Understanding Drug Release Data through Thermodynamic Analysis

PubMed Central

Freire, Marjorie Caroline Liberato Cavalcanti; Alexandrino, Francisco; Marcelino, Henrique Rodrigues; Picciani, Paulo Henrique de Souza; Silva, Kattya Gyselle de Holanda e; Genre, Julieta; de Oliveira, Anselmo Gomes; do Egito, Eryvaldo Sócrates Tabosa

2017-01-01

Understanding the factors that can modify the drug release profile of a drug from a Drug-Delivery-System (DDS) is a mandatory step to determine the effectiveness of new therapies. The aim of this study was to assess the Amphotericin-B (AmB) kinetic release profiles from polymeric systems with different compositions and geometries and to correlate these profiles with the thermodynamic parameters through mathematical modeling. Film casting and electrospinning techniques were used to compare behavior of films and fibers, respectively. Release profiles from the DDSs were performed, and the mathematical modeling of the data was carried out. Activation energy, enthalpy, entropy and Gibbs free energy of the drug release process were determined. AmB release profiles showed that the relationship to overcome the enthalpic barrier was PVA-fiber > PVA-film > PLA-fiber > PLA-film. Drug release kinetics from the fibers and the films were better fitted on the Peppas–Sahlin and Higuchi models, respectively. The thermodynamic parameters corroborate these findings, revealing that the AmB release from the evaluated systems was an endothermic and non-spontaneous process. Thermodynamic parameters can be used to explain the drug kinetic release profiles. Such an approach is of utmost importance for DDS containing insoluble compounds, such as AmB, which is associated with an erratic bioavailability. PMID:28773009

Kinetic and theoretical studies of novel biodegradable thermo-sensitive xerogels based on PEG/PVP/silica for sustained release of enrofloxacin

NASA Astrophysics Data System (ADS)

Ebadi, Azra; Rafati, Amir Abbas; Bavafa, Sadeghali; Mohammadi, Masoumah

2017-12-01

This study involves the synthesis of a new silica-based colloidal hybrid system. In this new hybrid system, poly (ethylene glycol) (PEG) and thermo-sensitive amphiphilic biocompatible poly (vinyl pyrrolidone) (PVP) were used to create suitable storage for hydrophobic drugs. The possibility of using variable PVP/PEG molar ratios to modulate drug release rate from silica nanoparticles was a primary goal of the current research. In addition, an investigation of the drug release kinetic was conducted. To achieve this, silica nanoparticles were synthesized in poly (ethylene glycol) (PEG) and poly (vinyl pyrrolidone) (PVP) solution incorporated with enrofloxacin (EFX) (as a model hydrophobic drug), using a simple synthetic strategy of hybrid materials which avoided waste and multi-step processes. The impacts of PVP/PEG molar ratios, temperature, and pH of the release medium on release kinetic were investigated. The physicochemical properties of the drug-loaded composites were studied by Fourier transform infrared (FT-IR) spectra, scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In vitro drug release studies demonstrated that the drug release rate, which was evaluated by analyzing the experimental data with seven kinetic models in a primarily non-Fickian diffusion-controlled process, aligned well with both Ritger-Peppas and Sahlin-Peppas equations.

Swelling kinetics of spray-dried chitosan acetate assessed by magnetic resonance imaging and their relation to drug release kinetics of chitosan matrix tablets.

PubMed

Huanbutta, Kampanart; Sriamornsak, Pornsak; Limmatvapirat, Sontaya; Luangtana-anan, Manee; Yoshihashi, Yasuo; Yonemochi, Etsuo; Terada, Katsuhide; Nunthanid, Jurairat

2011-02-01

Magnetic resonance imaging (MRI) was used to assess in situ swelling behaviors of spray-dried chitosan acetate (CSA) in 0.1N HCl, pH 6.8 and pH 5.0 Tris-HCl buffers. The in vitro drug releases from CSA matrix tablets containing the model drugs, diclofenac sodium and theophylline were investigated in all media using USP-4 apparatus. The effect of chitosan molecular weight, especially in pH 6.8 Tris-HCl, was also studied. In 0.1N HCl, the drug release from the matrix tablets was the lowest in relation to the highest swelling of CSA. The swelling kinetics in Tris-HCl buffers are Fickian diffusion according to their best fit to Higuchi's model as well as the drug release kinetics in all the media. The high swelling rate (k(s)(')) was found to delay the drug release rate (k'). The linear relationship between the swelling and fractions of drug release in Tris-HCl buffers was observed, indicating an important role of the swelling on controlling the drug release mechanism. Additionally, CSA of 200 and 800 kDa chitosan did not swell in pH 6.8 Tris-HCl but disintegrated into fractions, and the drug release from the matrix tablets was the highest. Copyright © 2010 Elsevier B.V. All rights reserved.

The effect of excipients on the release kinetics of diclofenac sodium and papaverine hydrochloride from composed tablets.

PubMed

Kasperek, Regina; Trebacz, Hanna; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

For increased analgesic effect, new composed tablets containing diclofenac sodium (DIC) with an addition of papaverine hydrochloride (PAP) were prepared to investigate the mechanism of release of the active substances from tablets with different excipients in eight different formulations. To detect the possible interactions between active substances and excipients differential scanning calorimetry (DSC) was used. A shift of the melting point and enthalpy values of the physical mixtures of tablets components suggested a kind of interaction between components in certain formulations, however, the tabletting process was not disturbed in any of them. Kinetics of drug release from formulations was estimated by zero order, first order and Higuchi and Korsmeyer-Peppas models using results of dissolution of DIC and PAP from tablets. The study revealed that the mechanism of release of active substances was dependent on the excipients contained in tablets and the best fitted kinetics models were obtained for formulations with potentially prolonged release of DIC and PAP.

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

PubMed Central

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

2016-01-01

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

Kinetic Modeling of Slow Energy Release in Non-Ideal Carbon Rich Explosives

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

Vitello, P; Fried, L; Glaesemann, K

2006-06-20

We present here the first self-consistent kinetic based model for long time-scale energy release in detonation waves in the non-ideal explosive LX-17. Non-ideal, insensitive carbon rich explosives, such as those based on TATB, are believed to have significant late-time slow release in energy. One proposed source of this energy is diffusion-limited growth of carbon clusters. In this paper we consider the late-time energy release problem in detonation waves using the thermochemical code CHEETAH linked to a multidimensional ALE hydrodynamics model. The linked CHEETAH-ALE model dimensional treats slowly reacting chemical species using kinetic rate laws, with chemical equilibrium assumed for speciesmore » coupled via fast time-scale reactions. In the model presented here we include separate rate equations for the transformation of the un-reacted explosive to product gases and for the growth of a small particulate form of condensed graphite to a large particulate form. The small particulate graphite is assumed to be in chemical equilibrium with the gaseous species allowing for coupling between the instantaneous thermodynamic state and the production of graphite clusters. For the explosive burn rate a pressure dependent rate law was used. Low pressure freezing of the gas species mass fractions was also included to account for regions where the kinetic coupling rates become longer than the hydrodynamic time-scales. The model rate parameters were calibrated using cylinder and rate-stick experimental data. Excellent long time agreement and size effect results were achieved.« less

Desorption kinetics of hydrophobic organic chemicals from sediment to water: a review of data and models.

PubMed

Birdwell, Justin; Cook, Robert L; Thibodeaux, Louis J

2007-03-01

Resuspension of contaminated sediment can lead to the release of toxic compounds to surface waters where they are more bioavailable and mobile. Because the timeframe of particle resettling during such events is shorter than that needed to reach equilibrium, a kinetic approach is required for modeling the release process. Due to the current inability of common theoretical approaches to predict site-specific release rates, empirical algorithms incorporating the phenomenological assumption of biphasic, or fast and slow, release dominate the descriptions of nonpolar organic chemical release in the literature. Two first-order rate constants and one fraction are sufficient to characterize practically all of the data sets studied. These rate constants were compared to theoretical model parameters and functionalities, including chemical properties of the contaminants and physical properties of the sorbents, to determine if the trends incorporated into the hindered diffusion model are consistent with the parameters used in curve fitting. The results did not correspond to the parameter dependence of the hindered diffusion model. No trend in desorption rate constants, for either fast or slow release, was observed to be dependent on K(OC) or aqueous solubility for six and seven orders of magnitude, respectively. The same was observed for aqueous diffusivity and sediment fraction organic carbon. The distribution of kinetic rate constant values was approximately log-normal, ranging from 0.1 to 50 d(-1) for the fast release (average approximately 5 d(-1)) and 0.0001 to 0.1 d(-1) for the slow release (average approximately 0.03 d(-1)). The implications of these findings with regard to laboratory studies, theoretical desorption process mechanisms, and water quality modeling needs are presented and discussed.

Kinetics and Mechanisms of Chemical and Biological Agents Release from Biopolymeric Microcapsules.

PubMed

Vinceković, Marko; Jurić, Slaven; Đermić, Edyta; Topolovec-Pintarić, Snježana

2017-11-08

Kinetics and mechanisms of copper cations and Trichoderma viride spores release from uncoated and chitosan coated alginate microcapsules were investigated. The gelation of a fixed amount of sodium alginate at different concentrations of copper ion solutions resulted in distinct kinetics and release mechanisms. The increase in copper cation concentration promoted, but the presence of the chitosan layer on the microcapsule surface and the increase in microcapsule size reduced the rate of active agent release. Fitting to simple Korsmeyer-Peppas empirical model revealed that the underlying release mechanism (Fickian diffusion or a combination of the diffusion and erosion mechanisms) depends on the copper cation concentration and presence of T. viride spores. The investigation pointed out that the proper selection of formulation variables helps in designing microcapsules with the desirable release of copper ions and T. viride for plant protection and nutrition.

Spray-dried nanofibrillar cellulose microparticles for sustained drug release.

PubMed

Kolakovic, Ruzica; Laaksonen, Timo; Peltonen, Leena; Laukkanen, Antti; Hirvonen, Jouni

2012-07-01

Nanofibrillar cellulose (also referred to as cellulose nanofibers, nanocellulose, microfibrillated or nanofibrillated cellulose) has gained a lot of attention in recent years in different research areas including biomedical applications. In this study we have evaluated the applicability of nanofibrillar cellulose (NFC) as a material for the formation of matrix systems for sustained drug delivery. For that purpose, drug loaded NFC microparticles were produced by a spray drying method. The microparticles were characterized in terms of size and morphology, total drug loading, and physical state of the encapsulated drug. Drug release from the microparticles was assessed by dissolution tests, and suitable mathematical models were used to explain the drug releasing kinetics. The particles had spherical shapes with diameters of around 5 μm; the encapsulated drug was mainly in amorphous form. The controlled drug release was achieved. The drug releasing curves were fitted to a mathematical model describing the drug releasing kinetics from a spherical matrix. Different drugs had different release kinetics, which was a consequence of several factors, including different solubilities of the drugs in the chosen medium and different affinities of the drugs to the NFC. It can be concluded that NFC microparticles can sustain drug release by forming a tight fiber network and thus limit drug diffusion from the system. Copyright © 2012 Elsevier B.V. All rights reserved.

Intravascular Drug Release Kinetics Dictate Arterial Drug Deposition, Retention, and Distribution

PubMed Central

Balakrishnan, Brinda; Dooley, John F.; Kopia, Gregory; Edelman, Elazer R.

2007-01-01

Millions of patients worldwide have received drug-eluting stents to reduce their risk for in-stent restenosis. The efficacy and toxicity of these local therapeutics depend upon arterial drug deposition, distribution, and retention. To examine how administered dose and drug release kinetics control arterial drug uptake, a model was created using principles of computational fluid dynamics and transient drug diffusion-convection. The modeling predictions for drug elution were validated using empiric data from stented porcine coronary arteries. Inefficient, minimal arterial drug deposition was predicted when a bolus of drug was released and depleted within seconds. Month-long stent-based drug release efficiently delivered nearly continuous drug levels, but the slow rate of drug presentation limited arterial drug uptake. Uptake was only maximized when the rates of drug release and absorption matched, which occurred for hour-long drug release. Of the two possibly means for increasing the amount of drug on the stent, modulation of drug concentration potently impacts the magnitude of arterial drug deposition, while changes in coating drug mass affect duration of release. We demonstrate the importance of drug release kinetics and administered drug dose in governing arterial drug uptake and suggest novel drug delivery strategies for controlling spatio-temporal arterial drug distribution. PMID:17868948

Hydrophilic thermoplastic polyurethanes for the manufacturing of highly dosed oral sustained release matrices via hot melt extrusion and injection molding.

PubMed

Verstraete, G; Van Renterghem, J; Van Bockstal, P J; Kasmi, S; De Geest, B G; De Beer, T; Remon, J P; Vervaet, C

2016-06-15

Hydrophilic aliphatic thermoplastic polyurethane (Tecophilic™ grades) matrices for high drug loaded oral sustained release dosage forms were formulated via hot melt extrusion/injection molding (HME/IM). Drugs with different aqueous solubility (diprophylline, theophylline and acetaminophen) were processed and their influence on the release kinetics was investigated. Moreover, the effect of Tecophilic™ grade, HME/IM process temperature, extrusion speed, drug load, injection pressure and post-injection pressure on in vitro release kinetics was evaluated for all model drugs. (1)H NMR spectroscopy indicated that all grades have different soft segment/hard segment ratios, allowing different water uptake capacities and thus different release kinetics. Processing temperature of the different Tecophilic™ grades was successfully predicted by using SEC and rheology. Tecophilic™ grades SP60D60, SP93A100 and TG2000 had a lower processing temperature than other grades and were further evaluated for the production of IM tablets. During HME/IM drug loads up to 70% (w/w) were achieved. In addition, Raman mapping and (M)DSC results confirmed the homogenous distribution of mainly crystalline API in all polymer matrices. Besides, hydrophilic TPU based formulations allowed complete and sustained release kinetics without using release modifiers. As release kinetics were mainly affected by drug load and the length of the PEO soft segment, this polymer platform offers a versatile formulation strategy to adjust the release rate of drugs with different aqueous solubility. Copyright © 2016 Elsevier B.V. All rights reserved.

Rainfall-Induced Release of Fecal Coliforms and Other Manure Constituents: Comparison and Modeling▿

PubMed Central

Guber, A. K.; Shelton, D. R.; Pachepsky, Y. A.; Sadeghi, A. M.; Sikora, L. J.

2006-01-01

Modeling release of fecal coliforms is an important component of fate and transport simulations related to environmental water quality. Manure constituents other than fecal coliforms may serve as natural tracers of fecal contamination provided that their release from manure to runoff is similar to the fecal coliform release. The objectives of this work were to compare release of fecal coliforms (FC), chloride (Cl−), organic carbon (OC), and water-soluble phosphorus (P) from dissolving manure and to assess the performance of three models in describing the observed release. Bovine manure was applied on 0.5- by 0.3-m bare and vegetated subplots with 20% slope on sandy loam and clay loam soils. Concentrations of Cl−, FC, OC, and P were measured in runoff collected from troughs at the edges of the subplots at 5-min intervals during 1-h rainfall simulations. The one-parametric exponential model and two-parametric Vadas-Kleinman-Sharpley model and Bradford-Schijven model were fitted to the data. The Bradford-Schijven model had uncorrelated parameters, one of which was linearly related to the irrigation rate, and another parameter reflected the presence or the absence of vegetation. Kinetics of the FC release from manure was similar to the release kinetics of P and OC. The Bradford-Schijven model is recommended to simulate the release of manure constituents. PMID:17028232

Drug release and swelling kinetics of directly compressed glipizide sustained-release matrices: establishment of level A IVIVC.

PubMed

Sankalia, Jolly M; Sankalia, Mayur G; Mashru, Rajashree C

2008-07-02

The purpose of this study was to examine a level A in vitro-in vivo correlation (IVIVC) for glipizide hydrophilic sustained-release matrices, with an acceptable internal predictability, in the presence of a range of formulation/manufacturing changes. The effect of polymeric blends of ethylcellulose, microcrystalline cellulose, hydroxypropylmethylcellulose, xanthan gum, guar gum, Starch 1500, and lactose on in vitro release profiles was studied and fitted to various release kinetics models. Water uptake kinetics with scanning electron microscopy (SEM) was carried out to support the drug release mechanism. An IVIVC was established by comparing the pharmacokinetic parameters of optimized (M-24) and marketed (Glytop-2.5 SR) formulations after single oral dose studies on white albino rabbits. The matrix M-19 (xanthan:MCC PH301 at 70:40) and M-24 (xanthan:HPMC K4M:Starch 1500 at 70:25:15) showed the glipizide release within the predetermined constraints at all time points with Korsmeyer-Peppas' and zero-order release mechanism, respectively. Kopcha model revealed that the xanthan gum is the major excipient responsible for the diffusional release profile and was further supported by SEM and swelling studies. A significant level A IVIVC with acceptable limits of prediction errors (below 15%) enables the prediction of in vivo performance from their in vitro release profile. It was concluded that proper selection of rate-controlling polymers with release rate modifier excipients will determine overall release profile, duration and mechanism from directly compressed matrices.

Release kinetics of papaverine hydrochloride from tablets with different excipients.

PubMed

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release.

Release Kinetics of Papaverine Hydrochloride from Tablets with Different Excipients

PubMed Central

Kasperek, Regina; Polski, Andrzej; Zimmer, Łukasz; Poleszak, Ewa

2014-01-01

Abstract The influence of excipients on the disintegration times of tablets and the release of papaverine hydrochloride (PAP) from tablets were studied. Ten different formulations of tablets with PAP were prepared by direct powder compression. Different binders, disintegrants, fillers, and lubricants were used as excipients. The release of PAP was carried out in the paddle apparatus using 0.1 N HCl as a dissolution medium. The results of the disintegration times of tablets showed that six formulations can be classified as fast dissolving tablets (FDT). FDT formulations contained Avicel PH 101, Avicel PH 102, mannitol, (3-lactose, PVP K 10, gelatinized starch (CPharmGel), Prosolv Easy Tab, Prosolv SMCC 90, magnesium stearate, and the addition of disintegrants such as AcDiSol and Kollidon CL. Drug release kinetics were estimated by the zero- and first-order, Higuchi release rate, and Korsmeyer-Peppas models. Two formulations of the tablets containing PVP (K10) (10%), CPharmGel (10% and 25%), and Prosolv Easy Tab (44% and 60%) without the addition of a disintegrant were well-fitted to the kinetics models such as the Higuchi and zero-order, which are suitable for controlled- or sustained-release. PMID:25853076

Kinetic models for the release of the anticancer drug doxorubicin from biodegradable polylactide/metal oxide-based hybrids.

PubMed

Mhlanga, Nikiwe; Ray, Suprakas Sinha

2015-01-01

For decades, studies on drug-release kinetics have been an important topic in the field of drug delivery because they provide important insights into the mechanism of drug release from carriers. In this work, polylactide (PLA), doxorubicin (DOX), and metal oxide (MO) (titanium dioxide, magnetic iron oxide, and zinc oxide) spheres were synthesised using the solvent-evaporation technique and were tested for sustained drug release. The efficacy of a dosage system is determined by its ability to deliver the drug at a sustained rate, afford an increased plasma half-life, a minimum exposure of toxic drugs to healthy cells and a high drug pay load. Mathematical models were used to elucidate the release mechanism of the drug from the spheres. The release fitted a zero-order model with a correlation coefficient in the range of 0.9878-0.9891 and the release mechanism followed an anomalous release, meaning drug release was afforded through both diffusion and the dissolution of PLA. Therefore, PLA/DOX/MO released the same amount of drug per unit time. Consequently, the potential for PLA use as a carrier was ascertained. Copyright © 2014 Elsevier B.V. All rights reserved.

Neurobiological model of stimulated dopamine neurotransmission to interpret fast-scan cyclic voltammetry data.

PubMed

Harun, Rashed; Grassi, Christine M; Munoz, Miranda J; Torres, Gonzalo E; Wagner, Amy K

2015-03-02

Fast-scan cyclic voltammetry (FSCV) is an electrochemical method that can assess real-time in vivo dopamine (DA) concentration changes to study the kinetics of DA neurotransmission. Electrical stimulation of dopaminergic (DAergic) pathways can elicit FSCV DA responses that largely reflect a balance of DA release and reuptake. Interpretation of these evoked DA responses requires a framework to discern the contribution of DA release and reuptake. The current, widely implemented interpretive framework for doing so is the Michaelis-Menten (M-M) model, which is grounded on two assumptions- (1) DA release rate is constant during stimulation, and (2) DA reuptake occurs through dopamine transporters (DAT) in a manner consistent with M-M enzyme kinetics. Though the M-M model can simulate evoked DA responses that rise convexly, response types that predominate in the ventral striatum, the M-M model cannot simulate dorsal striatal responses that rise concavely. Based on current neurotransmission principles and experimental FSCV data, we developed a novel, quantitative, neurobiological framework to interpret DA responses that assumes DA release decreases exponentially during stimulation and continues post-stimulation at a diminishing rate. Our model also incorporates dynamic M-M kinetics to describe DA reuptake as a process of decreasing reuptake efficiency. We demonstrate that this quantitative, neurobiological model is an extension of the traditional M-M model that can simulate heterogeneous regional DA responses following manipulation of stimulation duration, frequency, and DA pharmacology. The proposed model can advance our interpretive framework for future in vivo FSCV studies examining regional DA kinetics and their alteration by disease and DA pharmacology. Copyright © 2015 Elsevier B.V. All rights reserved.

