching groups. CONCLUSIONS: The gains achieved in range of motion of knee extension (indicating improvement in hamstring flexibility) with eccentric training were equal to those made by statically stretching the hamstring muscles.

In Silico Modeling Approach for the Evaluation of Gastrointestinal Dissolution, Supersaturation, and Precipitation of Posaconazole.

PubMed

Hens, Bart; Pathak, Shriram M; Mitra, Amitava; Patel, Nikunjkumar; Liu, Bo; Patel, Sanjaykumar; Jamei, Masoud; Brouwers, Joachim; Augustijns, Patrick; Turner, David B

2017-12-04

The aim of this study was to evaluate gastrointestinal (GI) dissolution, supersaturation, and precipitation of posaconazole, formulated as an acidified (pH 1.6) and neutral (pH 7.1) suspension. A physiologically based pharmacokinetic (PBPK) modeling and simulation tool was applied to simulate GI and systemic concentration-time profiles of posaconazole, which were directly compared with intraluminal and systemic data measured in humans. The Advanced Dissolution Absorption and Metabolism (ADAM) model of the Simcyp Simulator correctly simulated incomplete gastric dissolution and saturated duodenal concentrations of posaconazole in the duodenal fluids following administration of the neutral suspension. In contrast, gastric dissolution was approximately 2-fold higher after administration of the acidified suspension, which resulted in supersaturated concentrations of posaconazole upon transfer to the upper small intestine. The precipitation kinetics of posaconazole were described by two precipitation rate constants, extracted by semimechanistic modeling of a two-stage medium change in vitro dissolution test. The 2-fold difference in exposure in the duodenal compartment for the two formulations corresponded with a 2-fold difference in systemic exposure. This study demonstrated for the first time predictive in silico simulations of GI dissolution, supersaturation, and precipitation for a weakly basic compound in part informed by modeling of in vitro dissolution experiments and validated via clinical measurements in both GI fluids and plasma. Sensitivity analysis with the PBPK model indicated that the critical supersaturation ratio (CSR) and second precipitation rate constant (sPRC) are important parameters of the model. Due to the limitations of the two-stage medium change experiment the CSR was extracted directly from the clinical data. However, in vitro experiments with the BioGIT transfer system performed after completion of the in silico modeling provided an almost identical CSR to the clinical study value; this had no significant impact on the PBPK model predictions.

An investigation into the influence of experimental conditions on in vitro drug release from immediate-release tablets of levothyroxine sodium and its relation to oral bioavailability.

PubMed

Kocic, Ivana; Homsek, Irena; Dacevic, Mirjana; Parojcic, Jelena; Miljkovic, Branislava

2011-09-01

The aim of this study was to investigate the influence of experimental conditions on levothyroxine sodium release from two immediate-release tablet formulations which narrowly passed the standard requirements for bioequivalence studies. The in vivo study was conducted as randomised, single-dose, two-way cross-over pharmacokinetic study in 24 healthy subjects. The in vitro study was performed using various dissolution media, and obtained dissolution profiles were compared using the similarity factor value. Drug solubility in different media was also determined. The in vivo results showed narrowly passing bioequivalence. Considering that levothyroxine sodium is classified as Class III drug according to the Biopharmaceutics Classification System, drug bioavailability will be less sensitive to the variation in its dissolution characteristics and it can be assumed that the differences observed in vitro in some of investigated media probably do not have significant influence on the absorption process, as long as rapid and complete dissolution exists. The study results indicate that the current regulatory criteria for the value of similarity factor in comparative dissolution testing, as well as request for very rapid dissolution (more than 85% of drug dissolved in 15 min), are very restricted for immediate-release dosage forms containing highly soluble drug substance and need further investigation. The obtained results also add to the existing debate on the appropriateness of the current bioequivalence standards for levothyroxine sodium products.

Predicting the oral pharmacokinetic profiles of multiple-unit (pellet) dosage forms using a modeling and simulation approach coupled with biorelevant dissolution testing: case example diclofenac sodium.

PubMed

Kambayashi, Atsushi; Blume, Henning; Dressman, Jennifer B

2014-07-01

The objective of this research was to characterize the dissolution profile of a poorly soluble drug, diclofenac, from a commercially available multiple-unit enteric coated dosage form, Diclo-Puren® capsules, and to develop a predictive model for its oral pharmacokinetic profile. The paddle method was used to obtain the dissolution profiles of this dosage form in biorelevant media, with the exposure to simulated gastric conditions being varied in order to simulate the gastric emptying behavior of pellets. A modified Noyes-Whitney theory was subsequently fitted to the dissolution data. A physiologically-based pharmacokinetic (PBPK) model for multiple-unit dosage forms was designed using STELLA® software and coupled with the biorelevant dissolution profiles in order to simulate the plasma concentration profiles of diclofenac from Diclo-Puren® capsule in both the fasted and fed state in humans. Gastric emptying kinetics relevant to multiple-units pellets were incorporated into the PBPK model by setting up a virtual patient population to account for physiological variations in emptying kinetics. Using in vitro biorelevant dissolution coupled with in silico PBPK modeling and simulation it was possible to predict the plasma profile of this multiple-unit formulation of diclofenac after oral administration in both the fasted and fed state. This approach might be useful to predict variability in the plasma profiles for other drugs housed in multiple-unit dosage forms. Copyright © 2014 Elsevier B.V. All rights reserved.

A comparative study of spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions.