Controllable delivery of hydrophilic and hydrophobic drugs from electrospun poly(lactic-co-glycolic acid)/mesoporous silica nanoparticles composite mats.

PubMed

Song, Botao; Wu, Chengtie; Chang, Jiang

2012-11-01

Co-delivery of several drugs has been regarded as an alternative strategy for achieving enhanced therapeutic effect. In this study, a co-delivery system based on the electrospun poly(lactic-co-glycolic acid) (PLGA)/mesoporous silica nanoparticles (MSNs) composite mat was designed for the co-encapsulation and prolonged release of one hydrophilic and one hydrophobic drug simultaneously. MSNs were chosen to load the hydrophobic model drug fluorescein (FLU) and hydrophilic model drug rhodamine B (RHB), respectively (named as RHB-loaded MSNs and FLU-loaded MSNs). Two kinds of drug-loaded MSNs were incorporated into the polymer matrix to form a fibrous structure by blending electrospinning. The effect of the weight ratios for the two kinds of drug-loaded MSNs and the initial PLGA concentrations on the drug release kinetics were systematically investigated. The results showed that both model drugs RHB and FLU maintained sustained delivery with controllable release kinetics during the releasing period, and the release kinetics was closely dependent on the loading ratios of two drug-loaded MSNs and the initial PLGA concentrations in the composite mats. The results suggest that the co-drug delivery system may be used for wound dressing that requires the combined therapy of several kinds of drugs. Copyright © 2012 Wiley Periodicals, Inc.

Sustained Release of Green Tea Polyphenols from Liposomal Nanoparticles; Release Kinetics and Mathematical Modelling.

PubMed

Prakash Upputuri, Ravi Theaj; Azad Mandal, Abul Kalam

2017-01-01

Background: Green tea polyphenols (GTP) are known to have several health benefits. In spite of these benefits, its application as a therapeutic agent is limited due to some of its limitations such as stability, bioavailability, and biotransformation. To overcome these limitations, liposomal nanoparticles have been used as a carrier of the GTP. Objective: Encapsulation of GTP to the liposomal nanoparticles in order to achieve a sustained release of the GTP and to determine the drug release kinetics and the mechanism of the release. Materials and Methods: GTP encapsulated liposomal nanoparticles were prepared using phosphatidyl choline and cholesterol. The synthesized particles were characterized for their particle size and morphology. In vitro release studies were carried out, followed by drug release kinetics, and determining the mechanism of release. In vitro , antioxidant assay was determined following 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Results: Atomic force microscope (AFM) and high resolution scanning electron microscope (HR SEM) images showed spherical particles of the size of 64.5 and 252 nm. An encapsulation efficiency as high as 77.7% was observed with GTP concentration of 5 mg.mL -1 . In vitro release studies showed that the loading concentrations of GTP were independent to the cumulative percentage of the drug release. GTP release by varying the pH and temperature showed a direct correlation between the release parameter and the percentage of drug release. The higher the pH and temperature, the higher was the percentage of the drug release. The release data showed a good correlation with Zero order kinetics and the mechanism of the release being anomalous mode. Radical scavenging activity of the released GTP showed a potent scavenging activity. Conclusion: GTP encapsulated liposomal nanoparticles could be used as a delivery vehicle for achieving a sustained release.

A model for the evolution in water chemistry of an arsenic contaminated aquifer over the last 6000 years, Red River floodplain, Vietnam

NASA Astrophysics Data System (ADS)

Postma, Dieke; Pham, Thi Kim Trang; Sø, Helle Ugilt; Hoang, Van Hoan; , Mai Lan, Vi; Nguyen, Thi Thai; Larsen, Flemming; Pham, Hung Viet; Jakobsen, Rasmus

2016-12-01

Aquifers on the Red River flood plain with burial ages ranging from 500 to 6000 years show, with increasing age, the following changes in solute concentrations; a decrease in arsenic, increase in Fe(II) and decreases in both pH, Ca and bicarbonate. These changes were interpreted in terms of a reaction network comprising the kinetics of organic carbon degradation, the reduction kinetics of As containing Fe-oxides, the sorption of arsenic, the kinetics of siderite precipitation and dissolution, as well as of the dissolution of CaCO3. The arsenic released from the Fe-oxide is preferentially partitioned into the water phase, and partially sorbed, while the released Fe(II) is precipitated as siderite. The reaction network involved in arsenic mobilization was analyzed by 1-D reactive transport modeling. The results reveal complex interactions between the kinetics of organic matter degradation and the kinetics and thermodynamic energy released by Fe-oxide reduction. The energy released by Fe-oxide reduction is strongly pH dependent and both methanogenesis and carbonate precipitation and dissolution have important influences on the pH. Overall it is the rate of organic carbon degradation that determines the total electron flow. However, the kinetics of Fe-oxide reduction determines the distribution of this flow of electrons between methanogenesis, which is by far the main pathway, and Fe-oxide reduction. Modeling the groundwater arsenic content over a 6000 year period in a 20 m thick aquifer shows an increase in As during the first 1200 years where it reaches a maximum of about 600 μg/L. During this initial period the release of arsenic from Fe-oxides actually decreases but the adsorption of arsenic onto the sediment delays the build-up in the groundwater arsenic concentration. After 1200 years the groundwater arsenic content slowly decreases controlled both by desorption and continued further, but diminishing, release from Fe-oxide being reduced. After 6000 years the arsenic content has decreased to 33 μg/L. The modeling enables a quantitative description of how the aquifer properties, the reactivity of organic carbon and Fe-oxides, the number of sorption sites and the buffering mechanisms change over a 6000 year period and how the combined effect of these interacting processes controls the groundwater arsenic content.

A model for the evolution in water chemistry of an arsenic contaminated aquifer over the last 6000 years, Red River floodplain, Vietnam

PubMed Central

Trang, Pham Thi Kim; Sø, Helle Ugilt; Van Hoan, Hoang; Lan, Vi Mai; Thai, Nguyen Thi; Larsen, Flemming; Viet, Pham Hung; Jakobsen, Rasmus

2016-01-01

Aquifers on the Red River flood plain with burial ages ranging from 500 to 6000 years show, with increasing age, the following changes in solute concentrations; a decrease in arsenic, increase in Fe(II) and decreases in both pH, Ca and bicarbonate. These changes were interpreted in terms of a reaction network comprising the kinetics of organic carbon degradation, the reduction kinetics of As containing Fe-oxides, the sorption of arsenic, the kinetics of siderite precipitation and dissolution, as well as of the dissolution of CaCO3. The arsenic released from the Fe-oxide is preferentially partitioned into the water phase, and partially sorbed, while the released Fe(II) is precipitated as siderite. The reaction network involved in arsenic mobilization was analyzed by 1-D reactive transport modeling. The results reveal complex interactions between the kinetics of organic matter degradation and the kinetics and thermodynamic energy released by Fe-oxide reduction. The energy released by Fe-oxide reduction is strongly pH dependent and both methanogenesis and carbonate precipitation and dissolution have important influences on the pH. Overall it is the rate of organic carbon degradation that determines the total electron flow. However, the kinetics of Fe-oxide reduction determines the distribution of this flow of electrons between methanogenesis, which is by far the main pathway, and Fe-oxide reduction. Modeling the groundwater arsenic content over a 6000 year period in a 20 m thick aquifer shows an increase in As during the first 1200 years where it reaches a maximum of about 600 μg/L. During this initial period the release of arsenic from Fe-oxides actually decreases but the adsorption of arsenic onto the sediment delays the build-up in the groundwater arsenic concentration. After 1200 years the groundwater arsenic content slowly decreases controlled both by desorption and continued further, but diminishing, release from Fe-oxide being reduced. After 6000 years the arsenic content has decreased to 33 μg/L. The modeling enables a quantitative description of how the aquifer properties, the reactivity of organic carbon and Fe-oxides, the number of sorption sites and the buffering mechanisms change over a 6000 year period and how the combined effect of these interacting processes controls the groundwater arsenic content. PMID:27867210

Chemical Kinetics of the TPS and Base Bleeding During Flight Test

NASA Technical Reports Server (NTRS)

Osipov, Viatcheslav; Ponizhovskaya, Ekaterina; Hafiychuck, Halyna; Luchinsky, Dmitry; Smelyanskiy, Vadim; Dagostino, Mark; Canabal, Francisco; Mobley, Brandon L.

2012-01-01

The present research deals with thermal degradation of polyurethane foam (PUF) during flight test. Model of thermal decomposition was developed that accounts for polyurethane kinetics parameters extracted from thermogravimetric analyses and radial heat losses to the surrounding environment. The model predicts mass loss of foam, the temperature and kinetic of release of the exhaust gases and char as function of heat and radiation loads. When PUF is heated, urethane bond break into polyol and isocyanate. In the first stage, isocyanate pyrolyses and oxidizes. As a result, the thermo-char and oil droplets (yellow smoke) are released. In the second decomposition stage, pyrolysis and oxidization of liquid polyol occur. Next, the kinetics of chemical compound release and the information about the reactions occurring in the base area are coupled to the CFD simulations of the base flow in a single first stage motor vertically stacked vehicle configuration. The CFD simulations are performed to estimate the contribution of the hot out-gassing, chemical reactions, and char oxidation to the temperature rise of the base flow. The results of simulations are compared with the flight test data.

Modulation of drug release kinetics of shellac-based matrix tablets by in-situ polymerization through annealing process.

PubMed

Limmatvapirat, Sontaya; Limmatvapirat, Chutima; Puttipipatkhachorn, Satit; Nunthanid, Jurairat; Luangtana-anan, Manee; Sriamornsak, Pornsak

2008-08-01

A new oral-controlled release matrix tablet based on shellac polymer was designed and developed, using metronidazole (MZ) as a model drug. The shellac-based matrix tablets were prepared by wet granulation using different amounts of shellac and lactose. The effect of annealing temperature and pH of medium on drug release from matrix tablets was investigated. The increased amount of shellac and increased annealing temperature significantly affected the physical properties (i.e., tablet hardness and tablet disintegration) and MZ release from the matrix tablets. The in-situ polymerization played a major role on the changes in shellac properties during annealing process. Though the shellac did not dissolve in acid medium, the MZ release in 0.1N HCl was faster than in pH 7.3 buffer, resulting from a higher solubility of MZ in acid medium. The modulation of MZ release kinetics from shellac-based matrix tablets could be accomplished by varying the amount of shellac or annealing temperature. The release kinetics was shifted from relaxation-controlled release to diffusion-controlled release when the amount of shellac or the annealing temperature was increased.

Influence of organic acids on kinetic release of chromium in soil contaminated with leather factory waste in the presence of some adsorbents.

PubMed

Taghipour, Marzieh; Jalali, Mohsen

2016-07-01

In this study, batch experiments were conducted to investigate the effects of nanoparticles (NPs) (MgO, ZnO, TiO2) and clay minerals (bentonite, zeolite) on the release of chromium (Cr) from leather factory waste (LFW) and LFW treated soil using organic acids. Chromium release from all treatments was studied in the presence of citric acid, oxalic acid and CaCl2 solutions. The results showed that, in all treatments, organic acids released more Cr than inorganic salt (CaCl2). The release of Cr by citric acid was higher than that by oxalic acid. In LFW treated soil and LFW, the release of Cr from the all treatments with NPs was less than that from the clay mineral treatments. On the other hand, in the presence of organic acids, Cr release by NPs and clay minerals decreased. Two kinetic models including pseudo-first- and pseudo-second-order model were tested to describe the time dependent Cr release data. Among the kinetic models used, the pseudo-second-order model generally gave the best fits to experimental data. Before and after release experiments, Cr in LFW, treated LFW, control soil and LFW treated soils were fractionated. In all treatments, the greatest amounts of Cr were found in the residual fraction (RES). The organic acids were effective in reducing the exchangeable (EXC), bound to organic matter (OM) and bound to carbonate (CAR) fractions of Cr in all treatments, whereas, after release of Cr from treated soils, Cr remained mainly in the RES fraction. The application of NPs and clay minerals in soil led to a significant transformation of Cr from mobile fractions to the RES fraction. Therefore, organic ligands played a dominant role in mobility and bioavailability of Cr and the removal of Cr by adsorbents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Graft copolymers of ethyl methacrylate on waxy maize starch derivatives as novel excipients for matrix tablets: drug release and fronts movement kinetics.

PubMed

Marinich, J A; Ferrero, C; Jiménez-Castellanos, M R

2012-04-01

A previous paper deals with the physicochemical and technological characterization of novel graft copolymers of ethyl methacrylate (EMA) on waxy maize starch (MS) and hydroxypropylstarch (MHS). The results obtained suggested the potential application of these copolymers as excipients for compressed non-disintegrating matrix tablets. Therefore, the purpose of the present study was to investigate the mechanism governing drug release from matrix systems prepared with the new copolymers and anhydrous theophylline or diltiazem HCl as model drugs with different solubility. The influence of the carbohydrate nature, drying procedure and initial pore network on drug release kinetics was also evaluated. Drug release experiments were performed from free tablets. Radial drug release and fronts movement kinetics were also analysed, and several mathematical models were employed to ascertain the drug release mechanisms. The drug release markedly depends on the drug solubility and the carbohydrate nature but is practically not affected by the drying process and the initial matrix porosity. A faster drug release is observed for matrices containing diltiazem HCl compared with those containing anhydrous theophylline, in accordance with the higher drug solubility and the higher friability of diltiazem matrices. In fact, although diffusion is the prevailing drug release mechanism for all matrices, the erosion mechanism seems to have some contribution in several formulations containing diltiazem. A reduction in the surface exposed to the dissolution medium (radial release studies) leads to a decrease in the drug release rate, but the release mechanism is not essentially modified. The nearly constant erosion front movement confirms the behaviour of these systems as inert matrices where the drugs are released mainly by diffusion through the porous structure. Copyright © 2011 Elsevier B.V. All rights reserved.

Release behavior and kinetic evaluation of berberine hydrochloride from ethyl cellulose/chitosan microspheres

NASA Astrophysics Data System (ADS)

Zhou, Hui-Yun; Cao, Pei-Pei; Zhao, Jie; Wang, Zhi-Ying; Li, Jun-Bo; Zhang, Fa-Liang

2014-12-01

Novel ethyl cellulose/chitosan microspheres (ECCMs) were prepared by the method of w/o/w emulsion and solvent evaporation. The microspheres were spherical, adhesive, and aggregated loosely with a size not bigger than 5 μm. The drug loading efficiency of berberine hydrochloride (BH) loaded in microspheres were affected by chitosan (CS) concentration, EC concentration and the volume ratio of V(CS)/ V(EC). ECCMs prepared had sustained release efficiency on BH which was changed with different preparation parameters. In addition, the pH value of release media had obvious effect on the release character of ECCMs. The release rate of BH from sample B was only a little more than 30% in diluted hydrochloric acid (dHCl) and that was almost 90% in PBS during 24 h. Furthermore, the drug release data were fitted to different kinetic models to analyze the release kinetics and the mechanism from the microspheres. The released results of BH indicated that ECCMs exhibited non-Fickian diffusion mechanism in dHCl and diffusion-controlled drug release based on Fickian diffusion in PBS. So the ECCMs might be an ideal sustained release system especially in dHCl and the drug release was governed by both diffusion of the drug and dissolution of the polymeric network.

Active food packaging based on molecularly imprinted polymers: study of the release kinetics of ferulic acid.

PubMed

Otero-Pazos, Pablo; Rodríguez-Bernaldo de Quirós, Ana; Sendón, Raquel; Benito-Peña, Elena; González-Vallejo, Victoria; Moreno-Bondi, M Cruz; Angulo, Immaculada; Paseiro-Losada, Perfecto

2014-11-19

A novel active packaging based on molecularly imprinted polymer (MIP) was developed for the controlled release of ferulic acid. The release kinetics of ferulic acid from the active system to food simulants (10, 20, and 50% ethanol (v/v), 3% acetic acid (w/v), and vegetable oil), substitutes (95% ethanol (v/v) and isooctane), and real food samples at different temperatures were studied. The key parameters of the diffusion process were calculated by using a mathematical modeling based on Fick's second law. The ferulic acid release was affected by the temperature as well as the percentage of ethanol of the simulant. The fastest release occurred in 95% ethanol (v/v) at 20 °C. The diffusion coefficients (D) obtained ranged between 1.8 × 10(-11) and 4.2 × 10(-9) cm(2)/s. A very good correlation between experimental and estimated data was obtained, and consequently the model could be used to predict the release of ferulic acid into food simulants and real food samples.

Influence of ionic complexation on release rate profiles from multiple water-in-oil-in-water (W/O/W) emulsions.

PubMed

Bonnet, Marie; Cansell, Maud; Placin, Frédéric; David-Briand, Elisabeth; Anton, Marc; Leal-Calderon, Fernando

2010-07-14

Water-in-oil-in-water (W/O/W) double emulsions were prepared, and the kinetics of release of magnesium ions from the internal to the external water phase was followed. Different chelating agents (phosvitin and gluconate) were used to bind magnesium within the prospect of improving the ion retention in the internal aqueous droplets. Magnesium release was monitored for 1 month of storage, for each formulation, with and without chelation, at two storage temperatures (4 and 25 degrees C). Leakage occurred without film rupturing (coalescence) and was mainly due to entropically driven diffusion/permeation phenomena. The experimental results revealed a clear correlation between the effectiveness of chelating agents to delay the delivery and their binding capacity characterized by the equilibrium affinity constant. The kinetic data (percent released versus time curves) were interpreted within the framework of a kinetic model based on diffusion and taking into account magnesium chelation.

Cholesterol Alters the Dynamics of Release in Protein Independent Cell Models for Exocytosis

NASA Astrophysics Data System (ADS)

Najafinobar, Neda; Mellander, Lisa J.; Kurczy, Michael E.; Dunevall, Johan; Angerer, Tina B.; Fletcher, John S.; Cans, Ann-Sofie

2016-09-01

Neurons communicate via an essential process called exocytosis. Cholesterol, an abundant lipid in both secretory vesicles and cell plasma membrane can affect this process. In this study, amperometric recordings of vesicular dopamine release from two different artificial cell models created from a giant unilamellar liposome and a bleb cell plasma membrane, show that with higher membrane cholesterol the kinetics for vesicular release are decelerated in a concentration dependent manner. This reduction in exocytotic speed was consistent for two observed modes of exocytosis, full and partial release. Partial release events, which only occurred in the bleb cell model due to the higher tension in the system, exhibited amperometric spikes with three distinct shapes. In addition to the classic transient, some spikes displayed a current ramp or plateau following the maximum peak current. These post spike features represent neurotransmitter release from a dilated pore before constriction and show that enhancing membrane rigidity via cholesterol adds resistance to a dilated pore to re-close. This implies that the cholesterol dependent biophysical properties of the membrane directly affect the exocytosis kinetics and that membrane tension along with membrane rigidity can influence the fusion pore dynamics and stabilization which is central to regulation of neurochemical release.

A kinetic model for chemical neurotransmission

NASA Astrophysics Data System (ADS)

Ramirez-Santiago, Guillermo; Martinez-Valencia, Alejandro; Fernandez de Miguel, Francisco

Recent experimental observations in presynaptic terminals at the neuromuscular junction indicate that there are stereotyped patterns of cooperativeness in the fusion of adjacent vesicles. That is, a vesicle in hemifusion process appears on the side of a fused vesicle and which is followed by another vesicle in a priming state while the next one is in a docking state. In this talk we present a kinetic model for this morphological pattern in which each vesicle state previous to the exocytosis is represented by a kinetic state. This chain states kinetic model can be analyzed by means of a Master equation whose solution is simulated with the stochastic Gillespie algorithm. With this approach we have reproduced the responses to the basal release in the absence of stimulation evoked by the electrical activity and the phenomena of facilitation and depression of neuromuscular synapses. This model offers new perspectives to understand the underlying phenomena in chemical neurotransmission based on molecular interactions that result in the cooperativity between vesicles during neurotransmitter release. DGAPA Grants IN118410 and IN200914 and Conacyt Grant 130031.

Optimization of propranolol HCl release kinetics from press coated sustained release tablets.

PubMed

Ali, Adel Ahmed; Ali, Ahmed Mahmoud

2013-01-01

Press-coated sustained release tablets offer a valuable, cheap and easy manufacture alternative to the highly expensive, multi-step manufacture and filling of coated beads. In this study, propranolol HCl press-coated tablets were prepared using hydroxylpropylmethylcellulose (HPMC) as tablet coating material together with carbopol 971P and compressol as release modifiers. The prepared formulations were optimized for zero-order release using artificial neural network program (INForm, Intelligensys Ltd, North Yorkshire, UK). Typical zero-order release kinetics with extended release profile for more than 12 h was obtained. The most important variables considered by the program in optimizing formulations were type and proportion of polymer mixture in the coat layer and distribution ratio of drug between core and coat. The key elements found were; incorporation of 31-38 % of the drug in the coat, fixing the amount of polymer in coat to be not less than 50 % of coat layer. Optimum zero-order release kinetics (linear regression r2 = 0.997 and Peppas model n value > 0.80) were obtained when 2.5-10 % carbopol and 25-42.5% compressol were incorporated into the 50 % HPMC coat layer.

Controlled release of functional proteins through designer self-assembling peptide nanofiber hydrogel scaffold

PubMed Central

Koutsopoulos, Sotirios; Unsworth, Larry D.; Nagai, Yusuke; Zhang, Shuguang

2009-01-01

The release kinetics for a variety of proteins of a wide range of molecular mass, hydrodynamic radii, and isoelectric points through a nanofiber hydrogel scaffold consisting of designer self-assembling peptides were studied by using single-molecule fluorescence correlation spectroscopy (FCS). In contrast to classical diffusion experiments, the single-molecule approach allowed for the direct determination of diffusion coefficients for lysozyme, trypsin inhibitor, BSA, and IgG both inside the hydrogel and after being released into the solution. The results of the FCS analyses and the calculated pristine in-gel diffusion coefficients were compared with the values obtained from the Stokes–Einstein equation, Fickian diffusion models, and the literature. The release kinetics suggested that protein diffusion through nanofiber hydrogels depended primarily on the size of the protein. Protein diffusivities decreased, with increasing hydrogel nanofiber density providing a means of controlling the release kinetics. Secondary and tertiary structure analyses and biological assays of the released proteins showed that encapsulation and release did not affect the protein conformation and functionality. Our results show that this biocompatible and injectable designer self-assembling peptide hydrogel system may be useful as a carrier for therapeutic proteins for sustained release applications. PMID:19273853

Development and optimization of buspirone oral osmotic pump tablet

PubMed Central

Derakhshandeh, K.; berenji, M. Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump–based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance. PMID:25657794

Development and optimization of buspirone oral osmotic pump tablet.

PubMed

Derakhshandeh, K; Berenji, M Ghasemnejad

2014-01-01

The aim of the current study was to design a porous osmotic pump-based drug delivery system for controlling the release of buspirone from the delivery system. The osmotic pump was successfully developed using symmetric membrane coating. The core of the tablets was prepared by direct compression technique and coated using dip-coating technique. Drug release from the osmotic system was studied using USP paddle type apparatus. The effect of various processing variables such as the amount of osmotic agent, the amount of swellable polymer, concentration of the core former, concentration of the plasticizer, membrane thickness, quantum of orifice on drug release from osmotic pump were evaluated. Different kinetic models (zero order, first order and Higuchi model) were applied to drug release data in order to establish the kinetics of drug release. It was found that the drug release was mostly affected by the amount of NaCl as osmotic agent, the swellable polymer; hydroxy propyl methyl cellulose (HPMC), the amount of PEG-400 and cellulose acetate in the coating solution and thickness of the semipermeable membrane. The optimized formulation released buspirone independent of pH and orifice quantum at the osmogen amount of 42%, hydrophilic polymer of 13% and pore size of 0.8 mm on the tablet surface. The drug release of osmotic formulation during 24 h showed zero order kinetics and could be suggested that this formulation as a once-daily regimen improves pharmacokinetic parameters of the drug and enhances patient compliance.

Insights into accelerated liposomal release of topotecan in plasma monitored by a non-invasive fluorescence spectroscopic method

PubMed Central

Fugit, Kyle D.; Jyoti, Amar; Upreti, Meenakshi; Anderson, Bradley D.

2014-01-01

A non-invasive fluorescence method was developed to monitor liposomal release kinetics of the anticancer agent topotecan (TPT) in physiological fluids and subsequently used to explore the cause of accelerated release in plasma. Analyses of fluorescence excitation spectra confirmed that unencapsulated TPT exhibits a red shift in its spectrum as pH is increased. This property was used to monitor TPT release from actively loaded liposomal formulations having a low intravesicular pH. Mathematical release models were developed to extract reliable rate constants for TPT release in aqueous solutions monitored by fluorescence and release kinetics obtained by HPLC. Using the fluorescence method, accelerated TPT release was observed in plasma as previously reported in the literature. Simulations to estimate the intravesicular pH were conducted to demonstrate that accelerated release correlated with alterations in the low intravesicular pH. This was attributed to the presence of ammonia in plasma samples rather than proteins and other plasma components generally believed to alter release kinetics in physiological samples. These findings shed light on the critical role that ammonia may play in contributing to the preclinical/clinical variability and performance seen with actively-loaded liposomal formulations of TPT and other weakly-basic anticancer agents. PMID:25456833

Novel kinetic model of the removal of divalent heavy metal ions from aqueous solutions by natural clinoptilolite.

PubMed

Jovanovic, Mina; Rajic, Nevenka; Obradovic, Bojana

2012-09-30

Removal of heavy metal ions from aqueous solutions using zeolites is widely described by pseudo-second order kinetics although this model may not be valid under all conditions. In this work, we have extended approaches used for derivation of this model in order to develop a novel kinetic model that is related to the ion exchange mechanism underlying sorption of metal ions in zeolites. The novel model assumed two reversible steps, i.e. release of sodium ions from the zeolite lattice followed by bonding of the metal ion. The model was applied to experimental results of Cu(II) sorption by natural clinoptilolite-rich zeolitic tuff at different initial concentrations and temperatures and then validated by predictions of ion exchange kinetics of other divalent heavy metal ions (i.e. Mn(II), Zn(II) and Pb(II)). Model predictions were in excellent agreements with experimental data for all investigated systems. In regard to the proposed mechanism, modeling results implied that the sodium ion release rate was constant for all investigated metals while the overall rate was mainly determined by the rate of heavy metal ion bonding to the lattice. In addition, prediction capabilities of the novel model were demonstrated requiring one experimentally determined parameter, only. Copyright © 2012 Elsevier B.V. All rights reserved.

Transient release kinetics of rod bipolar cells revealed by capacitance measurement of exocytosis from axon terminals in rat retinal slices.

PubMed

Oltedal, Leif; Hartveit, Espen

2010-05-01

Presynaptic transmitter release has mostly been studied through measurements of postsynaptic responses, but a few synapses offer direct access to the presynaptic terminal, thereby allowing capacitance measurements of exocytosis. For mammalian rod bipolar cells, synaptic transmission has been investigated in great detail by recording postsynaptic currents in AII amacrine cells. Presynaptic measurements of the dynamics of vesicular cycling have so far been limited to isolated rod bipolar cells in dissociated preparations. Here, we first used computer simulations of compartmental models of morphologically reconstructed rod bipolar cells to adapt the 'Sine + DC' technique for capacitance measurements of exocytosis at axon terminals of intact rod bipolar cells in retinal slices. In subsequent physiological recordings, voltage pulses that triggered presynaptic Ca(2+) influx evoked capacitance increases that were proportional to the pulse duration. With pulse durations 100 ms, the increase saturated at 10 fF, corresponding to the size of a readily releasable pool of vesicles. Pulse durations 400 ms evoked additional capacitance increases, probably reflecting recruitment from additional pools of vesicles. By using Ca(2+) tail current stimuli, we separated Ca(2+) influx from Ca(2+) channel activation kinetics, allowing us to estimate the intrinsic release kinetics of the readily releasable pool, yielding a time constant of 1.1 ms and a maximum release rate of 2-3 vesicles (release site)(1) ms(1). Following exocytosis, we observed endocytosis with time constants ranging from 0.7 to 17 s. Under physiological conditions, it is likely that release will be transient, with the kinetics limited by the activation kinetics of the voltage-gated Ca(2+) channels.

Model studies on the release of aroma compounds from structured and nonstructured oil systems using proton-transfer reaction mass spectrometry.

PubMed

Landy, Pascale; Pollien, Philippe; Rytz, Andreas; Leser, Martin E; Sagalowicz, Laurent; Blank, Imre; Spadone, Jean-Claude

2007-03-07

Relative retention, volatility, and temporal release of volatile compounds taken from aldehyde, ester, and alcohol chemical classes were studied at 70 degrees C in model systems using equilibrium static headspace analysis and real time dynamic headspace analysis. These systems were medium-chain triglycerides (MCT), sunflower oil, and two structured systems, i.e., water-in-oil emulsion and L2 phase (water-in-oil microemulsion). Hydrophilic domains of the emulsion type media retained specifically the hydrophilic compounds and alcohols. Four kinetic parameters characterizing the concentration- and time-dependent releases were extracted from the aroma release curves. Most of the kinetic parameter values were higher in structured systems than in oils particularly when using MCT. The oil nature was found to better control the dynamic release profiles than the system structures. The release parameters were well-related (i) to the volatile hydrophobicity as a function of the oil used and (ii) to the retention data in the specific case of the L2 phase due to a specific release behavior of alcohols.

Design and in vivo evaluation of carvedilol buccal mucoadhesive patches.

PubMed

Thimmasetty, J; Pandey, G S; Babu, P R Sathesh

2008-07-01

The buccal region offers an attractive route of administration for systemic drug delivery. Carvedilol (dose, 3.125-25 mg) is beta-adrenergic antagonist. Its oral bioavailability is 25-35% because of first pass metabolism. Buccal absorption studies of a carvedilol solution in human volunteers showed 32.86% drug absorption. FTIR and UV spectroscopic methods revealed that there was no interaction between carvedilol and polymers. Carvedilol patches were prepared using HPMC, carbopol 934, eudragit RS 100, and ethylcellulose. The patches were evaluated for their thickness uniformity, folding endurance, weight uniformity, content uniformity, swelling behaviour, tensile strength, and surface pH. In vitro release studies were conducted for carvedilol-loaded patches in phosphate buffer (pH, 6.6) solution. Patches exhibited drug release in the range of 86.26 to 98.32% in 90 min. Data of in vitro release from patches were fit to different equations and kinetic models to explain release profiles. Kinetic models used were zero and first-order equations, Hixon-Crowell, Higuchi, and Korsmeyer-Peppas models. In vivo drug release studies in rabbits showed 90.85% of drug release from HPMC-carbopol patch while it was 74.63 to 88.02% within 90 min in human volunteers. Good correlation among in vitro release and in vivo release of carvedilol was observed.

A Markov State-based Quantitative Kinetic Model of Sodium Release from the Dopamine Transporter

NASA Astrophysics Data System (ADS)

Razavi, Asghar M.; Khelashvili, George; Weinstein, Harel

2017-01-01

The dopamine transporter (DAT) belongs to the neurotransmitter:sodium symporter (NSS) family of membrane proteins that are responsible for reuptake of neurotransmitters from the synaptic cleft to terminate a neuronal signal and enable subsequent neurotransmitter release from the presynaptic neuron. The release of one sodium ion from the crystallographically determined sodium binding site Na2 had been identified as an initial step in the transport cycle which prepares the transporter for substrate translocation by stabilizing an inward-open conformation. We have constructed Markov State Models (MSMs) from extensive molecular dynamics simulations of human DAT (hDAT) to explore the mechanism of this sodium release. Our results quantify the release process triggered by hydration of the Na2 site that occurs concomitantly with a conformational transition from an outward-facing to an inward-facing state of the transporter. The kinetics of the release process are computed from the MSM, and transition path theory is used to identify the most probable sodium release pathways. An intermediate state is discovered on the sodium release pathway, and the results reveal the importance of various modes of interaction of the N-terminus of hDAT in controlling the pathways of release.

Influence of graphene-oxide nanosheets impregnation on properties of sterculia gum-polyacrylamide hydrogel formed by radiation induced polymerization.

PubMed

Singh, Baljit; Singh, Baldev

2017-06-01

Present work is an attempt, to explore the potential of graphene oxide nanoplates impregnation, on the mechanical and drug delivery properties of sterculia gum-polyacrylamide composite hydrogel formed by radiation induced polymerization. These polymers were characterized by SEM, cryo-SEM, AFM, FTIR's, 13 C NMR and swelling studies. Release profile of an anticancer drug 'gemcitabine' was studied to determine the drug release mechanism and best fit kinetic model. Furthermore, some important biomedical properties of the polymers such as blood compatibility, mucoadhesion, antioxidant properties and gel strength were also studied. Impregnation of GO into sterculia gum-poly(AAm) hydrogels decreased the swelling of hydrogels but improved the mechanical, drug loading and drug release properties of the hydrogels. Release of gemcitabine from drug loaded hydrogels occurred through non-Fickian diffusion mechanism and release profile was best fitted in first order kinetic model. These hydrogels have been found as haemocompatible, mucoadhesive, and antioxidant in nature. Copyright © 2017 Elsevier B.V. All rights reserved.

The effect of charge on the release kinetics from polysaccharide-nanoclay composites

NASA Astrophysics Data System (ADS)

Del Buffa, Stefano; Grifoni, Emanuele; Ridi, Francesca; Baglioni, Piero

2015-03-01

The objective of this study was to integrate inorganic halloysite nanotubes (HNT) with chitosan and hyaluronic acid to obtain hybrid nanocomposites with opposing charges and to investigate their potential in the controlled release of drug model probes. Two oppositely charged polysaccharides, chitosan and hyaluronic acid, were selected for their biocompatibility and their importance in biomedical applications. The high surface area and the hollow nanometric-sized lumen of HNT allowed for the efficient loading of rhodamine 110 and carboxyfluorescein, used as models for oppositely charged drugs. In the case of chitosan, the preparation of the nanocomposite was carried out exploiting the electrostatic interaction between the polymer and HNT in water, while with hyaluronic acid, a covalent functionalization strategy was employed to couple the polymer with the clay. Nanocomposites were characterized with thermal, microscopic, and spectroscopic techniques, and the release kinetics of the model compounds was assessed by fluorescence measurements. The release curves were fitted with a model able to account for the desorption process from the external and the internal halloysite surfaces. The results show that both polymeric coatings alter the release of the probes, indicating a key role of both charge and coating composition on the initial and final amount of released dye, as well as on the rate of the desorption process.

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine.

PubMed

Tanaka, Nobuyuki; Imai, Keiji; Okimoto, Kazuto; Ueda, Satoshi; Tokunaga, Yuji; Ohike, Atsuo; Ibuki, Rinta; Higaki, Kazutaka; Kimura, Toshikiro

2005-11-28

The goal of this study is to develop a novel sustained-release (SR) system for poorly water-soluble drugs by applying solid dispersion (SD) technique for improving the solubility. The developed SR system, disintegration-controlled matrix tablet (DCMT), consists of hydrogenated soybean oil (HSO) as wax and SD granules containing low-substituted hydroxypropylcellulose (L-HPC) as a disintegrant. In this study, nilvadipine (NiD) was chosen as a model compound. Sustained-release profiles of NiD from DCMT were identically controlled in several dissolution mediums in spite of varying pH and agitation speed. The release of NiD from DCMT was sustained more effectively by increasing the amount of wax or by decreasing the amount of disintegrant, and supersaturation of NiD was achieved without any re-crystallization in dissolution medium. The release rate of NiD from DCMT was controlled by the disintegration rate of tablet. The release profile of NiD was described by the Hixson-Crowell's model better than zero-order kinetics, first-order kinetics and Higuchi's model, which supports that the release of NiD from DCMT is regulated by the disintegration of the tablet. From this study, it was clarified that DCMT was one of the promising SR systems applying SD for the poorly water-soluble drugs.

Escherichia coli Survival in, and Release from, White-Tailed Deer Feces

PubMed Central

Fry, Jessica; Ives, Rebecca L.; Rose, Joan B.

2014-01-01

White-tailed deer are an important reservoir for pathogens that can contribute a large portion of microbial pollution in fragmented agricultural and forest landscapes. The scarcity of experimental data on survival of microorganisms in and release from deer feces makes prediction of their fate and transport less reliable and development of efficient strategies for environment protection more difficult. The goal of this study was to estimate parameters for modeling Escherichia coli survival in and release from deer (Odocoileus virginianus) feces. Our objectives were as follows: (i) to measure survival of E. coli in deer pellets at different temperatures, (ii) to measure kinetics of E. coli release from deer pellets at different rainfall intensities, and (iii) to estimate parameters of models describing survival and release of microorganisms from deer feces. Laboratory experiments were conducted to study E. coli survival in deer pellets at three temperatures and to estimate parameters of Chick's exponential model with temperature correction based on the Arrhenius equation. Kinetics of E. coli release from deer pellets were measured at two rainfall intensities and used to derive the parameters of Bradford-Schijven model of bacterial release. The results showed that parameters of the survival and release models obtained for E. coli in this study substantially differed from those obtained by using other source materials, e.g., feces of domestic animals and manures. This emphasizes the necessity of comprehensive studies of survival of naturally occurring populations of microorganisms in and release from wildlife animal feces in order to achieve better predictions of microbial fate and transport in fragmented agricultural and forest landscapes. PMID:25480751

Pharmaceutical quality of "party pills" raises additional safety concerns in the use of illicit recreational drugs.

PubMed

Young, Simon A; Thrimawithana, Thilini R; Antia, Ushtana; Fredatovich, John D; Na, Yonky; Neale, Peter T; Roberts, Amy F; Zhou, Huanyi; Russell, Bruce

2013-06-14

To determine the content and release kinetics of 1-benzylpiperazine (BZP) and 1-(3-trifluoromethyl-phenyl)piperazine (TFMPP) from "party pill" formulations. From these data, the possible impact of pharmaceutical quality upon the safety of such illicit formulations may be inferred. The amount of BZP and TFMPP in party pill formulations was determined using a validated HPLC method. The in-vitro release kinetics of selected party pill brands were determined using a USP dissolution apparatus (75 rpm, 37.5 degrees Celsius). The release data were then fitted to a first order release model using PLOT software and the time taken to achieve 90% release reported. Many of the tested party pill brands contained amounts of BZP and TFMPP that varied considerably from that stated on the packaging; including considerable TFMPP content in some brands not labelled to contain this drug. Dissolution studies revealed that there was considerable variability in the release kinetics between brands; in one case 90% release required >30 minutes. Lack of quality control in party pill manufacture may have led to the toxic effects reported by users unaware of the true content and release of drug from pills. More stringent regulation in the manufacture and quality control of "new generation party pills" is essential to the harm reduction campaign.

Formulation and in-vitro evaluation of floating bilayer tablet of lisinopril maleate and metoprolol tartrate.

PubMed

Ijaz, Hira; Qureshi, Junaid; Danish, Zeeshan; Zaman, Muhammad; Abdel-Daim, Mohamed; Hanif, Muhammad; Waheed, Imran; Mohammad, Imran Shair

2015-11-01

The purpose of this study was to introduce the technology for the development of rate-controlled oral drug delivery system to overcome various physiological problems. Several approaches are being used for the purpose of increasing the gastric retentive time, including floating drug delivery system. Gastric floating lisinopril maleate and metoprolol tartrate bilayer tablets were formulated by direct compression method using the sodium starch glycolate, crosscarmellose sodium for IR layer. Eudragit L100, pectin, acacia as sustained release polymers in different ratios for SR metoprolol tartrate layer and sodium bicarbonate, citric acid as gas generating agents for the floating extended release layer. The floating bilayer tablets of lisinopril maleate and metoprolol tartrate were designed to overcome the various problems associated with conventional oral dosage form. Floating tablets were evaluated for floating lag time, drug contents and in-vitro dissolution profile and different kinetic release models were applied. It was clear that the different ratios of polymers affected the drug release and floating time. L2 and M4 showed good drug release profile and floating behavior. The linear regression and model fitting showed that all formulation followed Higuchi model of drug release model except M4 that followed zero order kinetic. From the study it is evident that a promising controlled release by floating bilyer tablets of lisinopril maleate and metoprolol tartrate can be developed successfully.

Transient state kinetic investigation of ferritin iron release

NASA Astrophysics Data System (ADS)

Ciasca, G.; Papi, M.; Chiarpotto, M.; Rodio, M.; Campi, G.; Rossi, C.; De Sole, P.; Bianconi, A.

2012-02-01

Increased iron concentration in tissues appears to be a factor in the genesis and development of inflammatory and degenerative diseases. By means of real-time small angle x-ray scattering measurements, we studied the kinetics of iron release from the ferritin inorganic core as a function of time and distance from the iron core centre. Accordingly, the iron release process follows a three step model: (i) a defect nucleation in the outer part of the mineral core, (ii) the diffusion of the reducing agent towards the inner part of the core, and (iii) the erosion of the core from the inner to the outer part.

Combined TGA-MS kinetic analysis of multistep processes. Thermal decomposition and ceramification of polysilazane and polysiloxane preceramic polymers.