PubMed

Dontireddy, Rakesh; Crean, Abina M

2011-10-01

Poor water solubility of new chemical entities (NCEs) is one of the major challenges the pharmaceutical industry currently faces. The purpose of this study was to investigate the feasibility of freeze-drying as an alternative technique to spray-drying to produce solid dispersions of poorly water-soluble drugs. Also investigated was the use of aqueous solvent mixtures in place of pure solvent for the production of solid dispersions. Aqueous solvent systems would reduce the environmental impact of pure organic solvent systems. Spray-dried and freeze-dried hydrocortisone/polyvinyl pyrrolidone solid dispersions exhibited differences in dissolution behavior. Freeze-dried dispersions exhibited faster dissolution rates than the corresponding spray-dried dispersions. Spray-dried systems prepared using both solvent systems (20% v/v and 96% v/v ethanol) displayed similar dissolution performance despite displaying differences in glass transition temperatures (T(g)) and surface areas. All dispersions showed drug/polymer interactions indicated by positive deviations in T(g) from the predicted values calculated using the Couchman-Karasz equation. Fourier transform infrared (FTIR) spectroscopic results confirmed the conversion of crystalline drug to the amorphous in the dispersions. Stability studies were preformed at 40°C and 75% relative humidity to investigate the physical stability of prepared dispersions. Recrystallization was observed after a month and the resultant dispersions were tested for their dissolution performance to compare with the dissolution performance of the dispersions prior to the stability study. The dissolution rate of the freeze-dried dispersions remained higher than both spray-dried dispersions after storage.

Hemodynamic changes after static and dynamic exercises and treadmill stress test; different patterns in patients with primary benign exertional headache?

PubMed

Kordi, Ramin; Mazaheri, Reza; Rostami, Mohsen; Mansournia, Mohammad Ali

2012-01-01

The pathophysiology of primary benign exertional headache (EH) is not still clearly defined. Some researchers have suggested an impaired vascular response as the etiology of this disorder. In this study we investigated whether there are any differences in blood pressure (BP) and heart rate (HR) of the subjects in course of the static and dynamic exercises and the treadmill stress test between those with and without EH. From university students, 22 patients with EH (mean age: 19.8 ± 2.10, Female to Male: 7:15) and 20 normal subjects (mean age: 19.3 ± 1.97, Female: Male: 8:12) were recruited. All the subjects performed the static and dynamic exercises at 30 and 20 percent of the maximal voluntary contraction (MVC) and Bruce treadmill stress test according to the standard protocols. HR and BP of all the cases at the baseline and during and immediately after each test were measured. No significant difference was found between the mean rise of HR, systolic and diastolic BP of the subjects with and without EH in static and dynamic exercises and also treadmill stress test. It seems that between those with and without EH, there is no significant difference in rise of HR and BP response to static and dynamic exercises and treadmill stress test. Further studies are required to find the pathophysiology and risk factors of EH.

FEM Modeling of the Relationship between the High-Temperature Hardness and High-Temperature, Quasi-Static Compression Experiment.

PubMed

Zhang, Tao; Jiang, Feng; Yan, Lan; Xu, Xipeng

2017-12-26

The high-temperature hardness test has a wide range of applications, but lacks test standards. The purpose of this study is to develop a finite element method (FEM) model of the relationship between the high-temperature hardness and high-temperature, quasi-static compression experiment, which is a mature test technology with test standards. A high-temperature, quasi-static compression test and a high-temperature hardness test were carried out. The relationship between the high-temperature, quasi-static compression test results and the high-temperature hardness test results was built by the development of a high-temperature indentation finite element (FE) simulation. The simulated and experimental results of high-temperature hardness have been compared, verifying the accuracy of the high-temperature indentation FE simulation.The simulated results show that the high temperature hardness basically does not change with the change of load when the pile-up of material during indentation is ignored. The simulated and experimental results show that the decrease in hardness and thermal softening are consistent. The strain and stress of indentation were analyzed from the simulated contour. It was found that the strain increases with the increase of the test temperature, and the stress decreases with the increase of the test temperature.

FEM Modeling of the Relationship between the High-Temperature Hardness and High-Temperature, Quasi-Static Compression Experiment

PubMed Central

Zhang, Tao; Jiang, Feng; Yan, Lan; Xu, Xipeng

2017-01-01

The high-temperature hardness test has a wide range of applications, but lacks test standards. The purpose of this study is to develop a finite element method (FEM) model of the relationship between the high-temperature hardness and high-temperature, quasi-static compression experiment, which is a mature test technology with test standards. A high-temperature, quasi-static compression test and a high-temperature hardness test were carried out. The relationship between the high-temperature, quasi-static compression test results and the high-temperature hardness test results was built by the development of a high-temperature indentation finite element (FE) simulation. The simulated and experimental results of high-temperature hardness have been compared, verifying the accuracy of the high-temperature indentation FE simulation.The simulated results show that the high temperature hardness basically does not change with the change of load when the pile-up of material during indentation is ignored. The simulated and experimental results show that the decrease in hardness and thermal softening are consistent. The strain and stress of indentation were analyzed from the simulated contour. It was found that the strain increases with the increase of the test temperature, and the stress decreases with the increase of the test temperature. PMID:29278398

[Research progress on mechanical performance evaluation of artificial intervertebral disc].

PubMed

Li, Rui; Wang, Song; Liao, Zhenhua; Liu, Weiqiang

2018-03-01

The mechanical properties of artificial intervertebral disc (AID) are related to long-term reliability of prosthesis. There are three testing methods involved in the mechanical performance evaluation of AID based on different tools: the testing method using mechanical simulator, in vitro specimen testing method and finite element analysis method. In this study, the testing standard, testing equipment and materials of AID were firstly introduced. Then, the present status of AID static mechanical properties test (static axial compression, static axial compression-shear), dynamic mechanical properties test (dynamic axial compression, dynamic axial compression-shear), creep and stress relaxation test, device pushout test, core pushout test, subsidence test, etc. were focused on. The experimental techniques using in vitro specimen testing method and testing results of available artificial discs were summarized. The experimental methods and research status of finite element analysis were also summarized. Finally, the research trends of AID mechanical performance evaluation were forecasted. The simulator, load, dynamic cycle, motion mode, specimen and test standard would be important research fields in the future.

Fractionation of iron isotopes during leaching of natural particles by acidic and circumneutral leaches and development of an optimal leach for marine particulate iron isotopes

NASA Astrophysics Data System (ADS)

Revels, Brandi N.; Zhang, Ruifeng; Adkins, Jess F.; John, Seth G.