PubMed

García-Garrido, C; Sánchez-Jiménez, P E; Pérez-Maqueda, L A; Perejón, A; Criado, José M

2016-10-26

The polymer-to-ceramic transformation kinetics of two widely employed ceramic precursors, 1,3,5,7-tetramethyl-1,3,5,7-tetravinylcyclotetrasiloxane (TTCS) and polyureamethylvinylsilazane (CERASET), have been investigated using coupled thermogravimetry and mass spectrometry (TG-MS), Raman, XRD and FTIR. The thermally induced decomposition of the pre-ceramic polymer is the critical step in the synthesis of polymer derived ceramics (PDCs) and accurate kinetic modeling is key to attaining a complete understanding of the underlying process and to attempt any behavior predictions. However, obtaining a precise kinetic description of processes of such complexity, consisting of several largely overlapping physico-chemical processes comprising the cleavage of the starting polymeric network and the release of organic moieties, is extremely difficult. Here, by using the evolved gases detected by MS as a guide it has been possible to determine the number of steps that compose the overall process, which was subsequently resolved using a semiempirical deconvolution method based on the Frasier-Suzuki function. Such a function is more appropriate that the more usual Gaussian or Lorentzian functions since it takes into account the intrinsic asymmetry of kinetic curves. Then, the kinetic parameters of each constituent step were independently determined using both model-free and model-fitting procedures, and it was found that the processes obey mostly diffusion models which can be attributed to the diffusion of the released gases through the solid matrix. The validity of the obtained kinetic parameters was tested not only by the successful reconstruction of the original experimental curves, but also by predicting the kinetic curves of the overall processes yielded by different thermal schedules and by a mixed TTCS-CERASET precursor.

Marine structure derived calcium phosphate-polymer biocomposites for local antibiotic delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L; Milthorpe, Bruce

2015-01-20

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery.

Marine Structure Derived Calcium Phosphate–Polymer Biocomposites for Local Antibiotic Delivery

PubMed Central

Macha, Innocent J.; Cazalbou, Sophie; Ben-Nissan, Besim; Harvey, Kate L.; Milthorpe, Bruce

2015-01-01

Hydrothermally converted coralline hydroxyapatite (HAp) particles loaded with medically active substances were used to develop polylactic acid (PLA) thin film composites for slow drug delivery systems. The effects of HAp particles within PLA matrix on the gentamicin (GM) release and release kinetics were studied. The gentamicin release kinetics seemed to follow Power law Korsmeyer Peppas model with mainly diffusional process with a number of different drug transport mechanisms. Statistical analysis shows very significant difference on the release of gentamicin between GM containing PLA (PLAGM) and GM containing HAp microspheres within PLA matrix (PLAHApGM) devices, which PLAHApGM displays lower release rates. The use of HAp particles improved drug stabilization and higher drug encapsulation efficiency of the carrier. HAp is also the source of Ca2+ for the regeneration and repair of diseased bone tissue. The release profiles, exhibited a steady state release rate with significant antimicrobial activity against Staphylococcus aureus (S. aureus) (SH1000) even at high concentration of bacteria. The devices also indicated significant ability to control the growth of bacterial even after four weeks of drug release. Clinical release profiles can be easily tuned from drug-HAp physicochemical interactions and degradation kinetics of polymer matrix. The developed systems could be applied to prevent microbial adhesion to medical implant surfaces and to treat infections mainly caused by S. aureus in surgery. PMID:25608725

The main beam correction term in kinetic energy release from metastable peaks.

PubMed

Petersen, Allan Christian

2017-12-01

The correction term for the precursor ion signal width in determination of kinetic energy release is reviewed, and the correction term is formally derived. The derived correction term differs from the traditionally applied term. An experimental finding substantiates the inaccuracy in the latter. The application of the "T-value" to study kinetic energy release is found preferable to kinetic energy release distributions when the metastable peaks are slim and simple Gaussians. For electronically predissociated systems, a "borderline zero" kinetic energy release can be directly interpreted in reaction dynamics with strong curvature in the reaction coordinate. Copyright © 2017 John Wiley & Sons, Ltd.

Phase Composition Control of Calcium Phosphate Nanoparticles for Tunable Drug Delivery Kinetics and Treatment of Osteomyelitis. Part 1: Preparation and Drug Release

PubMed Central

Uskoković, Vuk; Desai, Tejal A.

2012-01-01

Developed in this study is a multifunctional material for simultaneous osseoinduction and drug delivery, potentially applicable in the treatment of osteomyelitis. It is composed of agglomerates of nanoparticles of calcium phosphate (CAP) with different monophasic contents. The drug loading capacity and the release kinetics were investigated on two model drug compounds with different chemical structures, sizes and adsorption propensities: bovine serum albumin and fluorescein. Loading of CAP powders with small molecule drugs was achieved by physisorption and desiccation-induced agglomeration of nanoparticulate subunits into microscopic blocks. The material dissolution rate and the drug release rate depended on the nature of the CAP phase, decreasing from monocalcium phosphate to monetite to amorphous CAP and calcium pyrophosphate to hydroxyapatite. The sustained release of the two model drugs was shown to be directly relatable to the degradation rate of CAP carriers. It was demonstrated that the degradation rate of the carrier and the drug release kinetics could be made tunable within the time scale of 1–2 h for the most soluble CAP phase, monocalcium phosphate, to 1–2 years for the least soluble one, hydroxyapatite. From the standpoint of antibiotic therapy for osteomyelitis, typically lasting for six weeks, the most prospective CAP powder was amorphous CAP with its release time scale for a small organic molecule, the same category to which antibiotics belong, of 1 – 2 months under the conditions applied in our experiments. By combining these different CAP phases in various proportions, drug release profiles could be tailored to the therapeutic occasion. PMID:23115118

Kinetic coupling of phosphate release, force generation and rate-limiting steps in the cross-bridge cycle.

PubMed

Stehle, Robert; Tesi, Chiara

2017-08-01

A basic goal in muscle research is to understand how the cyclic ATPase activity of cross-bridges is converted into mechanical force. A direct approach to study the chemo-mechanical coupling between P i release and the force-generating step is provided by the kinetics of force response induced by a rapid change in [P i ]. Classical studies on fibres using caged-P i discovered that rapid increases in [P i ] induce fast force decays dependent on final [P i ] whose kinetics were interpreted to probe a fast force-generating step prior to P i release. However, this hypothesis was called into question by studies on skeletal and cardiac myofibrils subjected to P i jumps in both directions (increases and decreases in [P i ]) which revealed that rapid decreases in [P i ] trigger force rises with slow kinetics, similar to those of calcium-induced force development and mechanically-induced force redevelopment at the same [P i ]. A possible explanation for this discrepancy came from imaging of individual sarcomeres in cardiac myofibrils, showing that the fast force decay upon increase in [P i ] results from so-called sarcomere 'give'. The slow force rise upon decrease in [P i ] was found to better reflect overall sarcomeres cross-bridge kinetics and its [P i ] dependence, suggesting that the force generation coupled to P i release cannot be separated from the rate-limiting transition. The reasons for the different conclusions achieved in fibre and myofibril studies are re-examined as the recent findings on cardiac myofibrils have fundamental consequences for the coupling between P i release, rate-limiting steps and force generation. The implications from P i -induced force kinetics of myofibrils are discussed in combination with historical and recent models of the cross-bridge cycle.

Iron oxide nanoparticle-based magnetic resonance method to monitor release kinetics from polymeric particles with high resolution.

PubMed

Chan, Minnie; Schopf, Eric; Sankaranarayanan, Jagadis; Almutairi, Adah

2012-09-18

A new method to precisely monitor rapid release kinetics from polymeric particles using super paramagnetic iron oxide nanoparticles, specifically by measuring spin-spin relaxation time (T(2)), is reported. Previously, we have published the formulation of logic gate particles from an acid-sensitive poly-β-aminoester ketal-2 polymer. Here, a series of poly-β-aminoester ketal-2 polymers with varying hydrophobicities were synthesized and used to formulate particles. We attempted to measure fluorescence of released Nile red to determine whether the structural adjustments could finely tune the release kinetics in the range of minutes to hours; however, this standard technique did not differentiate each release rate of our series. Thus, a new method based on encapsulation of iron oxide nanoparticles was developed, which enabled us to resolve the release kinetics of our particles. Moreover, the kinetics matched the relative hydrophobicity order determined by octanol-water partition coefficients. To the best of our knowledge, this method provides the highest resolution of release kinetics to date.

Fraction of organic carbon predicts labile desorption rates of chlorinated organic pollutants in laboratory-spiked geosorbents.

PubMed

Ginsbach, Jake W; Killops, Kato L; Olsen, Robert M; Peterson, Brittney; Dunnivant, Frank M

2010-05-01

The resuspension of large volumes of sediments that are contaminated with chlorinated pollutants continues to threaten environmental quality and human health. Whereas kinetic models are more accurate for estimating the environmental impact of these events, their widespread use is substantially hampered by the need for costly, time-consuming, site-specific kinetics experiments. The present study investigated the development of a predictive model for desorption rates from easily measurable sorbent and pollutant properties by examining the relationship between the fraction of organic carbon (fOC) and labile release rates. Duplicate desorption measurements were performed on 46 unique combinations of pollutants and sorbents with fOC values ranging from 0.001 to 0.150. Labile desorption rate constants indicate that release rates predominantly depend upon the fOC in the geosorbent. Previous theoretical models, such as the macro-mesopore and organic matter (MOM) diffusion model, have predicted such a relationship but could not accurately predict the experimental rate constants collected in the present study. An empirical model was successfully developed to correlate the labile desorption rate constant (krap) to the fraction of organic material where log(krap)=0.291-0.785 . log(fOC). These results provide the first experimental evidence that kinetic pollution releases during resuspension events are governed by the fOC content in natural geosorbents. Copyright (c) 2010 SETAC.

Escherichia coli survival in, and release from, white-tailed deer feces.

PubMed

Guber, Andrey K; Fry, Jessica; Ives, Rebecca L; Rose, Joan B

2015-02-01

White-tailed deer are an important reservoir for pathogens that can contribute a large portion of microbial pollution in fragmented agricultural and forest landscapes. The scarcity of experimental data on survival of microorganisms in and release from deer feces makes prediction of their fate and transport less reliable and development of efficient strategies for environment protection more difficult. The goal of this study was to estimate parameters for modeling Escherichia coli survival in and release from deer (Odocoileus virginianus) feces. Our objectives were as follows: (i) to measure survival of E. coli in deer pellets at different temperatures, (ii) to measure kinetics of E. coli release from deer pellets at different rainfall intensities, and (iii) to estimate parameters of models describing survival and release of microorganisms from deer feces. Laboratory experiments were conducted to study E. coli survival in deer pellets at three temperatures and to estimate parameters of Chick's exponential model with temperature correction based on the Arrhenius equation. Kinetics of E. coli release from deer pellets were measured at two rainfall intensities and used to derive the parameters of Bradford-Schijven model of bacterial release. The results showed that parameters of the survival and release models obtained for E. coli in this study substantially differed from those obtained by using other source materials, e.g., feces of domestic animals and manures. This emphasizes the necessity of comprehensive studies of survival of naturally occurring populations of microorganisms in and release from wildlife animal feces in order to achieve better predictions of microbial fate and transport in fragmented agricultural and forest landscapes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Flavor release and perception in hard candy: influence of flavor compound-flavor solvent interactions.

PubMed

Schober, Amanda L; Peterson, Devin G

2004-05-05

The release kinetics of l-menthol dissolved in propylene glycol (PG), Miglyol, or 1,8-cineole (two common odorless flavor solvents differing in polarity and a hydrophobic flavor compound) were monitored from a model aqueous system via atmospheric pressure chemical ionization mass spectrometry (APCI-MS). Breath analysis was also conducted via APCI-MS to monitor release of l-menthol from hard candy that used PG and Miglyol for l-menthol incorporation. The quantities of l-menthol released when dissolved in PG or Miglyol from the model aqueous system were found to be similar and overall significantly greater in comparison to when dissolved in 1,8-cineole. Analogous results were reported by the breath analysis of hard candy. The release kinetics of l-menthol from PG or Miglyol versus from 1,8-cineole were notably more rapid and higher in quantity. Results from the sensory time-intensity study also indicated that there was no perceived difference in the overall cooling intensity between the two flavor solvent delivery systems (PG and Miglyol).

Comparison of DSMC Reaction Models with QCT Reaction Rates for Nitrogen

DTIC Science & Technology

2016-07-17

The U.S. Government is joint author of the work and has the right to use, modify, reproduce, release, perform, display, or disclose the work. 13...Distribution A: Approved for Public Release, Distribution Unlimited PA #16299 Introduction • Comparison with measurements is final goal • Validation...model verification and parameter adjustment • Four chemistry models: total collision energy (TCE), quantum kinetic (QK), vibration-dissociation favoring

Kinetic Analysis of Drug Release from Compounded Slow-release Capsules of Liothyronine Sodium (T3).

PubMed

Bakhteyar, Hamid; Cassone, Clayton; Kohan, Hamed Gilzad; Sani, Shabnam N

2017-01-01

The purpose of this study was to formulate extemporaneously compounded Liothyronine Sodium (T3) slow-release capsules and to evaluate their in vitro drug release performance. Twenty-one formulations containing T3 (7.5 µg) with various compositions of two different grades of Methocel E4M and K100M premium (30% to 90%), and/or SimpleCap/Lactose (10% to 70%) were examined. Quality assessment of the capsules was conducted by standard quality control criteria of the United States Pharmacopeia (i.e., weight variation, content uniformity) to ensure their compliance. The dissolution release profile of the formulations was evaluated using United States Pharmacopeia Apparatus type II (paddle method) at a speed of 50 rpm and temperature of 37°C in phosphate buffered saline media ( pH = 7.2 to 7.4). Aliquots from the media were taken periodically up to 24 hours and analyzed using a validated enzyme-linked immunosorbent assay method. The cumulative percentage of drug release for each formulation was fitted to eleven major release kinetic equations to determine the best-fit model of drug release, as well as the mechanism of release. Assay sensitivity was as low as 1 ng/mL and the optimal calibration range was found to be between 0 ng/mL and 7.5 ng/mL, which corresponded well with the average physiological plasma concentrations of T3. Liothyronine sodium with either SimpleCap (100%) or Methocel E4M (100%) exhibited slowrelease kinetic patterns of Peppas and Zero Order, respectively. The formulation with SimpleCap (100%) had a higher percentage of drug release (as compared to 100% Methocel E4M) within the first four hours; this formulation released 80% of the drug within 12 hours when the release was plateaued thereafter. The formulation with 30% Methocel E4M and 70% SimpleCap released 100% of the drug within the initial 12 hours and exhibited a Zero Order slow-release kinetic pattern. In general, the release kinetic rate of the formulations containing Methocel K100M appeared to be slower than Methocel E4M. This alteration may be due to a higher molecular weight and apparent viscosity of Methocel K100M. While most of the formulations were fitted to a slow-release kinetic pattern, several others including Methocel E4M 100%, 30% Methocel E4M+ 70% Simple Cap, 40% Methocel K100M+ 60% SimpleCap, 50% Methocel K100M+ 50% SimpleCap, 30% Methocel E4M+ 70% Lactose, 90% Methocel E4M+ 10% Lactose, 40% Methocel K100M+ 60% Lactose, and 50% Methocel K100M+ 50% Lactose followed an ideal slow-release kinetic pattern of Zero Order or Higuchi. The results of this study successfully demonstrated the optiomal composition of slow-release compounded capsules of T3. Future studies are warranted to evaluate the in vivo performance of the optimal formulations and to establish an in vitro-in vivo correlation. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

Demon voltammetry and analysis software: Analysis of cocaine-induced alterations in dopamine signaling using multiple kinetic measures

PubMed Central

Yorgason, Jordan T.; España, Rodrigo A.; Jones, Sara R.

2011-01-01

The fast sampling rates of fast scan cyclic voltammetry make it a favorable method for measuring changes in brain monoamine release and uptake kinetics in slice, anesthetized, and freely moving preparations. The most common analysis technique for evaluating changes in dopamine signaling uses well-established Michaelis-Menten kinetic methods that can accurately model dopamine release and uptake parameters across multiple experimental conditions. Nevertheless, over the years, many researchers have turned to other measures to estimate changes in dopamine release and uptake, yet to our knowledge no systematic comparison amongst these measures has been conducted. To address this lack of uniformity in kinetic analyses, we have created the Demon Voltammetry and Analysis software suite, which is freely available to academic and non-profit institutions. Here we present an explanation of the Demon Acquisition and Analysis features, and demonstrate its utility for acquiring voltammetric data under in vitro, in vivo anesthetized, and freely moving conditions. Additionally, the software was used to compare the sensitivity of multiple kinetic measures of release and uptake to cocaine-induced changes in electrically evoked dopamine efflux in nucleus accumbens core slices. Specifically, we examined and compared tau, full width at half height, half-life, T20, T80, slope, peak height, calibrated peak dopamine concentration, and area under the curve to the well-characterized Michaelis-Menten parameters, dopamine per pulse, maximal uptake rate, and apparent affinity. Based on observed results we recommend tau for measuring dopamine uptake and calibrated peak dopamine concentration for measuring dopamine release. PMID:21392532

An allosteric model of the molecular interactions of excitation- contraction coupling in skeletal muscle

PubMed Central

1993-01-01

A contact interaction is proposed to exist between the voltage sensor of the transverse tubular membrane of skeletal muscle and the calcium release channel of the sarcoplasmic reticulum. This interaction is given a quantitative formulation inspired in the Monod, Wyman, and Changeux model of allosteric transitions in hemoglobin (Monod, J., J. Wyman, and J.-P. Changeux. 1965. Journal of Molecular Biology. 12:88- 118), and analogous to one proposed by Marks and Jones for voltage- dependent Ca channels (Marks, T. N., and S. W. Jones. 1992. Journal of General Physiology. 99:367-390). The allosteric protein is the calcium release channel, a homotetramer, with two accessible states, closed and open. The kinetics and equilibrium of this transition are modulated by voltage sensors (dihydropyridine receptors) pictured as four units per release channel, each undergoing independent voltage-driven transitions between two states (resting and activating). For each voltage sensor that moves to the activating state, the tendency of the channel to open increases by an equal (large) factor. The equilibrium and kinetic equations of the model are solved and shown to reproduce well a number of experimentally measured relationships including: charge movement (Q) vs. voltage, open probability of the release channel (Po) vs. voltage, the transfer function relationship Po vs. Q, and the kinetics of charge movement, release activation, and deactivation. The main consequence of the assumption of allosteric coupling is that primary effects on the release channel are transmitted backward to the voltage sensor and give secondary effects. Thus, the model reproduces well the effects of perchlorate, described in the two previous articles, under the assumption that the primary effect is to increase the intrinsic tendency of the release channel to open, with no direct effects on the voltage sensor. This modification of the open-closed equilibrium of the release channel causes a shift in the equilibrium dependency of charge movement with voltage. The paradoxical slowing of charge movement by perchlorate also results from reciprocal effects of the channel on the allosterically coupled voltage sensors. The observations of the previous articles plus the simulations in this article constitute functional evidence of allosteric transmission. PMID:8245819

Simulation of the hydrodynamic conditions of the eye to better reproduce the drug release from hydrogel contact lenses: experiments and modeling.

PubMed

Pimenta, A F R; Valente, A; Pereira, J M C; Pereira, J C F; Filipe, H P; Mata, J L G; Colaço, R; Saramago, B; Serro, A P

2016-12-01

Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In this work, a microfluidic cell was designed and used to mimic the continuous, volumetric flow rate of tear fluid and its low volume. The suitable operation of the cell, in terms of uniformity and symmetry of flux, was proved using a numerical model based in the Navier-Stokes and continuity equations. The release profile of a model system (a hydroxyethyl methacrylate-based hydrogel (HEMA/PVP) for soft contact lenses (SCLs) loaded with diclofenac) obtained with the microfluidic cell was compared with that obtained in static conditions, showing that the kinetics of release in dynamic conditions is slower. The application of the numerical model demonstrated that the designed cell can be used to simulate the drug release in the whole range of the human eye tear film volume and allowed to estimate the drug concentration in the volume of liquid in direct contact with the hydrogel. The knowledge of this concentration, which is significantly different from that measured in the experimental tests during the first hours of release, is critical to predict the toxicity of the drug release system and its in vivo efficacy. In conclusion, the use of the microfluidic cell in conjunction with the numerical model shall be a valuable tool to design and optimize new therapeutic drug-loaded SCLs.

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

PubMed

Uhumwangho, M U; Okor, R S

2006-01-01

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

Controlled release hydrophilic matrix tablet formulations of isoniazid: design and in vitro studies.

PubMed

Hiremath, Praveen S; Saha, Ranendra N

2008-01-01

The aim of the present investigation was to develop oral controlled release matrix tablet formulations of isoniazid using hydroxypropyl methylcellulose (HPMC) as a hydrophilic release retardant polymer and to study the influence of various formulation factors like proportion of the polymer, polymer viscosity grade, compression force, and release media on the in vitro release characteristics of the drug. The formulations were developed using wet granulation technology. The in vitro release studies were performed using US Pharmacopoeia type 1 apparatus (basket method) in 900 ml of pH 7.4 phosphate buffer at 100 rpm. The release kinetics was analyzed using Korsmeyer-Peppas model. The release profiles were also analyzed using statistical method (one-way analysis of variance) and f (2) metric values. The release profiles found to follow Higuchi's square root kinetics model irrespective of the polymer ratio and the viscosity grade used. The results in the present investigation confirm that the release rate of the drug from the HPMC matrices is highly influenced by the drug/HPMC ratio and viscosity grade of the HPMC. Also, the effect of compression force and release media was found to be significant on the release profiles of isoniazid from HPMC matrix tablets. The release mechanism was found to be anomalous non-Fickian diffusion in all the cases. In the present investigation, a series of controlled release formulations of isoniazid were developed with different release rates and duration so that these formulations could further be assessed from the in vivo bioavailability studies. The formulations were found to be stable and reproducible.