2015-10-01

Iron (Fe) is an essential nutrient for life on land and in the oceans. Iron stable isotope ratios (δ56Fe) can be used to study the biogeochemical cycling of Fe between particulate and dissolved phases in terrestrial and marine environments. We have investigated the dissolution of Fe from natural particles both to understand the mechanisms of Fe dissolution, and to choose a leach appropriate for extracting labile Fe phases of marine particles. With a goal of finding leaches which would be appropriate for studying dissolved-particle interactions in an oxic water column, three particle types were chosen including oxic seafloor sediments (MESS-3), terrestrial dust (Arizona Test Dust - A2 Fine), and ocean sediment trap material from the Cariaco basin. Four leaches were tested, including three acidic leaches similar to leaches previously applied to marine particles and sediments (25% acetic acid, 0.01 N HCl, and 0.5 N HCl) and a pH 8 oxalate-EDTA leach meant to mimic the dissolution of particles by organic complexation, as occurs in natural seawater. Each leach was applied for three different times (10 min, 2 h, 24 h) at three different temperatures (25 °C, 60 °C, 90 °C). MESS-3 was also leached under various redox conditions (0.02 M hydroxylamine hydrochloride or 0.02 M hydrogen peroxide). For all three sample types tested, we find a consistent relationship between the amount of Fe leached and leachate δ56Fe for all of the acidic leaches, and a different relationship between the amount of Fe leached and leachate δ56Fe for the oxalate-EDTA leach, suggesting that Fe was released through proton-promoted dissolution for all acidic leaches and by ligand-promoted dissolution for the oxalate-EDTA leach. Fe isotope fractionations of up to 2‰ were observed during acidic leaching of MESS-3 and Cariaco sediment trap material, but not for Arizona Test Dust, suggesting that sample composition influences fractionation, perhaps because Fe isotopes are greatly fractionated during leaching of silicates and clays but only minimally fractionated during dissolution of Fe oxyhydroxides. Two different analytical models were developed to explain the relationship between amount of Fe leached and δ56Fe, one of which assumes mixing between two Fe phases with different δ56Fe and different dissolution rates, and the other of which assumes dissolution of a single phase with a kinetic isotope effect. We apply both models to fit results from the acidic leaches of MESS-3 and find that the fit for both models is very similar, suggesting that isotope data will never be sufficient to distinguish between these two processes for natural materials. Next, we utilize our data to choose an optimal leach for application to marine particles. The oxalate-EDTA leach is well-suited to this purpose because it does not greatly fractionate Fe isotopes for a diversity of particle types over a wide variety of leaching conditions, and because it approximates the conditions by which particulate Fe dissolves in the oceans. We recommend a 2 h leach at 90 °C with 0.1 M oxalate and 0.05 M EDTA at pH 8 to measure labile ;ligand-leachable; particulate δ56Fe on natural marine materials with a range of compositions.

Fatigue and quasi-static mechanical behavior of bio-degradable porous biomaterials based on magnesium alloys.

PubMed

Hedayati, R; Ahmadi, S M; Lietaert, K; Tümer, N; Li, Y; Amin Yavari, S; Zadpoor, A A

2018-07-01

Magnesium and its alloys have the intrinsic capability of degrading over time in vivo without leaving toxic degradation products. They are therefore suitable for use as biodegradable scaffolds that are replaced by the regenerated tissues. One of the main concerns for such applications, particularly in load-bearing areas, is the sufficient mechanical integrity of the scaffold before sufficient volumes of de novo tissue is generated. In the majority of the previous studies on the effects of biodegradation on the mechanical properties of porous biomaterials, the change in the elastic modulus has been studied. In this study, variations in the static and fatigue mechanical behavior of porous structures made of two different Mg alloys (AZ63 and M2) over different dissolution times ( 6, 12, and 24 h) have been investigated. The results showed an increase in the mechanical properties obtained from stress-strain curve (elastic modulus, yield stress, plateau stress, and energy absorption) after 6-12 h and a sharp decrease after 24 h. The initial increase in the mechanical properties may be attributed to the accumulation of corrosion products in the pores of the porous structure before degradation has considerably proceeded. The effects of mineral deposition was more pronounced for the elastic modulus as compared to other mechanical properties. That may be due to insufficient integration of the deposited particles in the structure of the magnesium alloys. While the bonding of the parts being combined in a composite-like material is of great importance in determining its yield stress, the effects of bonding strength of both parts is much lower in determining the elastic modulus. The results of the current study also showed that the dissolution rates of the studied Mg alloys were too high for direct use in human body. © 2018 Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1798-1811, 2018. © 2018 Authors Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.

Dissolution enhancement of a model poorly water-soluble drug, atorvastatin, with ordered mesoporous silica: comparison of MSF with SBA-15 as drug carriers.

PubMed

Maleki, Aziz; Hamidi, Mehrdad

2016-01-01

The purpose of this study was to develop mesoporous silica materials incorporated with poorly water-soluble drug atorvastatin calcium (AC) in order to improve drug dissolution, and intended to be orally administrated. A comparison between 2D-hexagonal silica nanostructured SBA-15 and mesocellular siliceous foam (MSF) with continuous 3D pore system on drug release rate was investigated. AC-loaded mesoporous silicas were characterized thorough N2 adsorption-desorption analysis, Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and dynamic light scattering (DLS). Results demonstrated a successful incorporation of AC into the silica-based hosts. The results taken from the drug release tests were also analyzed using different parameters, namely similarity factor (f2), difference factor (f1), dissolution efficiency (DE%), mean dissolution rate (MDR) and dissolution time (tm%). It confirmed a significant enhancement in the release profile of atorvastatin calcium with SBA-15, and MSF as drug carrier. Moreover, in comparison with SBA-15, MSF showed faster release rate of AC in enzyme-free simulated gastric fluid (pH 1.2). We believed that our findings can help the use of mesoporous silica materials in improving bioavailability of poorly water-soluble drugs.