Development and evaluation of intestinal targeted mucoadhesive microspheres of Bacillus coagulans.

PubMed

Alli, Sk Md Athar; Ali, Sk Md Ajhar; Samanta, Amalesh

2011-11-01

Intestinal targeted mucoadhesive microsphere of probiotics may provide numerous associated health benefits. To develop mucoadhesive microspheres that will deliver viable probiotic cells into gut protectively against harsh environmental conditions of stomach for extended period. Core mucoadhesive microspheres of Bacillus coagulans were prepared using hypromellose, following coacervation and phase separation technique and were then coated with hypromellose phthalate to achieve their site-specific release. Microspheres were evaluated for percent yield, entrapment efficiency, surface morphology, particle size and size distribution, flow property, swelling property, mucoadhesion property by the in vitro wash-off and the ex vivo mucoadhesive strength tests, in vitro release profile and release kinetic, in vivo probiotic activity, and stability. The values for kinetic constant and regression coefficient of model-dependent approaches and the difference factor, the similarity factor, and the Rescigno index of model-independent approaches were determined for accessing and comparing in vitro performance. Microsphere formulation batches have percent yield value between 56.26% and 69.13% and entrapment efficiency value between 66.95% and 77.89%. Microspheres were coarser with spherical shape having mean particle size from 28.03 to 48.31 μm. In vitro B. coagulans release profile follows zero-order kinetics and depends on the grade of hypromellose and the B. coagulans-to-hypromellose ratio. Experimental microspheres rendered adequate stability to B. coagulans at room temperature. Microspheres had delivered B. coagulans in simulated intestinal condition following zero-order kinetics, protectively in simulated gastric condition, exhibiting appreciable mucoadhesion in intestinal condition, which could be useful to achieve site-specific delivery for extended period.

Kinetics of Brominated Flame Retardant (BFR) Releases from Granules of Waste Plastics.

PubMed

Sun, Bingbing; Hu, Yuanan; Cheng, Hefa; Tao, Shu

2016-12-20

Plastic components of e-waste contain high levels of brominated flame retardants (BFRs), whose releases cause environmental and human health concerns. This study characterized the release kinetics of polybrominated diphenyl ethers (PBDEs) from millimeter-sized granules processed from the plastic exteriors of two scrap computer displays at environmentally relevant temperatures. The release rate of a substitute of PBDEs, 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), from the waste plastics, was reported for the first time. Deca-BDE was the most abundant PBDE congeners in both materials (87-89%), while BTBPE was also present at relatively high contents. The release kinetics of BFRs could be modeled as one-dimensional diffusion, while the temperature dependence of diffusion coefficients was well described by the Arrhenius equation. The diffusion coefficients of BFRs (at 30 °C) in the plastic matrices were estimated to be in the range of 10 -27.16 to 10 -19.96 m 2 ·s -1 , with apparent activation energies between 88.4 and 154.2 kJ·mol -1 . The half-lives of BFR releases (i.e., 50% depletion) from the plastic granules ranged from thousands to tens of billions of years at ambient temperatures. These findings suggest that BFRs are released very slowly from the matrices of waste plastics through molecular diffusion, while their emissions can be significantly enhanced with wear-and-tear and pulverization.

Transport direction determines the kinetics of substrate transport by the glutamate transporter EAAC1

PubMed Central

Zhang, Zhou; Tao, Zhen; Gameiro, Armanda; Barcelona, Stephanie; Braams, Simona; Rauen, Thomas; Grewer, Christof

2007-01-01

Glutamate transport by the excitatory amino acid carrier EAAC1 is known to be reversible. Thus, glutamate can either be taken up into cells, or it can be released from cells through reverse transport, depending on the electrochemical gradient of the co- and countertransported ions. However, it is unknown how fast and by which reverse transport mechanism glutamate can be released from cells. Here, we determined the steady- and pre-steady-state kinetics of reverse glutamate transport with submillisecond time resolution. First, our results suggest that glutamate and Na+ dissociate from their cytoplasmic binding sites sequentially, with glutamate dissociating first, followed by the three cotransported Na+ ions. Second, the kinetics of glutamate transport depend strongly on transport direction, with reverse transport being faster but less voltage-dependent than forward transport. Third, electrogenicity is distributed over several reverse transport steps, including intracellular Na+ binding, reverse translocation, and reverse relocation of the K+-bound EAAC1. We propose a kinetic model, which is based on a “first-in-first-out” mechanism, suggesting that glutamate association, with its extracellular binding site as well as dissociation from its intracellular binding site, precedes association and dissociation of at least one Na+ ion. Our model can be used to predict rates of glutamate release from neurons under physiological and pathophysiological conditions. PMID:17991780

Development and evaluation of natural gum-based extended release matrix tablets of two model drugs of different water solubilities by direct compression.

PubMed

Ofori-Kwakye, Kwabena; Mfoafo, Kwadwo Amanor; Kipo, Samuel Lugrie; Kuntworbe, Noble; Boakye-Gyasi, Mariam El

2016-01-01

The study was aimed at developing extended release matrix tablets of poorly water-soluble diclofenac sodium and highly water-soluble metformin hydrochloride by direct compression using cashew gum, xanthan gum and hydroxypropylmethylcellulose (HPMC) as release retardants. The suitability of light grade cashew gum as a direct compression excipient was studied using the SeDeM Diagram Expert System. Thirteen tablet formulations of diclofenac sodium (∼100 mg) and metformin hydrochloride (∼200 mg) were prepared with varying amounts of cashew gum, xanthan gum and HPMC by direct compression. The flow properties of blended powders and the uniformity of weight, crushing strength, friability, swelling index and drug content of compressed tablets were determined. In vitro drug release studies of the matrix tablets were conducted in phosphate buffer (diclofenac: pH 7.4; metformin: pH 6.8) and the kinetics of drug release was determined by fitting the release data to five kinetic models. Cashew gum was found to be suitable for direct compression, having a good compressibility index (ICG) value of 5.173. The diclofenac and metformin matrix tablets produced generally possessed fairly good physical properties. Tablet swelling and drug release in aqueous medium were dependent on the type and amount of release retarding polymer and the solubility of drug used. Extended release of diclofenac (∼24 h) and metformin (∼8-12 h) from the matrix tablets in aqueous medium was achieved using various blends of the polymers. Drug release from diclofenac tablets fitted zero order, first order or Higuchi model while release from metformin tablets followed Higuchi or Hixson-Crowell model. The mechanism of release of the two drugs was mostly through Fickian diffusion and anomalous non-Fickian diffusion. The study has demonstrated the potential of blended hydrophilic polymers in the design and optimization of extended release matrix tablets for soluble and poorly soluble drugs by direct compression.

Preparation of starch nanoparticles loaded with quercetin using nanoprecipitation technique.

PubMed

Farrag, Yousof; Ide, Walther; Montero, Belén; Rico, Maite; Rodríguez-Llamazares, Saddys; Barral, Luis; Bouza, Rebeca

2018-07-15

Nanoparticles of starches from different botanical origin were prepared by nanoprecipitation using 0.1M hydrochloric acid as non-solvent. The morphology and the particle size were analyzed using field emission scanning electron microscopy and dynamic light scattering. The nanoparticles were spherical and their sizes vary depending on the origin and the concentration of the starch solution. Starch nanoparticles loaded with quercetin were prepared. In-vitro release studies of the quercetin from the starch nanoparticles were performed in 35% ethanol as a release medium. The starch origin affects the quercetin loading percentage, the release kinetics and the antioxidant activity of the produced nanoparticles. The starch-quercetin nanoparticles from cereal origin showed the lowest loading percentage and the lowest fraction released of quercetin in comparison with nanoparticles from tuber and legume origin. The release kinetics seem to be controlled mainly by Fickian diffusion which have been revealed fitting the release data to the Peppas-Sahlin model. Copyright © 2018 Elsevier B.V. All rights reserved.

Load and Pi control flux through the branched kinetic cycle of myosin V.

PubMed

Kad, Neil M; Trybus, Kathleen M; Warshaw, David M

2008-06-20

Myosin V is a processive actin-based motor protein that takes multiple 36-nm steps to deliver intracellular cargo to its destination. In the laser trap, applied load slows myosin V heavy meromyosin stepping and increases the probability of backsteps. In the presence of 40 mm phosphate (P(i)), both forward and backward steps become less load-dependent. From these data, we infer that P(i) release commits myosin V to undergo a highly load-dependent transition from a state in which ADP is bound to both heads and its lead head trapped in a pre-powerstroke conformation. Increasing the residence time in this state by applying load increases the probability of backstepping or detachment. The kinetics of detachment indicate that myosin V can detach from actin at two distinct points in the cycle, one of which is turned off by the presence of P(i). We propose a branched kinetic model to explain these data. Our model includes P(i) release prior to the most load-dependent step in the cycle, implying that P(i) release and load both act as checkpoints that control the flux through two parallel pathways.

Understanding controlled drug release from mesoporous silicates: theory and experiment.

PubMed

Ukmar, T; Maver, U; Planinšek, O; Kaučič, V; Gaberšček, M; Godec, A

2011-11-07

Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes. Copyright © 2011 Elsevier B.V. All rights reserved.

Application of time-resolved fluorescence for direct and continuous probing of release from polymeric delivery vehicles.

PubMed

Viger, Mathieu L; Sheng, Wangzhong; McFearin, Cathryn L; Berezin, Mikhail Y; Almutairi, Adah

2013-11-10

Though accurately evaluating the kinetics of release is critical for validating newly designed therapeutic carriers for in vivo applications, few methods yet exist for release measurement in real time and without the need for any sample preparation. Many of the current approaches (e.g. chromatographic methods, absorption spectroscopy, or NMR spectroscopy) rely on isolation of the released material from the loaded vehicles, which require additional sample purification and can lead to loss of accuracy when probing fast kinetics of release. In this study we describe the use of time-resolved fluorescence for in situ monitoring of small molecule release kinetics from biodegradable polymeric drug delivery systems. This method relies on the observation that fluorescent reporters being released from polymeric drug delivery systems possess distinct excited-state lifetime components, reflecting their different environments in the particle suspensions, i.e., confined in the polymer matrices or free in the aqueous environment. These distinct lifetimes enable real-time quantitative mapping of the relative concentrations of dye in each population to obtain precise and accurate temporal information on the release profile of particular carrier/payload combinations. We found that fluorescence lifetime better distinguishes subtle differences in release profiles (e.g. differences associated with dye loading) than conventional steady-state fluorescence measurements, which represent the averaged dye behavior over the entire scan. Given the method's applicability to both hydrophobic and hydrophilic cargo, it could be employed to model the release of any drug-carrier combination. Copyright © 2013 Elsevier B.V. All rights reserved.

Transient Kinetics Define a Complete Kinetic Model for Protein Arginine Methyltransferase 1*

PubMed Central

Hu, Hao; Luo, Cheng; Zheng, Y. George

2016-01-01

Protein arginine methyltransferases (PRMTs) are the enzymes responsible for posttranslational methylation of protein arginine residues in eukaryotic cells, particularly within the histone tails. A detailed mechanistic model of PRMT-catalyzed methylation is currently lacking, but it is essential for understanding the functions of PRMTs in various cellular pathways and for efficient design of PRMT inhibitors as potential treatments for a range of human diseases. In this work, we used stopped-flow fluorescence in combination with global kinetic simulation to dissect the transient kinetics of PRMT1, the predominant type I arginine methyltransferase. Several important mechanistic insights were revealed. The cofactor and the peptide substrate bound to PRMT1 in a random manner and then followed a kinetically preferred pathway to generate the catalytic enzyme-cofactor-substrate ternary complex. Product release proceeded in an ordered fashion, with peptide dissociation followed by release of the byproduct S-adenosylhomocysteine. Importantly, the dissociation rate of the monomethylated intermediate from the ternary complex was much faster than the methyl transfer. Such a result provided direct evidence for distributive arginine dimethylation, which means the monomethylated substrate has to be released to solution and rebind with PRMT1 before it undergoes further methylation. In addition, cofactor binding involved a conformational transition, likely an open-to-closed conversion of the active site pocket. Further, the histone H4 peptide bound to the two active sites of the PRMT1 homodimer with differential affinities, suggesting a negative cooperativity mechanism of substrate binding. These findings provide a new mechanistic understanding of how PRMTs interact with their substrates and transfer methyl groups. PMID:27834681

Formulation and in vitro evaluation of sustained release matrix tablets using cross-linked natural gum.

PubMed

Jamil, Qurratul Ain; Masood, Muhammad Irfan; Jamil, Muhammad Nauman; Masood, Imran; Iqbal, Shahid Muhammad

2017-03-01

Polysaccharide gums because of their biocompatibility, biodegradability and non-immunogenic properties are considered as the best choice for preparing sustained release tablets as compared to their synthetic counterpart. The cross linking of natural gums in matrix tablets increase the sustained release property of matrix tablets. Isoniazid is a first line therapy of tuberculosis, belongs to BCS I with half-life of 3-4 hours. These characteristics make isoniazid a good candidate for sustained release dosage form. Karaya gum crossed linked with trisodium tri metaphosphate was used as release rate retardant for preparing isoniazid cross-linked matrix tablet. Total 8 sustained release formulations were prepared. Both granules and tablets were evaluated under in vitro condition against different parameters. Dissolution studies were performed with all eight formulations for 12 hours using USP apparatus I. Four formulations designated as F1, F2, F3, F4 have drug and karaya gum while other four formulations F5, F6, F7, F8 have drug and crossed linked polymer in ratios of 1:1, 1:2, 1:3 and 1:4 respectively. Dissolution data was analyzed by using different kinetic models. Best fit model for most efficient formulation was zero order while release mechanism was super case I. Formulation 8 showed sufficiently slow release kinetics and about 83% of drug was released in 10 hours, indicating that cross-linked karaya gum proved efficient in preparing sustained release tablets.

Kinetics and mechanism of release from glyceryl monostearate-based implants: evaluation of release in a gel simulating in vivo implantation.

PubMed

Allababidi, S; Shah, J C

1998-06-01

The overall objective of the study was to design an implantable delivery system based on glyceryl monostearate (GMS) for the site-specific delivery of antibiotics for the prevention of surgical wound infection. To design the implant, a release method had to be developed that simulate the in vivo implantation conditions to be able to predict the release characteristics from the implants when they are actually used in vivo. Also, identifying the release kinetics and mechanism and evaluating the factors that influence the release of drugs from the GMS-based matrix were necessary to allow further design of implants that could yield a desired release rate. The release of cefazolin was monitored from GMS matrixes implanted into agar gel, simulating subcutaneous tissues with respect to viscosity and water content. The gel method resulted in observation of spatial and temporal concentration profiles in the immediate vicinity of the implants, indicating the benefits of local drug delivery; however, there was no significant difference between the cumulative release profiles by the gel method or the vial release method. The release of cefazolin from the GMS-based matrix with the vial method followed Higuchi's square root of time kinetics. The release rate was found to be directly proportional to cefazolin load (A) and the surface area (SA) of the matrix as expressed by the following equation: = 0.24ASA. On the basis of this equation, one can design a variety of GMS matrixes that would result in a desired release rate or release duration. This also indicated that cefazolin release followed the release kinetics of a freely soluble drug from an insoluble matrix and hence it is a diffusion-controlled process. The effect of drug solubility on the release kinetics was determined by comparing the release kinetics of the poorly water soluble ciprofloxacin (0.16 mg/mL) to that of the highly water soluble cefazolin (325 mg/mL). The release duration of ciprofloxacin (80 h) was longer than that of cefazolin (25 h) from identical GMS matrixes. Although ciprofloxacin release was initially controlled by the matrix, agitation accelerated disintegration of the matrix and release due to its poor solubility, and ciprofloxacin release appeared to be a dissolution-controlled process following zero-order release kinetics.

Effect of hydrophobic inclusions on polymer swelling kinetics studied by magnetic resonance imaging.

PubMed

Gajdošová, Michaela; Pěček, Daniel; Sarvašová, Nina; Grof, Zdeněk; Štěpánek, František

2016-03-16

The rate of drug release from polymer matrix-based sustained release formulations is often controlled by the thickness of a gel layer that forms upon contact with dissolution medium. The effect of formulation parameters on the kinetics of elementary rate processes that contribute to gel layer formation, such as water ingress, polymer swelling and erosion, is therefore of interest. In the present work, gel layer formation has been investigated by magnetic resonance imaging (MRI), which is a non-destructive method allowing direct visualization of effective water concentration inside the tablet and its surrounding. Using formulations with Levetiracetam as the active ingredient, HPMC as a hydrophilic matrix former and carnauba wax (CW) as a hydrophobic component in the matrix system, the effect of different ratios of these two ingredients on the kinetics of gel formation (MRI) and drug release (USP 4 like dissolution test) has been investigated and interpreted using a mathematical model. Copyright © 2016 Elsevier B.V. All rights reserved.

Controlled release of Doxycycline from gum acacia/poly(sodium acrylate) microparticles for oral drug delivery.

PubMed

Bajpai, S K; Jadaun, Mamta; Bajpai, M; Jyotishi, Pooja; Shah, Farhan Ferooz; Tiwari, Seema

2017-11-01

In the present work, Doxycycline loaded gum acacia (GA)/poly(sodium acrylate) (SA) hydrogels were prepared for the oral drug delivery of model drug Doxycycline. The hydrogels were characterized by X-ray diffraction analysis (XRD), Fourier transform infrared spectroscopy (FTIR) scanning electron microscopy (SEM) and Zeta potential. The dynamic release of Doxycycline was investigated in the physiological fluids at 37°C. Various kinetic models such as Power function model, Schott model and Higuchi model were applied to interpret the release data. Schott model was found to be most fitted. The Doxycycline loaded hydrogels were tested for their antibacterial action against E. coli. Copyright © 2017 Elsevier B.V. All rights reserved.

Pharmaceutical Product Lead Optimization for Better In vivo Bioequivalence Performance: A case study of Diclofenac Sodium Extended Release Matrix Tablets.

PubMed

Shahiwala, Aliasgar; Zarar, Aisha

2018-01-01

In order to prove the validity of a new formulation, a considerable amount of effort is required to study bioequivalence, which not only increases the burden of carrying out a number of bioequivalence studies but also eventually increases the cost of the optimization process. The aim of the present study was to develop sustained release matrix tablets containing diclofenac sodium using natural polymers and to demonstrate step by step process of product development till the prediction of in vivo marketed product equivalence of the developed product. Different batches of tablets were prepared by direct compression. In vitro drug release studies were performed as per USP. The drug release data were assessed using model-dependent, modelindependent and convolution approaches. Drug release profiles showed that extended release action were in the following order: Gum Tragacanth > Sodium Alginate > Gum Acacia. Amongst the different batches prepared, only F1 and F8 passed the USP criteria of drug release. Developed formulas were found to fit Higuchi kinetics model with Fickian (case I) diffusion-mediated release mechanism. Model- independent kinetics confirmed that total of four batches were passed depending on the similarity factors based on the comparison with the marketed Diclofenac. The results of in vivo predictive convolution model indicated that predicted AUC, Cmax and Tmax values for batch F8 were similar to that of marketed product. This study provides simple yet effective outline of pharmaceutical product development process that will minimize the formulation development trials and maximize the product success in bioequivalence studies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Preparation and evaluation of novel metronidazole sustained release and floating matrix tablets.

PubMed

Asnaashari, Solmaz; Khoei, Nazaninossadat Seyed; Zarrintan, Mohammad Hosein; Adibkia, Khosro; Javadzadeh, Yousef

2011-08-01

In the present study, metronidazole was used for preparing floating dosage forms that are designed to retain in the stomach for a long time and have developed as a drug delivery system for better eradication of Helicobacter Pylori in peptic ulcer diseases. For this means, various formulations were designed using multi-factorial design. HPMC, psyllium and carbopol in different concentrations were used as floating agents, and sodium bicarbonate was added as a gas-forming agent. Hardness, friability, drug loading, floating ability and release profiles as well as kinetics of release were assessed. Formulations containing HPMC as filler showed prolonged lag times for buoyancy. Adding psyllium to these formulations had reduced relative lag times. Overall, selected formulations were able to float immediately and showed buoyancy for at least 8?h. Meanwhile, sustained profiles of drug release were also obtained. Kinetically, among the 10 assessed models, the release pattern of metronidazole from the tablets fitted best to Power law, Weibull and Higuchi models in respect overall to mean percentage error values of 3.8, 4.73 and 5.77, respectively, for calcium carbonate-based tablets and, 2.95, 6.39 and 3.9, respectively, for calcium silicate-based tablets. In general, these systems can float in the gastric condition and control the drug release from the tablets.

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

Barani, T.; Bruschi, E.; Pizzocri, D.