Testing signal enhancement mechanisms in the dissolution NMR of acetone

NASA Astrophysics Data System (ADS)

Alonso-Valdesueiro, Javier; Elliott, Stuart J.; Bengs, Christian; Meier, Benno; Levitt, Malcolm H.

2018-01-01

In cryogenic dissolution NMR experiments, a substance of interest is allowed to rest in a strong magnetic field at cryogenic temperature, before dissolving the substance in a warm solvent, transferring it to a high-resolution NMR spectrometer, and observing the solution-state NMR spectrum. In some cases, negative enhancements of the 13C NMR signals are observed, which have been attributed to quantum-rotor-induced polarization. We show that in the case of acetone (propan-2-one) the negative signal enhancements of the methyl 13C sites may be understood by invoking conventional cross-relaxation within the methyl groups. The 1H nuclei acquire a relative large net polarization through thermal equilibration in a magnetic field at low temperature, facilitated by the methyl rotation which acts as a relaxation sink; after dissolution, the 1H magnetization slowly returns to thermal equilibrium at high temperature, in part by cross-relaxation processes, which induce a transient negative polarization of nearby 13C nuclei. We provide evidence for this mechanism experimentally and theoretically by saturating the 1H magnetization using a radiofrequency field pulse sequence before dissolution and comparing the 13 C magnetization evolution after dissolution with the results obtained from a conventional 1 H-13 C cross relaxation model of the CH3 moieties in acetone.

Optimization of limestone drains for long- term treatment of acidic mine drainage, Swatara Creek Basin, Schuylkill County, PA

USGS Publications Warehouse

Cravotta, Charles A.; Ward, S.J.; Koury, Daniel J.; Koch, R.D.

2004-01-01

Limestone drains were constructed in 1995, 1997, and 2000 to treat acidic mine drainage (AMD) from the Orchard, Buck Mtn., and Hegins discharges, respectively, in the Swatara Creek Basin, Southern Anthracite Coalfield, east-central Pennsylvania. This report summarizes the construction characteristics and performance of each of the limestone drains on the basis of influent and effluent quality and laboratory tests of variables affecting limestone dissolution rates. Data for influent and effluent indicate substantial alkalinity production by the Orchard and Buck Mtn. limestone drains and only marginal benefits from the Hegins drain. Nevertheless, the annual alkalinity loading rates have progressively declined with age of all three systems. Collapsible-container (cubitainer) testing was conducted to evaluate current scenarios and possible options for reconstruction and maintenance of the limestone drains to optimize their long-term performance. The cubitainer tests indicated dissolution rates for the current configurations that were in agreement with field flux data (net loading) for alkalinity and dissolved calcium. The dissolution rates in cubitainers were larger for closed conditions than open conditions, but the rates were comparable for coated and uncoated limestone for a given condition. Models developed on the basis of the cubitainer testing indicate (1) exponential declines in limestone mass and corresponding alkalinity loading rates with increased age of limestone drains and (2) potential for improved performance with enlargement, complete burial, and/or regular flushing of the systems.

The pH-dependent release of platinum group elements (PGEs) from gasoline and diesel fuel catalysts: Implication for weathering in soils.

PubMed

Suchá, Veronika; Mihaljevič, Martin; Ettler, Vojtěch; Strnad, Ladislav

2016-04-15

Powdered samples of new and old gasoline catalysts (Pt, Pd, Rh) and new and old diesel (Pt) catalysts were subjected to a pH-static leaching procedure (pH 2-9) coupled with thermodynamic modeling using PHREEQC-3 to verify the release and mobility of PGEs (platinum group elements). PGEs were released under acidic conditions, mostly exhibiting L-shaped leaching patterns: diesel old: 5.47, 0.005, 0.02; diesel new: 68.5, 0.23, 0.11; gasoline old: 0.1, 11.8, 4.79; gasoline new 2.6, 25.2, 35.9 in mg kg(-1) for Pt, Pd and Rh, respectively. Only the new diesel catalyst had a strikingly different leaching pattern with elevated concentrations at pH 4, probably influenced by the dissolution of the catalyst carrier and washcoat. The pH-static experiment coupled with thermodynamic modeling was found to be an effective instrument for understanding the leaching behavior of PGEs under various environmental conditions, and indicated that charged Pt and Rh species may be adsorbed on the negatively charged surface of kaolinite or Mn oxides in the soil system, whereas uncharged Pd and Rh species may remain mobile in soil solutions. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Use of Interactive Computer Animations Based on POE as a Presentation Tool in Primary Science Teaching

NASA Astrophysics Data System (ADS)

Akpınar, Ercan

2014-08-01

This study investigates the effects of using interactive computer animations based on predict-observe-explain (POE) as a presentation tool on primary school students' understanding of the static electricity concepts. A quasi-experimental pre-test/post-test control group design was utilized in this study. The experiment group consisted of 30 students, and the control group of 27 students. The control group received normal instruction in which the teacher provided instruction by means of lecture, discussion and homework. Whereas in the experiment group, dynamic and interactive animations based on POE were used as a presentation tool. Data collection tools used in the study were static electricity concept test and open-ended questions. The static electricity concept test was used as pre-test before the implementation, as post-test at the end of the implementation and as delay test approximately 6 weeks after the implementation. Open-ended questions were used at the end of the implementation and approximately 6 weeks after the implementation. Results indicated that the interactive animations used as presentation tools were more effective on the students' understanding of static electricity concepts compared to normal instruction.

Characterization of Triaxial Braided Composite Material Properties for Impact Simulation

NASA Technical Reports Server (NTRS)

Roberts, Gary D.; Goldberg, Robert K.; Biniendak, Wieslaw K.; Arnold, William A.; Littell, Justin D.; Kohlman, Lee W.