The modelling of fission gas behaviour is a crucial aspect of nuclear fuel analysis in view of the related effects on the thermo-mechanical performance of the fuel rod, which can be particularly significant during transients. Experimental observations indicate that substantial fission gas release (FGR) can occur on a small time scale during transients (burst release). To accurately reproduce the rapid kinetics of burst release in fuel performance calculations, a model that accounts for non-diffusional mechanisms such as fuel micro-cracking is needed. In this work, we present and assess a model for transient fission gas behaviour in oxide fuel, which ismore » applied as an extension of diffusion-based models to allow for the burst release effect. The concept and governing equations of the model are presented, and the effect of the newly introduced parameters is evaluated through an analytic sensitivity analysis. Then, the model is assessed for application to integral fuel rod analysis. The approach that we take for model assessment involves implementation in two structurally different fuel performance codes, namely, BISON (multi-dimensional finite element code) and TRANSURANUS (1.5D semi-analytic code). The model is validated against 19 Light Water Reactor fuel rod irradiation experiments from the OECD/NEA IFPE (International Fuel Performance Experiments) database, all of which are simulated with both codes. The results point out an improvement in both the qualitative representation of the FGR kinetics and the quantitative predictions of integral fuel rod FGR, relative to the canonical, purely diffusion-based models, with both codes. The overall quantitative improvement of the FGR predictions in the two codes is comparable. Furthermore, calculated radial profiles of xenon concentration are investigated and compared to experimental data, demonstrating the representation of the underlying mechanisms of burst release by the new model.« less

Pre-Steady State Kinetic Analysis of cis-3-Chloroacrylic Acid Dehalogenase: Analysis and Implications†

PubMed Central

Robertson, Brooklyn A.; Schroeder, Gottfried K.; Jin, Zhinan; Johnson, Kenneth A.; Whitman, Christian P.

2009-01-01

Isomer-specific 3-chloroacrylic acid dehalogenases catalyze the hydrolytic dehalogenation of the cis- and trans-isomers of 3-chloroacrylate to yield malonate semialdehyde. These reactions represent key steps in the degradation of the nematocide, 1,3-dichloropropene. The kinetic mechanism of cis-3-chloroacrylic acid dehalogenase (cis-CaaD) has now been examined using stopped-flow and chemical-quench techniques. Stopped-flow analysis of the reaction, following the fluorescence of an active site tryptophan, is consistent with a minimal three-step model involving substrate binding, chemistry, and product release. Chemical quench experiments show burst kinetics, indicating that product release is at least partially rate limiting. Global fitting of all of the kinetic results by simulation is best accommodated by a four-step mechanism. In the final kinetic model, the enzyme binds substrate and isomerizes to an alternate fluorescent form, chemistry occurs, and is followed by the ordered release of two products, with the release of the first product as the rate-limiting step. Bromide ion is a competitive inhibitor of the reaction indicating that it binds to the free enzyme rather than to the enzyme with one product still bound. This observation suggests that malonate semialdehyde is the first product released by the enzyme (rate limiting), followed by halide. A comparison of the unliganded cis-CaaD crystal structure with that of an inactivated cis-CaaD where the prolyl nitrogen of Pro-1 is covalently attached to (R)-2-hydroxypropanoate provides a possible explanation for the isomerization step. The structure of the covalently modified enzyme shows that a 7-residue loop comprised of residues 32-38 is closed down on the active site cavity where the backbone amides of two residues (Phe-37 and Leu-38) interact with the carboxylate group of the adduct. In the unliganded form, the same loop points away from the active site cavity. Similarly, substrate binding may cause this loop to close down on the active site and sequester the reaction from the external environment. PMID:19856961

The stability of gadolinium-based contrast agents in human serum: A reanalysis of literature data and association with clinical outcomes.

PubMed

Prybylski, John P; Semelka, Richard C; Jay, Michael

2017-05-01

To reanalyze literature data of gadolinium (Gd)-based contrast agents (GBCAs) in plasma with a kinetic model of dissociation to provide a comprehensive assessment of equilibrium conditions for linear GBCAs. Data for the release of Gd from GBCAs in human serum was extracted from a previous report in the literature and fit to a kinetic dissociation/association model. The conditional stabilities (logK cond ) and percent intact over time were calculated using the model rate constants. The correlations between clinical outcomes and logK cond or other stability indices were determined. The release curves for Omniscan®, gadodiamide, OptiMARK®, gadoversetamide Magnevist® and Multihance® were extracted and all fit well to the kinetic model. The logK cond s calculated from the rate constants were on the order of ~4-6, and were not significantly altered by excess ligand or phosphate. The stability constant based on the amount intact by the initial elimination half-life of GBCAs in plasma provided good correlation with outcomes observed in patients. Estimation of the kinetic constants for GBCA dissociation/association revealed that their stability in physiological fluid is much lower than previous approaches would suggest, which correlates well with deposition and pharmacokinetic observations of GBCAs in human patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Kinetic Release of Alkalinity from Particle-Containing Oil-in-Water Emulsions

NASA Astrophysics Data System (ADS)

Muller, K.; Chapra, S. C.; Ramsburg, A.

2014-12-01

Oil-in-water emulsions are typically employed during remediation to promote biotic reduction of contaminants. Emulsions, however, hold promise for encapsulated delivery of many types of active ingredients required for successful site remediation or long-term site stewardship. Our research is currently focused on using alkalinity-containing particles held within oil-in-water emulsions to sustain control of subsurface pH. Here we describe results from laboratory experiments and mathematical modeling conducted to quantify the kinetics associated with the emulsion delivery and alkalinity release process. Kinetically stable oil-in-water emulsions containing (~60 nmCaCO3 or ~100 nm MgO particles) were previously developed using soybean oil and Gum Arabic as a stabilizing agent. Batch and column experiments were employed to assess the accessibility and release of the alkalinity from the emulsion. Successive additions of HCl were used in batch systems to produce several pH responses (pH rebounds) that were subsequently modeled to elucidate release mechanisms and rates for varying emulsion compositions and particle types. Initial results suggest that a linear-driving-force model is generally able to capture the release behavior in the batch system when the temporally-constant, lumped mass-transfer coefficient is scaled by the fraction of particle mass remaining within the droplets. This result suggests that the rate limiting step in the release process may be the interphase transfer of reactive species at the oil-water interface. 1-d column experiments were also completed in order to quantify the extent and rate of alkalinity release from emulsion droplets retained in a sandy medium. Alkalinity release from the retained droplets treated a pH 4 influent water for 25-60 pore volumes (the duration depended on particle type and mass loading), and the cessation in treatment corresponded to exhaustion of the particle mass held within the oil. Column experiments were simulated using a transport code containing the linear-driving-force expression evaluated in the batch experiments. In these simulations the lumped mass transfer coefficient was fit and compared with values predicted using existing correlations for liquid-liquid and solid-liquid interfaces in porous media.

Preparation and Properties of a Novel Semi-IPN Slow-Release Fertilizer with the Function of Water Retention.

PubMed

Xiang, Yang; Ru, Xudong; Shi, Jinguo; Song, Jiang; Zhao, Haidong; Liu, Yaqing; Guo, Dongdong; Lu, Xin

2017-12-20

A new semi-interpenetrating polymer network (semi-IPN) slow-release fertilizer (SISRF) with water absorbency, based on the kaolin-g-poly(acrylic acid-co-acrylic amide) (kaolin-g-P(AA-co-AM)) network and linear urea-formaldehyde oligomers (UF), was prepared by solution polymerization. Nutrients phosphorus and potassium were supplied by adding dipotassium hydrogen phosphate during the preparation process. The structure and properties of SISRF were characterized by various characterization methods. SISRF showed excellent water absorbency of 68 g g -1 in tap water. The slow-release behavior of nutrients and water-retention capacity of SISRF were also measured. Meanwhile, the swelling kinetics was well described by a pseudo-second-order kinetics model. Results suggested the formation of SISRF with simultaneously good slow-release and water-retention capacity, which was expected to apply in modern agriculture and horticulture.

The water kinetics of superabsorbent polymers during cement hydration and internal curing visualized and studied by NMR.

PubMed

Snoeck, D; Pel, L; De Belie, N

2017-08-25

SuperAbsorbent Polymers (SAPs) can be applied as an admixture in cementitious materials. As the polymers are able to swell, they will absorb part of the mixing water and can then release that water back towards the cementitious matrix for internal curing. This is interesting in terms of autogenous shrinkage mitigation as the internal relative humidity is maintained. The mechanism is theoretically described by the Powers and Brownyard model, but the kinetics and water release still remain subject of detailed investigation. This paper uses Nuclear Magnetic Resonance (NMR) to study the release of water from the superabsorbent polymers towards the cementitious matrix during cement hydration. The release of water by the SAPs is monitored as a function of time and degree of hydration. The internal humidity is also monitored in time by means of sensitive relative-humidity sensors.

Evaluation of a hybrid kinetics/mixing-controlled combustion model for turbulent premixed and diffusion combustion using KIVA-II

NASA Technical Reports Server (NTRS)

Nguyen, H. Lee; Wey, Ming-Jyh

1990-01-01

Two-dimensional calculations were made of spark ignited premixed-charge combustion and direct injection stratified-charge combustion in gasoline fueled piston engines. Results are obtained using kinetic-controlled combustion submodel governed by a four-step global chemical reaction or a hybrid laminar kinetics/mixing-controlled combustion submodel that accounts for laminar kinetics and turbulent mixing effects. The numerical solutions are obtained by using KIVA-2 computer code which uses a kinetic-controlled combustion submodel governed by a four-step global chemical reaction (i.e., it assumes that the mixing time is smaller than the chemistry). A hybrid laminar/mixing-controlled combustion submodel was implemented into KIVA-2. In this model, chemical species approach their thermodynamics equilibrium with a rate that is a combination of the turbulent-mixing time and the chemical-kinetics time. The combination is formed in such a way that the longer of the two times has more influence on the conversion rate and the energy release. An additional element of the model is that the laminar-flame kinetics strongly influence the early flame development following ignition.

Evaluation of a hybrid kinetics/mixing-controlled combustion model for turbulent premixed and diffusion combustion using KIVA-2

NASA Technical Reports Server (NTRS)

Nguyen, H. Lee; Wey, Ming-Jyh

1990-01-01

Two dimensional calculations were made of spark ignited premixed-charge combustion and direct injection stratified-charge combustion in gasoline fueled piston engines. Results are obtained using kinetic-controlled combustion submodel governed by a four-step global chemical reaction or a hybrid laminar kinetics/mixing-controlled combustion submodel that accounts for laminar kinetics and turbulent mixing effects. The numerical solutions are obtained by using KIVA-2 computer code which uses a kinetic-controlled combustion submodel governed by a four-step global chemical reaction (i.e., it assumes that the mixing time is smaller than the chemistry). A hybrid laminar/mixing-controlled combustion submodel was implemented into KIVA-2. In this model, chemical species approach their thermodynamics equilibrium with a rate that is a combination of the turbulent-mixing time and the chemical-kinetics time. The combination is formed in such a way that the longer of the two times has more influence on the conversion rate and the energy release. An additional element of the model is that the laminar-flame kinetics strongly influence the early flame development following ignition.

Analysis of transient fission gas behaviour in oxide fuel using BISON and TRANSURANUS

NASA Astrophysics Data System (ADS)

Barani, T.; Bruschi, E.; Pizzocri, D.; Pastore, G.; Van Uffelen, P.; Williamson, R. L.; Luzzi, L.

2017-04-01

The modelling of fission gas behaviour is a crucial aspect of nuclear fuel performance analysis in view of the related effects on the thermo-mechanical performance of the fuel rod, which can be particularly significant during transients. In particular, experimental observations indicate that substantial fission gas release (FGR) can occur on a small time scale during transients (burst release). To accurately reproduce the rapid kinetics of the burst release process in fuel performance calculations, a model that accounts for non-diffusional mechanisms such as fuel micro-cracking is needed. In this work, we present and assess a model for transient fission gas behaviour in oxide fuel, which is applied as an extension of conventional diffusion-based models to introduce the burst release effect. The concept and governing equations of the model are presented, and the sensitivity of results to the newly introduced parameters is evaluated through an analytic sensitivity analysis. The model is assessed for application to integral fuel rod analysis by implementation in two structurally different fuel performance codes: BISON (multi-dimensional finite element code) and TRANSURANUS (1.5D code). Model assessment is based on the analysis of 19 light water reactor fuel rod irradiation experiments from the OECD/NEA IFPE (International Fuel Performance Experiments) database, all of which are simulated with both codes. The results point out an improvement in both the quantitative predictions of integral fuel rod FGR and the qualitative representation of the FGR kinetics with the transient model relative to the canonical, purely diffusion-based models of the codes. The overall quantitative improvement of the integral FGR predictions in the two codes is comparable. Moreover, calculated radial profiles of xenon concentration after irradiation are investigated and compared to experimental data, illustrating the underlying representation of the physical mechanisms of burst release.

Polymeric nanoparticles containing diazepam: preparation, optimization, characterization, in-vitro drug release and release kinetic study

NASA Astrophysics Data System (ADS)

Bohrey, Sarvesh; Chourasiya, Vibha; Pandey, Archna

2016-03-01

Nanoparticles formulated from biodegradable polymers like poly(lactic-co-glycolic acid) (PLGA) are being extensively investigated as drug delivery systems due to their two important properties such as biocompatibility and controlled drug release characteristics. The aim of this work to formulated diazepam loaded PLGA nanoparticles by using emulsion solvent evaporation technique. Polyvinyl alcohol (PVA) is used as stabilizing agent. Diazepam is a benzodiazepine derivative drug, and widely used as an anticonvulsant in the treatment of various types of epilepsy, insomnia and anxiety. This work investigates the effects of some preparation variables on the size and shape of nanoparticles prepared by emulsion solvent evaporation method. These nanoparticles were characterized by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM). Zeta potential study was also performed to understand the surface charge of nanoparticles. The drug release from drug loaded nanoparticles was studied by dialysis bag method and the in vitro drug release data was also studied by various kinetic models. The results show that sonication time, polymer content, surfactant concentration, ratio of organic to aqueous phase volume, and the amount of drug have an important effect on the size of nanoparticles. Hopefully we produced spherical shape Diazepam loaded PLGA nanoparticles with a size range under 250 nm with zeta potential -23.3 mV. The in vitro drug release analysis shows sustained release of drug from nanoparticles and follow Korsmeyer-Peppas model.

Synthesis, characterization and in vitro cytotoxicity analysis of a novel cellulose based drug carrier for the controlled delivery of 5-fluorouracil, an anticancer drug

NASA Astrophysics Data System (ADS)

Anirudhan, Thayyath S.; Nima, Jayachandran; Divya, Peethambaran L.

2015-11-01

The present investigation concerns the development and evaluation of a novel drug delivery system, aminated-glycidylmethacrylate grafted cellulose-grafted polymethacrylic acid-succinyl cyclodextrin (Cell-g-(GMA/en)-PMA-SCD) for the controlled release of 5-Fluorouracil, an anticancer drug. The prepared drug carrier was characterized by FT-IR, XRD and SEM techniques. Binding kinetics and isotherm studies of 5-FU onto Cell-g-(GMA/en)-PMA-SCD were found to follow pseudo-second-order and Langmuir model respectively. Maximum binding capacity of drug carrier was found to be 149.09 mg g-1 at 37 °C. Swelling studies, in vitro release kinetics, drug loading efficiency and encapsulation efficiency of Cell-g-(GMA/en)-PMA-SCD were studied. The release kinetics was analyzed using Ritger-Peppas equation at pH 7.4. Cytotoxicity analysis on MCF-7 (human breast carcinoma) cells indicated that the drug carrier shows sustained and controlled release of drug to the target site. Hence, it is evident from this investigation that Cell-g-(GMA/en)-PMA-SCD could be a promising carrier for 5-FU.

Kinetic Studies of Calcium-Induced Calcium Release in Cardiac Sarcoplasmic Reticulum Vesicles

PubMed Central

Sánchez, Gina; Hidalgo, Cecilia; Donoso, Paulina

2003-01-01

Fast Ca2+ release kinetics were measured in cardiac sarcoplasmic reticulum vesicles actively loaded with Ca2+. Release was induced in solutions containing 1.2 mM free ATP and variable free [Ca2+] and [Mg2+]. Release rate constants (k) were 10-fold higher at pCa 6 than at pCa 5 whereas Ryanodine binding was highest at pCa ≤5. These results suggest that channels respond differently when exposed to sudden [Ca2+] changes than when exposed to Ca2+ for longer periods. Vesicles with severalfold different luminal calcium contents exhibited double exponential release kinetics at pCa 6, suggesting that channels undergo time-dependent activity changes. Addition of Mg2+ produced a marked inhibition of release kinetics at pCa 6 (K0.5 = 63 μM) but not at pCa 5. Coexistence of calcium activation and inhibition sites with equally fast binding kinetics is proposed to explain this behavior. Thimerosal activated release kinetics at pCa 5 at all [Mg2+] tested and increased at pCa 6 the K0.5 for Mg2+ inhibition, from 63 μM to 136 μM. We discuss the possible relevance of these results, which suggest release through RyR2 channels is subject to fast regulation by Ca2+ and Mg2+ followed by time-dependent regulation, to the physiological mechanisms of cardiac channel opening and closing. PMID:12668440

Fission Fragment Mass Distributions and Total Kinetic Energy Release of 235-Uranium and 238-Uranium in Neutron-Induced Fission at Intermediate and Fast Neutron Energies

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

Duke, Dana Lynn

2015-11-12

This Ph.D. dissertation describes a measurement of the change in mass distributions and average total kinetic energy (TKE) release with increasing incident neutron energy for fission of 235U and 238U. Although fission was discovered over seventy-five years ago, open questions remain about the physics of the fission process. The energy of the incident neutron, En, changes the division of energy release in the resulting fission fragments, however, the details of energy partitioning remain ambiguous because the nucleus is a many-body quantum system. Creating a full theoretical model is difficult and experimental data to validate existing models are lacking. Additional fissionmore » measurements will lead to higher-quality models of the fission process, therefore improving applications such as the development of next-generation nuclear reactors and defense. This work also paves the way for precision experiments such as the Time Projection Chamber (TPC) for fission cross section measurements and the Spectrometer for Ion Determination in Fission (SPIDER) for precision mass yields.« less

Signal mass and Ca²⁺ kinetics in local calcium events: a modeling study.

PubMed

Baran, Irina; Ganea, Constanta; Ungureanu, Raluca; Tofolean, Ioana Teodora

2012-02-01

We use a detailed modeling formalism based on numerical simulations of local calcium release events where the blurring of the image, the presence of diffusional barriers provided by large organelles situated close to the release site, as well as the variable position of the scan line with respect to the release site are taken into consideration. We have investigated the effect of the fluorescence noise fluctuations on the accuracy in computing the signal mass from linescan recordings and obtained a quantitative description of both the signal mass and the local increase in the free Ca(2+) level as a function of the release current, the release duration and the orientation of the scan line, for three different levels of noise magnitudes. The model could provide a very good fit to a wide set of available experimental data regarding the signal mass of puffs visualized by fluorescence microscopy in the Xenopus oocyte loaded with 40 μM Oregon Green-1 in the absence of the calcium chelator EGTA. Numerical simulations also predict the amplitude and the kinetics of calcium signals evolving in the absence of the indicator, and indicate that sub-maximal activation of IP(3) receptors could produce in average levels of about 2 μM and 0.4 μM free Ca(2+) close to a release site located in the animal or in the vegetal hemisphere, respectively, whereas the maximal levels reached in more rare events could be 11 μM and 4 μM, respectively.

Encapsulation of methotrexate loaded magnetic microcapsules for magnetic drug targeting and controlled drug release

NASA Astrophysics Data System (ADS)

Chakkarapani, Prabu; Subbiah, Latha; Palanisamy, Selvamani; Bibiana, Arputha; Ahrentorp, Fredrik; Jonasson, Christian; Johansson, Christer

2015-04-01

We report on the development and evaluation of methotrexate magnetic microcapsules (MMC) for targeted rheumatoid arthritis therapy. Methotrexate was loaded into CaCO3-PSS (poly (sodium 4-styrenesulfonate)) doped microparticles that were coated successively with poly (allylamine hydrochloride) and poly (sodium 4-styrenesulfonate) by layer-by-layer technique. Ferrofluid was incorporated between the polyelectrolyte layers. CaCO3-PSS core was etched by incubation with EDTA yielding spherical MMC. The MMC were evaluated for various physicochemical, pharmaceutical parameters and magnetic properties. Surface morphology, crystallinity, particle size, zeta potential, encapsulation efficiency, loading capacity, drug release pattern, release kinetics and AC susceptibility studies revealed spherical particles of ~3 μm size were obtained with a net zeta potential of +24.5 mV, 56% encapsulation and 18.6% drug loading capacity, 96% of cumulative drug release obeyed Hixson-Crowell model release kinetics. Drug excipient interaction, surface area, thermal and storage stability studies for the prepared MMC was also evaluated. The developed MMC offer a promising mode of targeted and sustained release drug delivery for rheumatoid arthritis therapy.

Rapid Retinal Release from a Cone Visual Pigment Following Photoactivation*

PubMed Central

Chen, Min-Hsuan; Kuemmel, Colleen; Birge, Robert R.; Knox, Barry E.

2012-01-01

As part of the visual cycle, the retinal chromophore in both rod and cone visual pigments undergoes reversible Schiff base hydrolysis and dissociation following photobleaching. We characterized light-activated retinal release from a short-wavelength sensitive cone pigment (VCOP) in 0.1% dodecyl maltoside using fluorescence spectroscopy. The half-time (t1/2) of retinal release from VCOP was 7.1 s, 250-fold faster than rhodopsin. VCOP exhibited pH-dependent release kinetics, with the t1/2 decreasing from 23 s to 4 s with pH 4.1 to 8, respectively. However, the Arrhenius activation energy (Ea) for VCOP derived from kinetic measurements between 4° and 20°C was 17.4 kcal/mol, similar to 18.5 kcal/mol for rhodopsin. There was a small kinetic isotope (D2O) effect in VCOP, but less than that observed in rhodopsin. Mutation of the primary Schiff base counterion (VCOPD108A) produced a pigment with an unprotonated chromophore (⌊max = 360 nm) and dramatically slowed (t1/2 ~ 6.8 min) light-dependent retinal release. Using homology modeling, a VCOP mutant with two substitutions (S85D/ D108A) was designed to move the counterion one alpha helical turn into the transmembrane region from the native position. This double mutant had a UV-visible absorption spectrum consistent with a protonated Schiff base (⌊max = 420 nm). Moreover, VCOPS85D/D108A mutant had retinal release kinetics (t1/2 = 7 s) and Ea (18 kcal/mol) similar to the native pigment exhibiting no pH-dependence. By contrast, the single mutant VCOPS85D had a ~3-fold decrease in retinal release rate compared to the native pigment. Photoactivated VCOPD108A had kinetics comparable to a rhodopsin counterion mutant, RhoE113Q, both requiring hydroxylamine to fully release retinal. These results demonstrate that the primary counterion of cone visual pigments is necessary for efficient Schiff base hydrolysis. We discuss how the large differences in retinal release rates between rod and cone visual pigments arise, not from inherent differences in the rate of Schiff base hydrolysis, but rather from differences in the non-covalent binding properties of the retinal chromophore to the protein. PMID:22217337

Shift in Mass Transfer of Wastewater Contaminants from Microplastics in the Presence of Dissolved Substances.

PubMed

Seidensticker, Sven; Zarfl, Christiane; Cirpka, Olaf A; Fellenberg, Greta; Grathwohl, Peter

2017-11-07

In aqueous environments, hydrophobic organic contaminants are often associated with particles. Besides natural particles, microplastics have raised public concern. The release of pollutants from such particles depends on mass transfer, either in an aqueous boundary layer or by intraparticle diffusion. Which of these mechanisms controls the mass-transfer kinetics depends on partition coefficients, particle size, boundary conditions, and time. We have developed a semianalytical model accounting for both processes and performed batch experiments on the desorption kinetics of typical wastewater pollutants (phenanthrene, tonalide, and benzophenone) at different dissolved-organic-matter concentrations, which change the overall partitioning between microplastics and water. Initially, mass transfer is externally dominated, while finally, intraparticle diffusion controls release kinetics. Under boundary conditions typical for batch experiments (finite bath), desorption accelerates with increasing partition coefficients for intraparticle diffusion, while it becomes independent of partition coefficients if film diffusion prevails. On the contrary, under field conditions (infinite bath), the pollutant release controlled by intraparticle diffusion is not affected by partitioning of the compound while external mass transfer slows down with increasing sorption. Our results clearly demonstrate that sorption/desorption time scales observed in batch experiments may not be transferred to field conditions without an appropriate model accounting for both the mass-transfer mechanisms and the specific boundary conditions at hand.

Encapsulation of Naproxen in Lipid-Based Matrix Microspheres: Characterization and Release Kinetics

PubMed Central

Bhoyar, PK; Morani, DO; Biyani, DM; Umekar, MJ; Mahure, JG; Amgaonkar, YM

2011-01-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix. PMID:21731354

Encapsulation of naproxen in lipid-based matrix microspheres: characterization and release kinetics.

PubMed

Bhoyar, P K; Morani, D O; Biyani, D M; Umekar, M J; Mahure, J G; Amgaonkar, Y M

2011-04-01

The objective of this study was to microencapsulate the anti-inflammatory drug (naproxen) to provide controlled release and minimizing or eliminating local side effect by avoiding the drug release in the upper gastrointestinal track. Naproxen was microencapsulated with lipid-like carnauba wax, hydrogenated castor oil using modified melt dispersion (modified congealable disperse phase encapsulation) technique. Effect of various formulation and process variables such as drug-lipid ratio, concentration of modifier, concentration of dispersant, stirring speed, stirring time, temperature of external phase, on evaluatory parameters such as size, entrapment efficiency, and in vitro release of naproxen were studied. The microspheres were characterized for particle size, scanning electron microscopy (SEM), FT-IR spectroscopy, drug entrapment efficiency, in vitro release studies, for in vitro release kinetics. The shape of microspheres was found to be spherical by SEM. The drug entrapment efficiency of various batches of microspheres was found to be ranging from 60 to 90 %w/w. In vitro drug release studies were carried out up to 24 h in pH 7.4 phosphate buffer showing 50-65% drug release. In vitro drug release from all the batches showed better fitting with the Korsmeyer-Peppas model, indicating the possible mechanism of drug release to be by diffusion and erosion of the lipid matrix.

Soft-Template-Synthesized Mesoporous Carbon for Oral Drug Delivery

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

Saha, Dipendu; Warren, Kaitlyn E; Naskar, Amit K

Template-synthesized mesoporous carbons were successfully used in in vitro investigations of controlled delivery of three model drugs, captopril, furosemide, and ranitidine hydrochloride. Captopril and furosemide exhibited desorption kinetics over 30 40 h, and ranitidine HCl had a complete release time of 5 10 h. As evident from the slow release kinetics, we contend that our mesoporous carbon is an improved drug-delivery medium compared to state-of-the-art porous silica-based substrates. The mesoporous carbons, synthesized from phloroglucinol and lignin, a synthetic and a sustainable precursor, respectively, exhibit BET surface area of 200 400 m2 g-1 and pore volume of 0.2 0.6 cm3 g-1.more » The phloroglucinol-based carbon has narrower pore widths and higher pore volume than the lignin-derived counterpart and maintains a longer release time. Numerical modeling of the release kinetics data reveals that the diffusivities of all the drugs from lignin-based carbon media are of equivalent magnitude (10-22 to 10-24 m2 s-1). However, a tailored reduction of pore width in the sorbent reduces the diffusivity of smaller drug molecules (captopril) by an order of magnitude. Thus, engineered pore morphology in our synthesized carbon sorbent, along with its potential to tailor the chemistry of its interaction with sorbet, can be exploited for optimal delivery system of a preferred drug within its therapeutic level and below the level of toxicity.« less

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

Mehl, M; Kukkadapu, G; Kumar, K

The use of gasoline in homogeneous charge compression ignition engines (HCCI) and in duel fuel diesel - gasoline engines, has increased the need to understand its compression ignition processes under engine-like conditions. These processes need to be studied under well-controlled conditions in order to quantify low temperature heat release and to provide fundamental validation data for chemical kinetic models. With this in mind, an experimental campaign has been undertaken in a rapid compression machine (RCM) to measure the ignition of gasoline mixtures over a wide range of compression temperatures and for different compression pressures. By measuring the pressure history duringmore » ignition, information on the first stage ignition (when observed) and second stage ignition are captured along with information on the phasing of the heat release. Heat release processes during ignition are important because gasoline is known to exhibit low temperature heat release, intermediate temperature heat release and high temperature heat release. In an HCCI engine, the occurrence of low-temperature and intermediate-temperature heat release can be exploited to obtain higher load operation and has become a topic of much interest for engine researchers. Consequently, it is important to understand these processes under well-controlled conditions. A four-component gasoline surrogate model (including n-heptane, iso-octane, toluene, and 2-pentene) has been developed to simulate real gasolines. An appropriate surrogate mixture of the four components has been developed to simulate the specific gasoline used in the RCM experiments. This chemical kinetic surrogate model was then used to simulate the RCM experimental results for real gasoline. The experimental and modeling results covered ultra-lean to stoichiometric mixtures, compressed temperatures of 640-950 K, and compression pressures of 20 and 40 bar. The agreement between the experiments and model is encouraging in terms of first-stage (when observed) and second-stage ignition delay times and of heat release rate. The experimental and computational results are used to gain insight into low and intermediate temperature processes during gasoline ignition.« less

Mechanism and kinetics of the loss of poorly soluble drugs from liposomal carriers studied by a novel flow field-flow fractionation-based drug release-/transfer-assay.

PubMed

Hinna, Askell Hvid; Hupfeld, Stefan; Kuntsche, Judith; Bauer-Brandl, Annette; Brandl, Martin

2016-06-28

Liposomes represent a versatile drug formulation approach e.g. for improving the water-solubility of poorly soluble drugs but also to achieve drug targeting and controlled release. For the latter applications it is essential that the drug remains associated with the liposomal carrier during transit in the vascular bed. A range of in vitro test methods has been suggested over the years for prediction of the release of drug from liposomal carriers. The majority of these fail to give a realistic prediction for poorly water-soluble drugs due to the intrinsic tendency of such compounds to remain associated with liposome bilayers even upon extensive dilution. Upon i.v. injection, in contrast, rapid drug loss often occurs due to drug transfer from the liposomal carriers to endogenous lipophilic sinks such as lipoproteins, plasma proteins or membranes of red blood cells and endothelial cells. Here we report on the application of a recently introduced in vitro predictive drug transfer assay based on incubation of the liposomal drug carrier with large multilamellar liposomes, the latter serving as a biomimetic model sink, using flow field-flow fractionation as a tool to separate the two types of liposomes. By quantifying the amount of drug remaining associated with the liposomal drug carrier as well as that transferred to the acceptor liposomes at distinct times of incubation, both the kinetics of drug transfer and release to the water phase could be established for the model drug p-THPP (5,10,15,20-tetrakis(4-hydroxyphenyl)21H,23H-porphine). p-THPP is structurally similar to temoporfin, a photosensitizer which is under clinical evaluation in a liposomal formulation. Mechanistic insights were gained by varying the donor-to-acceptor lipid mass ratio, size and lamellarity of the liposomes. Drug transfer kinetics from one liposome to another was found rate determining as compared to redistribution from the outermost to the inner concentric bilayers, such that the overall process could be adequately described by a single 1st order kinetic model. By varying the donor-to-acceptor lipid mass ratio in the range 1:1 to 1:10, a correlation was established between donor-to-acceptor-lipid mass ratio and transfer kinetics, which is regarded essential for scaling to physiological lipid mass ratios. By applying the assay to a series of structurally related model compounds of different bilayer affinity, transfer and release kinetics were established over the whole expected range of liposome bilayer associated drugs in terms of water solubility and lipophilicity. A very rapid transfer and considerable release from liposomes to the water phase was observed for the more water-soluble compounds Sudan II (clogP 5.45) and Sudan III (clogP 6.83). For the more lipophilic compounds, the rate of transfer from the donor liposomes followed the rank order Sudan IV (fastest)>Oil Red O>Sudan Black>p-THPP (slowest). For an equimolar donor-to-acceptor lipid mass ratio, half-lifes of transfer in the range of 12min (Sudan IV) up to 1.5h (p-THPP) were determined. In essence, the results presented here allow for both, mechanistic insights and predictions of drug loss from liposomal carriers upon exposure to biological sinks, which appear more realistic than the commonly employed in vitro release tests. Copyright © 2016 Elsevier B.V. All rights reserved.

Release kinetics of esterified p-coumaric acid and ferulic acid from rice straw in mild alkaline solution.

PubMed

Linh, Tran Ngoc; Fujita, Hirokata; Sakoda, Akiyoshi

2017-05-01

The release kinetics of esterified p-coumaric acid (PCA) and ferulic acid (FA) from rice straw under a mild alkaline condition were investigated to collect fundamental data for the design of a recovery process. The results showed that the straw size, NaOH concentration, and temperature were the key parameters governing release kinetics. The analysis demonstrated that FA is released considerably faster than PCA. The close relationship between lignin and the PCA dissolution indicates a reciprocal and/or simultaneous release. Moreover, PCA is broadly distributed in the lignin network but tends to be located more densely in the lignin fraction which is not easily solubilized by alkaline treatment. In contrast, the release of FA is strongly affected by removal of lignin fraction which is easily solubilized. These results suggest that the release kinetics are controlled by the accessibility of NaOH to their ester sites in the lignin/hemicellulose network, and by their localization. Copyright © 2017 Elsevier Ltd. All rights reserved.

Intestinal Targeting of Ganciclovir Release Employing a Novel HEC-PAA Blended Lyomatrix.

PubMed

Mabrouk, Mostafa; Mulla, Jameel A S; Kumar, Pradeep; Chejara, Dharmesh R; Badhe, Ravindra V; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-10-01

A hydroxyethylcellulose-poly(acrylic acid) (HEC-PAA) lyomatrix was developed for ganciclovir (GCV) intestine targeting to overcome its undesirable degradation in the stomach. GCV was encapsulated within the HEC-PAA lyomatrix prepared by lyophilization. Conventional tablets were also prepared with identical GCV concentrations in order to compare the GCV release behavior from the lyomatrix and tablets. GCV incorporation (75.12%) was confirmed using FTIR, DSC, and TGA. The effect of GCV loading on the microstructure properties of the lyomatrix was evaluated by SEM, AFM, and BET surface area measurements. The in vitro drug release study showed steady and rapid release profiles from the GCV-loaded lyomatrix compared with the tablet formulation at identical pH values. Minimum GCV release was observed at acidic pH (≤40%) and maximum release occurred at intestinal pH values (≥90%) proving the intestinal targeting ability of the lyomatrix. Kinetic modeling revealed that the GCV-loaded lyomatrix exhibited zero-order release kinetics (n = 1), while the tablets were best described via the Peppas model. Textural analysis highlighted enhanced matrix resilience and rigidity gradient (12.5%, 20 Pa) for the GCV-loaded lyomatrix compared to the pure (7%, 9.5 Pa) HEC-PAA lyomatrix. Bench-top MRI imaging was used to confirm the mechanism of GCV release behavior by monitoring the swelling and erosion rates. The swelling and erosion rate of the tablets was not sufficient to achieve rapid zero-order GCV release as with the lyomatrix. These combined results suggest that the HEC-PAA lyomatrix may be suitable for GCV intestinal targeting after oral administration.

Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid with D-phenylalanine for colon specific drug delivery in inflammatory bowel disease.

PubMed

Dhaneshwar, Suneela S; Gairola, Neha; Kandpal, Mini; Bhatt, Lokesh; Vadnerkar, Gaurav; Kadam, S S

2007-04-01

Mutual azo prodrug of 5-aminosalicylic acid with d-phenylalanine was synthesized by coupling D-phenylalanine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure of synthesized prodrug was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-aminosalicylic acid, whereas in phosphate buffer (pH 7.4) only 15% release was observed over a period of 7h. In rat fecal matter the release of 5-aminosalicylic acid was almost complete (85%), with a half-life of 160.1 min, following first order kinetics. The azo conjugate was evaluated for its ulcerogenic potential by Rainsford's cold stress method. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. The synthesized prodrug was found to be equally effective in mitigating the colitis in rats as that of sulfasalazine without the ulcerogenicity of 5-aminosalicylic acid.

Nanoporous anodic titanium dioxide layers as potential drug delivery systems: Drug release kinetics and mechanism.

PubMed

Jarosz, Magdalena; Pawlik, Anna; Szuwarzyński, Michał; Jaskuła, Marian; Sulka, Grzegorz D

2016-07-01

Nanoporous anodic titanium dioxide (ATO) layers on Ti foil were prepared via a three step anodization process in an electrolyte based on an ethylene glycol solution with fluoride ions. Some of the ATO samples were heat-treated in order to achieve two different crystallographic structures - anatase (400°C) and a mixture of anatase and rutile (600°C). The structural and morphological characterizations of ATO layers were performed using a field emission scanning electron microscope (SEM). The hydrophilicity of ATO layers was determined with contact angle measurements using distilled water. Ibuprofen and gentamicin were loaded effectively inside the ATO nanopores. Afterwards, an in vitro drug release was conducted for 24h under a static and dynamic flow conditions in a phosphate buffer solution at 37°C. The drug concentrations were determined using UV-Vis spectrophotometry. The absorbance of ibuprofen was measured directly at 222nm, whether gentamicin was determined as a complex with silver nanoparticles (Ag NPs) at 394nm. Both compounds exhibited long term release profiles, despite the ATO structure. A new release model, based on the desorption of the drug from the ATO top surface followed by the desorption and diffusion of the drug from the nanopores, was derived. The proposed release model was fitted to the experimental drug release profiles, and kinetic parameters were calculated. Copyright © 2016 Elsevier B.V. All rights reserved.

In silico study on the effects of matrix structure in controlled drug release

NASA Astrophysics Data System (ADS)

Villalobos, Rafael; Cordero, Salomón; Maria Vidales, Ana; Domínguez, Armando

2006-07-01

Purpose: To study the effects of drug concentration and spatial distribution of the medicament, in porous solid dosage forms, on the kinetics and total yield of drug release. Methods: Cubic networks are used as models of drug release systems. They were constructed by means of the dual site-bond model framework, which allows a substrate to have adequate geometrical and topological distribution of its pore elements. Drug particles can move inside the networks by following a random walk model with excluded volume interactions between the particles. The drug release time evolution for different drug concentration and different initial drug spatial distribution has been monitored. Results: The numerical results show that in all the studied cases, drug release presents an anomalous behavior, and the consequences of the matrix structural properties, i.e., drug spatial distribution and drug concentration, on the drug release profile have been quantified. Conclusions: The Weibull function provides a simple connection between the model parameters and the microstructure of the drug release device. A critical modeling of drug release from matrix-type delivery systems is important in order to understand the transport mechanisms that are implicated, and to predict the effect of the device design parameters on the release rate.

Hindered disulfide bonds to regulate release rate of model drug from mesoporous silica.

PubMed

Nadrah, Peter; Maver, Uroš; Jemec, Anita; Tišler, Tatjana; Bele, Marjan; Dražić, Goran; Benčina, Mojca; Pintar, Albin; Planinšek, Odon; Gaberšček, Miran

2013-05-01

With the advancement of drug delivery systems based on mesoporous silica nanoparticles (MSNs), a simple and efficient method regulating the drug release kinetics is needed. We developed redox-responsive release systems with three levels of hindrance around the disulfide bond. A model drug (rhodamine B dye) was loaded into MSNs' mesoporous voids. The pore opening was capped with β-cyclodextrin in order to prevent leakage of drug. Indeed, in absence of a reducing agent the systems exhibited little leakage, while the addition of dithiothreitol cleaved the disulfide bonds and enabled the release of cargo. The release rate and the amount of released dye were tuned by the level of hindrance around disulfide bonds, with the increased hindrance causing a decrease in the release rate as well as in the amount of released drug. Thus, we demonstrated the ability of the present mesoporous systems to intrinsically control the release rate and the amount of the released cargo by only minor structural variations. Furthermore, an in vivo experiment on zebrafish confirmed that the present model delivery system is nonteratogenic.

Local CFD kinetic model of cadmium vaporization during fluid bed incineration of municipal solid waste.

PubMed

Soria, J; Gauthier, D; Falcoz, Q; Flamant, G; Mazza, G

2013-03-15

The emissions of heavy metals during incineration of Municipal Solid Waste (MSW) are a major issue to health and the environment. It is then necessary to well quantify these emissions in order to accomplish an adequate control and prevent the heavy metals from leaving the stacks. In this study the kinetic behavior of Cadmium during Fluidized Bed Incineration (FBI) of artificial MSW pellets, for bed temperatures ranging from 923 to 1073 K, was modeled. FLUENT 12.1.4 was used as the modeling framework for the simulations and implemented together with a complete set of user-defined functions (UDFs). The CFD model combines the combustion of a single solid waste particle with heavy metal (HM) vaporization from the burning particle, and it takes also into account both pyrolysis and volatiles' combustion. A kinetic rate law for the Cd release, derived from the CFD thermal analysis of the combusting particle, is proposed. The simulation results are compared with experimental data obtained in a lab-scale fluidized bed incinerator reported in literature, and with the predicted values from a particulate non-isothermal model, formerly developed by the authors. The comparison shows that the proposed CFD model represents very well the evolution of the HM release for the considered range of bed temperature. Copyright © 2013 Elsevier B.V. All rights reserved.