2009-01-01

The reliability of impact simulations for aircraft components made with triaxial braided carbon fiber composites is currently limited by inadequate material property data and lack of validated material models for analysis. Improvements to standard quasi-static test methods are needed to account for the large unit cell size and localized damage within the unit cell. The deformation and damage of a triaxial braided composite material was examined using standard quasi-static in-plane tension, compression, and shear tests. Some modifications to standard test specimen geometries are suggested, and methods for measuring the local strain at the onset of failure within the braid unit cell are presented. Deformation and damage at higher strain rates is examined using ballistic impact tests on 61- by 61- by 3.2-mm (24- by 24- by 0.125-in.) composite panels. Digital image correlation techniques were used to examine full-field deformation and damage during both quasi-static and impact tests. An impact analysis method is presented that utilizes both local and global deformation and failure information from the quasi-static tests as input for impact simulations. Improvements that are needed in test and analysis methods for better predictive capability are examined.

Performance characteristics of axisymmetric convergent-divergent exhaust nozzles with longitudinal slots in the divergent

NASA Technical Reports Server (NTRS)

Leavitt, L. D.; Bangert, L. S.

1982-01-01

An investigation was conducted in the Langley 16 foot Transonic Tunnel and in the static test facility of that tunnel to determine the effects of divergent flap ventilation of an axisymmetric nozzle on nozzle internal (static) and wind on performance. Tests were conducted at 0 deg angle of attack at static conditions and at Mach numbers from 0.6 to 1.2. Ratios of jet total pressure to free stream static pressure were varied from 1.0 (jet off) to approximately 14.0 depending on Mach number. The results of this study indicate that divergent flap ventilation generally provided large performance benefits at overexpanded nozzle conditions and performance reductions at underexpanded nozzle conditions when compared to the baseline (unventilated) nozzles. Ventilation also reduced the peak static and wind on performance levels.

Enhancing the bioavailability of mebendazole by integrating the principles solid dispersion and nanocrystal techniques, for safe and effective management of human echinococcosis.

PubMed

Chaudhary, Sushant; Garg, Tarun; Rath, Goutam; Murthy, Rs Rayasa; Goyal, Amit K

2016-05-01

The method based on integrating the principles of solid dispersion and nanocrystal techniques was developed to prepare polymer crystals (PCs) of mebendazole (MBZ) and polyethylene glycol (PEG). Powder X-Ray diffraction (PXRD) of the PC crystals shows the required integrated crystalline and amorphous regions. The in vitro solubility studies showed a 32-fold increase in the solubility of the drug. Tests of dissolution of the PCs showed that the crystals have an enhanced dissolution rate in comparison to those in the MF. The results of the pharmacokinetic study showed a 2.12-fold increase in the bioavailability of the drug. Thus, the present study has proved the potential in enhancing solubility, dissolution, and bioavailability of the drug.

Measuring Cognitive Load in Test Items: Static Graphics versus Animated Graphics

ERIC Educational Resources Information Center

Dindar, M.; Kabakçi Yurdakul, I.; Inan Dönmez, F.

2015-01-01

The majority of multimedia learning studies focus on the use of graphics in learning process but very few of them examine the role of graphics in testing students' knowledge. This study investigates the use of static graphics versus animated graphics in a computer-based English achievement test from a cognitive load theory perspective. Three…

Biowaiver extension potential and IVIVC for BCS Class II drugs by formulation design: Case study for cyclosporine self-microemulsifying formulation.

PubMed

Yang, Su-Geun

2010-11-01

The objective of this work was to suggest the biowaiver potential of biopharmaceutical classification system (BCS) Class II drugs in self-microemulsifying drug delivery systems (SMEDDS) which are known to increase the solubility, dissolution and oral absorption of water-insoluble drugs. Cyclosporine was selected as a representative BCS Class II drug. New generic candidate of cyclosporine SMEDDS (test) was applied for the study with brand SMEDDS (reference I) and cyclosporine self-emulsifying drug delivery systems (SEDDS, reference II). Solubility and dissolution of cyclosporine from SMEDDS were critically enhanced, which were the similar behaviors with BCS class I drug. The test showed the identical dissolution rate and the equivalent bioavailability (0.34, 0.42 and 0.68 of p values for AUC₀(→)₂₄(h), C(max) and T(max), respectively) with the reference I. Based on the results, level A in vitro-in vivo correlation (IVIVC) was established from these two SMEDDS formulations. This study serves as a good example for speculating the biowaiver extension potential of BCS Class II drugs specifically in solubilizing formulation such as SMEDDS.

Uranium Anodic Dissolution under Slightly Alkaline Conditions Progress Report Full-Scale Demonstration with DU Foil

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

Gelis, A.; Brown, M. A.; Wiedmeyer, S.

2014-02-18

Argonne National Laboratory (Argonne) is developing an alternative method for digesting irradiated low enriched uranium (LEU) foil targets to produce 99Mo in neutral/alkaline media. This method consists of the electrolytic dissolution of irradiated uranium foil in sodium bicarbonate solution, followed by precipitation of base-insoluble fission and activation products, and uranyl-carbonate species with CaO. The addition of CaO is vital for the effective anion exchange separation of 99MoO 4 2- from the fission products, since most of the interfering anions (e.g., CO 3 2-) are removed from the solution, while molybdate remains in solution. An anion exchange is used to retainmore » and to purify the 99Mo from the filtrate. The electrochemical dissolver has been designed and fabricated in 304 stainless-steel (SS), and tested for the dissolution of a full-size depleted uranium (DU) target, wrapped in Al foil. Future work will include testing with low-burn-up DU foil at Argonne and later with high-burn-up LEU foils at Oak Ridge National Laboratory.« less

Dissolution and aggregation of Cu nanoparticles in culture media: effects of incubation temperature and particles size

NASA Astrophysics Data System (ADS)

Li, Lingxiangyu; Fernández-Cruz, María Luisa; Connolly, Mona; Schuster, Michael; Navas, José María

2015-01-01

Here, the effects of incubation temperature and particle size on the dissolution and aggregation behavior of copper nanoparticles (CuNPs) in culture media were investigated over 96 h, equivalent to the time period for acute cell toxicity tests. Three CuNPs with the nominal sizes of 25, 50, and 100 nm and one type of micro-sized particles (MPs, 500 nm) were examined in culture media used for human and fish hepatoma cell lines acute tests. A large decrease in sizes of CuNPs in the culture media was observed in the first 24 h incubation, and subsequently the sizes of CuNPs changed slightly over the following 72 h. Moreover, the decreasing rate in size was significantly dependent on the incubation temperature; the higher the incubation temperature, the larger the decreasing rate in size. In addition to that, we also found that the release of copper ions depended on the incubation temperature. Moreover, the dissolution rate of Cu particles increased very fast in the first 24 h, with a slight increase over the following 72 h.

Fluid mechanics of dynamic stall. II - Prediction of full scale characteristics

NASA Technical Reports Server (NTRS)

Ericsson, L. E.; Reding, J. P.

1988-01-01

Analytical extrapolations are made from experimental subscale dynamics to predict full scale characteristics of dynamic stall. The method proceeds by establishing analytic relationships between dynamic and static aerodynamic characteristics induced by viscous flow effects. The method is then validated by predicting dynamic test results on the basis of corresponding static test data obtained at the same subscale flow conditions, and the effect of Reynolds number on the static aerodynamic characteristics are determined from subscale to full scale flow conditions.

Static electricity: A literature review

NASA Astrophysics Data System (ADS)

Crow, Rita M.

1991-11-01

The major concern with static electricity is its discharging in a flammable atmosphere which can explode and cause a fire. Textile materials can have their electrical resistivity decreased by the addition of antistatic finishes, imbedding conductive particles into the fibres or by adding metal fibers to the yarns. The test methods used in the studies of static electricity include measuring the static properties of materials, of clothed persons, and of the ignition energy of flammable gases. Surveys have shown that there is sparse evidence for fires definitively being caused by static electricity. However, the 'worst-case' philosophy has been adopted and a static electricity safety code is described, including correct grounding procedures and the wearing of anti-static clothing and footwear.

CO 2-induced chemo-mechanical alteration in reservoir rocks assessed via batch reaction experiments and scratch testing

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

Aman, Michael; Espinoza, D. Nicolas; Ilgen, Anastasia G.

Here, the injection of carbon dioxide (CO 2) into geological formations results in a chemical re-equilibration between the mineral assemblage and the pore fluid, with ensuing mineral dissolution and re-precipitation. Hence, target rock formations may exhibit changes of mechanical and petrophysical properties due to CO 2 exposure. We conducted batch reaction experiments with Entrada Sandstone and Summerville Siltstone exposed to de-ionized water and synthetic brine under reservoir pressure (9–10 MPa) and temperature (80°C) for up to four weeks. Samples originate from the Crystal Geyser field site, where a naturally occurring CO 2 seepage alters portions of these geologic formations. Wemore » conducted micro-scratch tests on rock samples without alteration, altered under laboratory conditions, and naturally altered over geologic time. Scratch toughness and hardness decrease as a function of exposure time and water salinity up to 52% in the case of Entrada and 87% in the case of Summerville after CO 2-induced alteration in the laboratory. Imaging of altered cores with SEM-EDS and X-ray microCT methods show dissolution of carbonate and silica cements and matrix accompanied by minor dissolution of Fe-oxides, clays, and other silicates. Parallel experiments using powdered samples confirm that dissolution of carbonate and silica are the primary reactions. The batch reaction experiments in the autoclave utilize a high fluid to rock volume ratio and represent an end member of possible alteration associated with CO 2 storage systems. These types of tests serve as a pre-screening tool to identify the susceptibility of rock facies to CO 2-related chemical-mechanical alteration during long-term CO 2 storage.« less

Pulp tissue dissolution capacity of QMix 2in1 irrigation solution.

PubMed

Arslan, Dilara; Guneser, Mehmet Burak; Kustarci, Alper; Er, Kursat; Siso, Seyda Herguner

2015-01-01

The aim of this study was to evaluate the tissue dissolution efficacy of four root canal irrigation solutions (sodium hypochlorite [NaOCl], chlorhexidine gluconate [CHX], Octenidine [OCT], and QMix 2in1) on bovine pulp tissue. Fifty bovine pulp tissue samples, each weighing 6.55 mg, were prepared and randomly divided into four experimental groups and one control group (n = 10) according to the dissolution irrigants used: (1) 5.25% NaOCl group; (2) 2% CHX group; (3) OCT group; (4) QMix 2in1 group; and (5) control group (saline solution). These samples were then placed into special bovine dentin reservoir models and immersed for 1 h with each test solution (0.1 mL of each) at room temperature. The pulp samples were then blotted dry and weighed again. The percentage of weight loss was calculated. Statistically analyzed with one-way analysis of variance and post-hoc Tukey tests (P = 0.05). Saline solution did not dissolve the bovine pulp tissue. All groups, except OCT, dissolved pulp samples more effectively than the control group (P < 0.05). The highest tissue dissolution was observed in 5.25% NaOCl group (P < 0.05). No statistically significant difference was found between the tissue-dissolving effect between QMix 2in1 and those of 2% CHX. Within the limitations of this in vitro study, NaOCl exhibited the best tissue-dissolving effect out of all solutions tested. CHX and QMix 2in1 were able to dissolve pulp tissue but less than NaOCl. OCT and saline solutions could not exhibit significantly tissue-dissolving effectiveness. This study shown that QMix 2in1 has little capacity to dissolve pulp tissue therefore used alone is not sufficient for this purpose.

Biocompatibility of “On-Command” Dissolvable Tympanostomy Tube in the Rat Model

PubMed Central

Mai, Johnny P.; Dumont, Matthieu; Rossi, Christopher; Cleary, Kevin; Wiedermann, Joshua; Reilly, Brian K.

2016-01-01

Objectives/Hypothesis A prototype tympanostomy tube, composed of (polybutyl/methyl methacrylate-co-dimethyl amino ethyl methacrylate (PBM)), was tested to (1) evaluate the effect of PBM tubes on rat dermis as a corollary for biocompatibility and (2) to observe the efficacy of dissolution with isopropyl alcohol (iPrOH) and ethanol (EtOH). Subjects and Methods A two-part study was conducted to assess biocompatible substance with inducible dissolvability as a critical characteristic for a newly engineered tympanostomy tube. First, tympanostomy tubes were inserted subcutaneously in 10 rats, which served as an animal model for biosafety and compared to traditional tubes with respect to histologic reaction. Tissue surrounding the PBM prototype tubes was submitted for histopathology and demonstrated no tissue reactivity or signs of major inflammation. In the second part, we evaluated the dissolvability of the tube with either isopropyl alcohol, ethanol, ofloxacin, ciprodex, water, and soapy water. PBM tubes were exposed to decreasing concentrations of iPrOH and EtOH with interval qualitative assessment of dissolution. Results (1) Histologic examination did not reveal pathology with PBM tubes; (2) Concentrations of at least 50% iPrOH and EtOH dissolve PBM tubes within 48 hours while concentrations of at least 75% iPrOH and EtOH were required for dissolution when exposure was limited to four 20-minute intervals. Conclusion PBM is biocompatible in the rat model. Additionally, PBM demonstrates rapid dissolution upon alcohol-based stimuli, validating the proof-of-concept of dissolvable “on-command” or biocommandible ear tubes. Further testing of PBM is needed with a less ototoxic dissolver and in a better simulated middle ear environment, before testing can be performed in humans. PMID:27796039

Pulp tissue dissolution capacity of QMix 2in1 irrigation solution

PubMed Central

Arslan, Dilara; Guneser, Mehmet Burak; Kustarci, Alper; Er, Kursat; Siso, Seyda Herguner

2015-01-01

Objective: The aim of this study was to evaluate the tissue dissolution efficacy of four root canal irrigation solutions (sodium hypochlorite [NaOCl], chlorhexidine gluconate [CHX], Octenidine [OCT], and QMix 2in1) on bovine pulp tissue. Materials and Methods: Fifty bovine pulp tissue samples, each weighing 6.55 mg, were prepared and randomly divided into four experimental groups and one control group (n = 10) according to the dissolution irrigants used: (1) 5.25% NaOCl group; (2) 2% CHX group; (3) OCT group; (4) QMix 2in1 group; and (5) control group (saline solution). These samples were then placed into special bovine dentin reservoir models and immersed for 1 h with each test solution (0.1 mL of each) at room temperature. The pulp samples were then blotted dry and weighed again. The percentage of weight loss was calculated. Statistically analyzed with one-way analysis of variance and post-hoc Tukey tests (P = 0.05). Results: Saline solution did not dissolve the bovine pulp tissue. All groups, except OCT, dissolved pulp samples more effectively than the control group (P < 0.05). The highest tissue dissolution was observed in 5.25% NaOCl group (P < 0.05). No statistically significant difference was found between the tissue-dissolving effect between QMix 2in1 and those of 2% CHX. Conclusions: Within the limitations of this in vitro study, NaOCl exhibited the best tissue-dissolving effect out of all solutions tested. CHX and QMix 2in1 were able to dissolve pulp tissue but less than NaOCl. OCT and saline solutions could not exhibit significantly tissue-dissolving effectiveness. This study shown that QMix 2in1 has little capacity to dissolve pulp tissue therefore used alone is not sufficient for this purpose. PMID:26430374

Tank 26F-2F Evaporator Study

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

Adu-Wusu, K.

2012-12-19

Tank 26F supernate sample was sent by Savannah River Remediation to Savannah River National Laboratory for evaporation test to help understand the underlying cause of the recent gravity drain line (GDL) pluggage during operation of the 2F Evaporator system. The supernate sample was characterized prior to the evaporation test. The evaporation test involved boiling the supernate in an open beaker until the density of the concentrate (evaporation product) was between 1.4 to 1.5 g/mL. It was followed by filtering and washing of the precipitated solids with deionized water. The concentrate supernate (or concentrate filtrate), the damp unwashed precipitated solids, andmore » the wash filtrates were characterized. All the precipitated solids dissolved during water washing. A semi-quantitative X-ray diffraction (XRD) analysis on the unwashed precipitated solids revealed their composition. All the compounds with the exception of silica (silicon oxide) are known to be readily soluble in water. Hence, their dissolution during water washing is not unexpected. Even though silica is a sparingly water-soluble compound, its dissolution is also not surprising. This stems from its small fraction in the solids as a whole and also its relative freshness. Assuming similar supernate characteristics, flushing the GDL with water (preferably warm) should facilitate dissolution and removal of future pluggage events as long as build up/aging of the sparingly soluble constituent (silica) is limited. On the other hand, since the amount of silica formed is relatively small, it is quite possible dissolution of the more soluble larger fraction will cause disintegration or fragmentation of the sparingly soluble smaller fraction (that may be embedded in the larger soluble solid mass) and allow its removal via suspension in the flushing water.« less

CO 2-induced chemo-mechanical alteration in reservoir rocks assessed via batch reaction experiments and scratch testing

DOE PAGES

Aman, Michael; Espinoza, D. Nicolas; Ilgen, Anastasia G.; ...

2017-09-22

Here, the injection of carbon dioxide (CO 2) into geological formations results in a chemical re-equilibration between the mineral assemblage and the pore fluid, with ensuing mineral dissolution and re-precipitation. Hence, target rock formations may exhibit changes of mechanical and petrophysical properties due to CO 2 exposure. We conducted batch reaction experiments with Entrada Sandstone and Summerville Siltstone exposed to de-ionized water and synthetic brine under reservoir pressure (9–10 MPa) and temperature (80°C) for up to four weeks. Samples originate from the Crystal Geyser field site, where a naturally occurring CO 2 seepage alters portions of these geologic formations. Wemore » conducted micro-scratch tests on rock samples without alteration, altered under laboratory conditions, and naturally altered over geologic time. Scratch toughness and hardness decrease as a function of exposure time and water salinity up to 52% in the case of Entrada and 87% in the case of Summerville after CO 2-induced alteration in the laboratory. Imaging of altered cores with SEM-EDS and X-ray microCT methods show dissolution of carbonate and silica cements and matrix accompanied by minor dissolution of Fe-oxides, clays, and other silicates. Parallel experiments using powdered samples confirm that dissolution of carbonate and silica are the primary reactions. The batch reaction experiments in the autoclave utilize a high fluid to rock volume ratio and represent an end member of possible alteration associated with CO 2 storage systems. These types of tests serve as a pre-screening tool to identify the susceptibility of rock facies to CO 2-related chemical-mechanical alteration during long-term CO 2 storage.« less

Static pile load tests on driven piles into Intermediate-Geo Materials.

DOT National Transportation Integrated Search

2016-09-01

The Wisconsin Department of Transportation (WisDOT) has concerns with both predicting pile lengths and pile capacities for H-piles driven into Intermediate-Geo Materials (IGM). The goal of the research was to perform 7 static axial load tests at 7 lo...

The effect of electrolytes on dolomite dissolution: nanoscale observations using in situ Atomic Force Microscopy

NASA Astrophysics Data System (ADS)

Urosevic, Maja; Ruiz-Agudo, Encarnacion; Putnis, Christine V.; Cardell, Carolina; Rodriguez-Navarro, Carlos; Putnis, Andrew

2010-05-01

Dissolution of carbonate minerals is one of the main chemical reactions occurring at shallow levels in the crust of the Earth and has a paramount importance for a wide range of geological and biological processes. Calcite (CaCO3), and to a lesser extent dolomite (CaMg(CO3)2), are the major carbonate minerals in sedimentary rocks and building stone materials. The dissolution of calcite has been thoroughly investigated over a range of conditions and solution compositions. In contrast, dolomite dissolution studies have been traditionally hampered by its low reaction rates compared to calcite and its poorly constrained relationship between cation ordering and reactivity (Morse and Arvidson, 2002). Yet important questions like the so-called 'dolomite problem' (e.g. Higgins and Hu, 2005) remain unresolved and more experimental work is needed in order to understand the role of other dissolved species, such as soluble salts, on the kinetics and mechanism of dolomite dissolution and precipitation. We have explored the effect of different electrolytes on the dissolution rate of dolomite by using in situ Atomic Force Microcopy (AFM). Experiments were carried out by passing alkali halide, nitrate and sulfate salt solutions (NaCl, KCl, LiCl, NaI, NaNO3 and Na2SO4) with different ionic strengths (IS = 10-3, 10-2 and 10-1) over dolomite {1014} cleavage surfaces. We show that all electrolytes tested enhance dolomite dissolution. Moreover, the morphology and density of etch pits are controlled by the presence of different ions in solution. The etch pit spreading rate and dolomite dissolution rate depend on both (1) the nature of the electrolyte and (2) the ionic strength. This is in agreement with recent experimental studies on calcite dissolution (Ruiz-Agudo et al., 2010). This study highlights the role of electrolytes in dolomite dissolution and points to a common behavior for carbonate minerals. Our results suggest that soluble salts may play a critical role in the weathering of carbonate rocks, both in the natural environment, as well as in stone buildings and statuary, where the amount of solutes in pore waters is significant and can vary depending on evaporation and condensation phenomena. References Higgins, S.R.; Hu, X. Self-limiting growth on dolomite: Experimental observations with in situ atomic force microscopy. Geochimica et Cosmochimica Acta, 2005, 69 (8), 2085-2094. Morse, J.W.; Arvidson, R.S. The dissolution kinetics of major sedimentary carbonate minerals. Earth-Science Reviews, 2002, 58, 51-84. Ruiz-Agudo, E.; Kowacz, M.; Putnis, C.V.; Putnis, A. The role of background electrolytes on the kinetics and mechanism of calcite dissolution. Geochimica et Cosmochimica Acta, 2010, 74, 1256-1267.

Transient Pressure Test Article (TPTA) 1.1 and 1.1A, volume 1

NASA Technical Reports Server (NTRS)

Rebells, Clarence A.

1988-01-01

This final test report presents the results obtained during the static hot firing and cold-gas high Q tests of the first Transient Pressure Test Article (TPTA) 1.1. The TPTA consisted of field test joints A and B, which were the original RSRM J-insulation configuration, with a metal capture feature. It also consisted of a flight configuration nozzle-to-case test joint (Joint D) with shorter vent slots. Fluorocarbon O-rings were used in all the test joints. The purpose of the TPTA tests is to evaluate and characterize the RSMR field and nozzle-to-case joints under the influence of ignition and strut loads during liftoff anf high Q. All objectives of the cold-gas high Q (TPTA 1.1A) test were met and all measurements were close to predicted values. During the static hot-firing test (TPTA 1.1), the motor was inadvertently plugged by the quench injector plug, making it a more severe test, although no strut loads were applied. The motor was depressurized after approximately 11 min using an auxiliary system, and no anomalies were noted. In the static hot-firing test, pressure was incident on the insulation and the test joint gaps were within the predicted range. During the static hot-firing test, no strut loads were applied because the loading system malfunctioned. For this test, all measurements were within range of similar tests performed without strut loads.

Assessment of current AASHTO LRFD methods for static pile capacity analysis in Rhode Island soils.

DOT National Transportation Integrated Search

2013-07-01

This report presents an assessment of current AASHTO LRFD methods for static pile capacity analysis in Rhode : Island soils. Current static capacity methods and associated resistance factors are based on pile load test data in sands : and clays. Some...