Kinetics of devolatilization and oxidation of a pulverized biomass in an entrained flow reactor under realistic combustion conditions

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

Jimenez, Santiago; Remacha, Pilar; Ballester, Javier

2008-03-15

In this paper the results of a complete set of devolatilization and combustion experiments performed with pulverized ({proportional_to}500 {mu}m) biomass in an entrained flow reactor under realistic combustion conditions are presented. The data obtained are used to derive the kinetic parameters that best fit the observed behaviors, according to a simple model of particle combustion (one-step devolatilization, apparent oxidation kinetics, thermally thin particles). The model is found to adequately reproduce the experimental trends regarding both volatile release and char oxidation rates for the range of particle sizes and combustion conditions explored. The experimental and numerical procedures, similar to those recentlymore » proposed for the combustion of pulverized coal [J. Ballester, S. Jimenez, Combust. Flame 142 (2005) 210-222], have been designed to derive the parameters required for the analysis of biomass combustion in practical pulverized fuel configurations and allow a reliable characterization of any finely pulverized biomass. Additionally, the results of a limited study on the release rate of nitrogen from the biomass particle along combustion are shown. (author)« less

Fire Suppression M and S Validation (Status and Challenges), Systems Fire Protection Information Exchange

DTIC Science & Technology

2015-10-14

rate Kinetics •14 Species & 12 reactionsCombustion Model •Participating Media Discrete Ordinate Method •WSG model for CO2, H2O and SootRadiation Model...Inhibition of JP-8 Combustion Physical Acting Agents • Dilute heat • Dilute reactants Ex: water, nitrogen Chemical Acting Agents • Reduce flame...Release; distribution is unlimited 5 Overview of Reduced Kinetics Scheme for FM200 • R1: JP-8 + O2 => CO + CO2 + H2O • R2: CO + O2 <=> CO2 • R3: HFP + JP-8

Chemistry Resolved Kinetic Flow Modeling of TATB Based Explosives

NASA Astrophysics Data System (ADS)

Vitello, Peter; Fried, Lawrence; Howard, Mike; Levesque, George; Souers, Clark

2011-06-01

Detonation waves in insensitive, TATB based explosives are believed to have multi-time scale regimes. The initial burn rate of such explosives has a sub-microsecond time scale. However, significant late-time slow release in energy is believed to occur due to diffusion limited growth of carbon. In the intermediate time scale concentrations of product species likely change from being in equilibrium to being kinetic rate controlled. We use the thermo-chemical code CHEETAH linked to ALE hydrodynamics codes to model detonations. We term our model chemistry resolved kinetic flow as CHEETAH tracks the time dependent concentrations of individual species in the detonation wave and calculate EOS values based on the concentrations. A validation suite of model simulations compared to recent high fidelity metal push experiments at ambient and cold temperatures has been developed. We present here a study of multi-time scale kinetic rate effects for these experiments. Prepared by LLNL under Contract DE-AC52-07NA27344.

Nanomedicines for Inflammatory Arthritis: Head-To-Head Comparison of Glucocorticoid-Containing Polymers, Micelles and Liposomes

PubMed Central

Crielaard, Bart J.; Dusad, Anand; Lele, Subodh M.; Rijcken, Cristianne J. F.; Metselaar, Josbert M; Kostková, Hana; Etrych, Tomáš; Ulbrich, Karel; Kiessling, Fabian; Mikuls, Ted R.; Hennink, Wim E.; Storm, Gert; Lammers, Twan; Wang, Dong

2014-01-01

As an emerging research direction, nanomedicine has been increasingly utilized to treat inflammatory diseases. In this head-to-head comparison study, four established nanomedicine formulations of dexamethasone, including liposomes (L-Dex), core-crosslinked micelles (M-Dex), slow releasing polymeric prodrugs (P-Dex-slow) and fast releasing polymeric prodrugs (P-Dex-fast), were evaluated in an adjuvant-induced arthritis rat model with an equivalent dose treatment design. It was found that after a single i.v. injection, the formulations with the slower drug release kinetics (i.e. M-Dex and P-Dex-slow) maintained longer duration of therapeutic activity than those with relatively faster drug release kinetics, resulting in better joint protection. This finding will be instructional in the future development and optimization of nanomedicines for the clinical management of rheumatoid arthritis. The outcome of this study also illustrates the value of such head-to-head comparison studies in translational nanomedicine research. PMID:24341611

Comminution of solids caused by kinetic energy of high shear strain rate, with implications for impact, shock, and shale fracturing.

PubMed

Bazant, Zdenek P; Caner, Ferhun C

2013-11-26

Although there exists a vast literature on the dynamic comminution or fragmentation of rocks, concrete, metals, and ceramics, none of the known models suffices for macroscopic dynamic finite element analysis. This paper outlines the basic idea of the macroscopic model. Unlike static fracture, in which the driving force is the release of strain energy, here the essential idea is that the driving force of comminution under high-rate compression is the release of the local kinetic energy of shear strain rate. The density of this energy at strain rates >1,000/s is found to exceed the maximum possible strain energy density by orders of magnitude, making the strain energy irrelevant. It is shown that particle size is proportional to the -2/3 power of the shear strain rate and the 2/3 power of the interface fracture energy or interface shear stress, and that the comminution process is macroscopically equivalent to an apparent shear viscosity that is proportional (at constant interface stress) to the -1/3 power of this rate. A dimensionless indicator of the comminution intensity is formulated. The theory was inspired by noting that the local kinetic energy of shear strain rate plays a role analogous to the local kinetic energy of eddies in turbulent flow.

Chemistry resolved kinetic flow modeling of TATB based explosives

NASA Astrophysics Data System (ADS)

Vitello, Peter; Fried, Laurence E.; William, Howard; Levesque, George; Souers, P. Clark

2012-03-01

Detonation waves in insensitive, TATB-based explosives are believed to have multiple time scale regimes. The initial burn rate of such explosives has a sub-microsecond time scale. However, significant late-time slow release in energy is believed to occur due to diffusion limited growth of carbon. In the intermediate time scale concentrations of product species likely change from being in equilibrium to being kinetic rate controlled. We use the thermo-chemical code CHEETAH linked to an ALE hydrodynamics code to model detonations. We term our model chemistry resolved kinetic flow, since CHEETAH tracks the time dependent concentrations of individual species in the detonation wave and calculates EOS values based on the concentrations. We present here two variants of our new rate model and comparison with hot, ambient, and cold experimental data for PBX 9502.

Enantioselectively controlled release of chiral drug (metoprolol) using chiral mesoporous silica materials

NASA Astrophysics Data System (ADS)

Guo, Zhen; Du, Yu; Liu, Xianbin; Ng, Siu-Choon; Chen, Yuan; Yang, Yanhui

2010-04-01

Chiral porous materials have attracted burgeoning attention on account of their potential applications in many areas, such as enantioseparation, chiral catalysis, chemical sensors and drug delivery. In this report, chiral mesoporous silica (CMS) materials with various pore sizes and structures were prepared using conventional achiral templates (other than chiral surfactant) and a chiral cobalt complex as co-template. The synthesized CMS materials were characterized by x-ray diffraction, nitrogen physisorption, scanning electron microscope and transmission electron microscope. These CMS materials, as carriers, were demonstrated to be able to control the enantioselective release of a representative chiral drug (metoprolol). The release kinetics, as modeled by the power law equation, suggested that the release profiles of metoprolol were remarkably dependent on the pore diameter and pore structure of CMS materials. More importantly, R- and S-enantiomers of metoprolol exhibited different release kinetics on CMS compared to the corresponding achiral mesoporous silica (ACMS), attributable to the existence of local chirality on the pore wall surface of CMS materials. The chirality of CMS materials on a molecular level was further substantiated by vibrational circular dichroism measurements.

Modulating release of ranibizumab and aflibercept from thiolated chitosan-based hydrogels for potential treatment of ocular neovascularization.

PubMed

Moreno, Miguel; Pow, Poh Yih; Tabitha, Tan Su Teng; Nirmal, Sonali; Larsson, Andreas; Radhakrishnan, Krishna; Nirmal, Jayabalan; Quah, Soo Tng; Geifman Shochat, Susana; Agrawal, Rupesh; Venkatraman, Subbu

2017-08-01

This paper describes the synthesis of thiolated chitosan-based hydrogels with varying degrees of crosslinking that has been utilized to modulate release kinetics of two clinically relevant FDA-approved anti-VEGF protein drugs, ranibizumab and aflibercept. These hydrogels have been fabricated into disc shaped structures for potential use as patches on ocular surface. Protein conformational changes and aggregation after loading and release was evaluated by circular dichroism (CD), steady-state tryptophan fluorescence spectroscopy, electrophoresis and size-exclusion chromatography (SEC). Finally, the capacity of both released proteins to bind to VEGF was tested by ELISA and surface plasmon resonance (SPR) technology. The study demonstrates the versatility of thiolated chitosan-based hydrogels for delivering proteins. The effect of various parameters of the hydrogel on protein release kinetics and mechanism of protein release was studied using the Korsmeyer-Peppas release model. Furthermore, we have studied the stability of released proteins in detail while comparing it with non-entrapped proteins under physiological conditions to understand the effect of formulation conditions on protein stability. The disc-shaped thiolated chitosan-based hydrogels provide a potentially useful platform to deliver ranibizumab and aflibercept for the treatments of ocular diseases such as wet AMD, DME and corneal neovascularization.

Pathways of proton release in the bacteriorhodopsin photocycle

NASA Technical Reports Server (NTRS)

Zimanyi, L.; Varo, G.; Chang, M.; Ni, B.; Needleman, R.; Lanyi, J. K.

1992-01-01

The pH dependencies of the rate constants in the photocycles of recombinant D96N and D115N/D96N bacteriorhodopsins were determined from time-resolved difference spectra between 70 ns and 420 ms after photoexcitation. The results were consistent with the model suggested earlier for proteins containing D96N substitution: BR hv----K----L----M1----M2----BR. Only the M2----M1 back-reaction was pH-dependent: its rate increased with increasing [H+] between pH 5 and 8. We conclude from quantitative analysis of this pH dependency that its reverse, the M1----M2 reaction, is linked to the release of a proton from a group with a pKa = 5.8. This suggests a model for wild-type bacteriorhodopsin in which at pH greater than 5.8 the transported proton is released on the extracellular side from this as yet unknown group and on the 100-microseconds time scale, but at pH less than 5.8, the proton release occurs from another residue and later in the photocycle most likely directly from D85 during the O----BR reaction. We postulate, on the other hand, that proton uptake on the cytoplasmic side will be by D96 and during the N----O reaction regardless of pH. The proton kinetics as measured with indicator dyes confirmed the unique prediction of this model: at pH greater than 6, proton release preceded proton uptake, but at pH less than 6, the release was delayed until after the uptake. The results indicated further that the overall M1----M2 reaction includes a second kinetic step in addition to proton release; this is probably the earlier postulated extracellular-to-cytoplasmic reorientation switch in the proton pump.

Synthesis and evaluation of chondroitin sulfate based hydrogels of loxoprofen with adjustable properties as controlled release carriers.

PubMed

Khalid, Ikrima; Ahmad, Mahmood; Usman Minhas, Muhammad; Barkat, Kashif

2018-02-01

Mixtures of polymer (chondroitin sulfate) and monomer (AMPS) in the presence of co-monomer (MBA) were employed for the production of hydrogels, with adjustable properties, following free radical copolymerization. The hydrogel's structural properties were assessed by FTIR, DSC, TGA, SEM and XRD which confirmed the development and stability of synthesized structure. The results from FTIR analysis showed that CS react with the AMPS monomer during the polymerization process and confirmed the grafting of AMPS chains onto CS backbone. The surface morphology of CS-co-poly(AMPS) hydrogels, as evident by SEM, corresponds to their improved swelling ability due to high porosity. Thermal analysis showed that crosslinking formed a stable hydrogel network which is thermally more stable than its basic ingredients. The effects of pH revealed an increasing trend in swelling with increasing concentration of either CS or AMPS. In addition, different modalities for drug loading were studied with respect to drug homogeneous distribution; loxoprofen sodium was employed as model drug and was loaded by swelling-diffusion method. In vitro drug release profiles and kinetics were assessed to confirm their reproducibility and reliability. Higuchi model is the best fit model to explain drug release from formed gels indicating diffusion-controlled release. Similarly, Korsmeyer-Peppas model yields remarkably good adjustments where release kinetics involves a combination of diffusion in hydrated matrix and polymer relaxation. Conclusively, CS-co-poly(AMPS) hydrogels could be a potential alternate to conventional dosage forms for controlled delivery of loxoprofen sodium for extended period of time. Copyright © 2017. Published by Elsevier Ltd.

On-Line Analysis and Kinetic Behavior of Arsenic Release during Coal Combustion and Pyrolysis.

PubMed

Shen, Fenghua; Liu, Jing; Zhang, Zhen; Dai, Jinxin

2015-11-17

The kinetic behavior of arsenic (As) release during coal combustion and pyrolysis in a fluidized bed was investigated by applying an on-line analysis system of trace elements in flue gas. This system, based on inductively coupled plasma optical emission spectroscopy (ICP-OES), was developed to measure trace elements concentrations in flue gas quantitatively and continuously. Obvious variations of arsenic concentration in flue gas were observed during coal combustion and pyrolysis, indicating strong influences of atmosphere and temperature on arsenic release behavior. Kinetic laws governing the arsenic release during coal combustion and pyrolysis were determined based on the results of instantaneous arsenic concentration in flue gas. A second-order kinetic law was determined for arsenic release during coal combustion, and the arsenic release during coal pyrolysis followed a fourth-order kinetic law. The results showed that the arsenic release rate during coal pyrolysis was faster than that during coal combustion. Thermodynamic calculations were carried out to identify the forms of arsenic in vapor and solid phases during coal combustion and pyrolysis, respectively. Ca3(AsO4)2 and Ca(AsO2)2 are the possible species resulting from As-Ca interaction during coal combustion. Ca(AsO2)2 is the most probable species during coal pyrolysis.

Synthesis and characterization of poly(propylene imine)-dendrimer-grafted gold nanoparticles as nanocarriers of doxorubicin.

PubMed

Golshan, Marzieh; Salami-Kalajahi, Mehdi; Mirshekarpour, Mina; Roghani-Mamaqani, Hossein; Mohammadi, Maryam

2017-07-01

The aim of current work is synthesis 4th-generation-poly(propylene imine) (PPI)-dendrimer modified gold nanoparticles (Au-G4A) as nanocarriers for doxorubicin (DOX) and studying in vitro drug release kinetics from nanocarriers into different media. Accordingly, AuNPs were synthesized by reduction of chloroauric acid (HAuCl 4 ) aqueous solution with trisodium citrate and modified with cysteamine to obtain amine-functionalized (Au-NH 2 ) nanoparticles. Au-NH 2 nanoparticles were used as multifunctional cores and participated in Michael addition of acrylonitrile and reduction process by lithium aluminum hydride (LAH) to synthesize Au-G4A nanoparticles. Also, peripheral primary amine groups of Au-G4A were conjugated with folic acid (FA) (Au-G4F) to study the bioconjugation effect on drug release behavior of nanostructures. Ultraviolet spectroscopy (UV-vis), atomic force microscopy (AFM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) were used to approve the synthesis of different nanostructures. Finally, Au-G4A and Au-G4F samples were loaded with DOX and exposed to environments with different pH values to examine the release properties of nanostructures. Also, drug release kinetics was investigated by fitting of experimental data with different release models. As a result, synthesized dendritic structures showed Higuchi and Korsmeyer-Peppas models release behavior due to better solubility of drug in release media with respect to dendrimer cavities and drug release through polymeric matrix respectively. Copyright © 2017 Elsevier B.V. All rights reserved.

A Gas-Kinetic Scheme for Multimaterial Flows and Its Application in Chemical Reaction

NASA Technical Reports Server (NTRS)

Lian, Yongsheng; Xu, Kun

1999-01-01

This paper concerns the extension of the multicomponent gas-kinetic BGK-type scheme to multidimensional chemical reactive flow calculations. In the kinetic model, each component satisfies its individual gas-kinetic BGK equation and the equilibrium states of both components are coupled in space and time due to the momentum and energy exchange in the course of particle collisions. At the same time, according to the chemical reaction rule one component can be changed into another component with the release of energy, where the reactant and product could have different gamma. Many numerical test cases are included in this paper, which show the robustness and accuracy of kinetic approach in the description of multicomponent reactive flows.

The Distribution of Solar Wind Speeds During Solar Minimum: Calibration for Numerical Solar Wind Modeling Constraints on the Source of the Slow Solar Wind (Postprint)

DTIC Science & Technology

2012-03-05

subsonic corona below the critical point, resulting in an increased scale height and mass flux, while keeping the kinetic energy of the flow fairly...Approved for public release; distribution is unlimited. tubes with small expansion factors the heating occurs in the supersonic corona, where the energy ...goes into the kinetic energy of the solar wind, increasing the flow speed [Leer and Holzer, 1980; Pneuman, 1980]. Using this model and a sim- plified

Course 1: Physics of Protein-DNA Interaction

NASA Astrophysics Data System (ADS)

Bruinsma, R. F.

1 Introduction 1.1 The central dogma and bacterial gene expression 1.2 Molecular structure 2 Thermodynamics and kinetics of repressor-DNA interaction 2.1 Thermodynamics and the lac repressor 2.2 Kinetics of repressor-DNA interaction 3 DNA deformability and protein-DNA interaction 3.1 Introduction 3.2 The worm-like chain 3.3 The RST model 4 Electrostatics in water and protein-DNA interaction 4.1 Macro-ions and aqueous electrostatics 4.2 The primitive model 4.3 Manning condensation 4.4 Counter-ion release and non-specific protein-DNA interaction

Chemistry Resolved Kinetic Flow Modeling of TATB Based Explosives

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

Vitello, P A; Fried, L E; Howard, W M

2011-07-21

Detonation waves in insensitive, TATB based explosives are believed to have multi-time scale regimes. The initial burn rate of such explosives has a sub-microsecond time scale. However, significant late-time slow release in energy is believed to occur due to diffusion limited growth of carbon. In the intermediate time scale concentrations of product species likely change from being in equilibrium to being kinetic rate controlled. They use the thermo-chemical code CHEETAH linked to an ALE hydrodynamics code to model detonations. They term their model chemistry resolved kinetic flow as CHEETAH tracks the time dependent concentrations of individual species in the detonationmore » wave and calculates EOS values based on the concentrations. A HE-validation suite of model simulations compared to experiments at ambient, hot, and cold temperatures has been developed. They present here a new rate model and comparison with experimental data.« less

Analysis of transient fission gas behaviour in oxide fuel using BISON and TRANSURANUS

DOE PAGES

Barani, T.; Bruschi, E.; Pizzocri, D.; ...

2017-01-03

The modelling of fission gas behaviour is a crucial aspect of nuclear fuel analysis in view of the related effects on the thermo-mechanical performance of the fuel rod, which can be particularly significant during transients. Experimental observations indicate that substantial fission gas release (FGR) can occur on a small time scale during transients (burst release). To accurately reproduce the rapid kinetics of burst release in fuel performance calculations, a model that accounts for non-diffusional mechanisms such as fuel micro-cracking is needed. In this work, we present and assess a model for transient fission gas behaviour in oxide fuel, which ismore » applied as an extension of diffusion-based models to allow for the burst release effect. The concept and governing equations of the model are presented, and the effect of the newly introduced parameters is evaluated through an analytic sensitivity analysis. Then, the model is assessed for application to integral fuel rod analysis. The approach that we take for model assessment involves implementation in two structurally different fuel performance codes, namely, BISON (multi-dimensional finite element code) and TRANSURANUS (1.5D semi-analytic code). The model is validated against 19 Light Water Reactor fuel rod irradiation experiments from the OECD/NEA IFPE (International Fuel Performance Experiments) database, all of which are simulated with both codes. The results point out an improvement in both the qualitative representation of the FGR kinetics and the quantitative predictions of integral fuel rod FGR, relative to the canonical, purely diffusion-based models, with both codes. The overall quantitative improvement of the FGR predictions in the two codes is comparable. Furthermore, calculated radial profiles of xenon concentration are investigated and compared to experimental data, demonstrating the representation of the underlying mechanisms of burst release by the new model.« less

Modeling the pharmacokinetics of extended release pharmaceutical systems

NASA Astrophysics Data System (ADS)

di Muria, Michela; Lamberti, Gaetano; Titomanlio, Giuseppe

2009-03-01

The pharmacokinetic (PK) models predict the hematic concentration of drugs after the administration. In compartment modeling, the body is described by a set of interconnected “vessels” or “compartments”; the modeling consisting of transient mass balances. Usually the orally administered drugs were considered as immediately available: this cannot describe the administration of extended-release systems. In this work we added to the traditional compartment models the ability to account for a delay in administration, relating this delay to in vitro data. Firstly, the method was validated, applying the model to the dosage of nicotine by chewing-gum; the model was tuned by in vitro/in vivo data of drugs (divalproex-sodium and diltiazem) with medium-rate release kinetics, then it was applied in describing in vivo evolutions due to the assumption of fast- and slow-release systems. The model reveals itself predictive, the same of a Level A in vitro/in vivo correlation, but being physically based, it is preferable to a purely statistical method.

Drug Release Kinetics and Transport Mechanisms of Non-degradable and Degradable Polymeric Delivery Systems

PubMed Central

Fu, Yao; Kao, Weiyuan John

2010-01-01

Importance of the field The advancement in material design and engineering has led to the rapid development of novel materials with increasing complexity and functions. Both non-degradable and degradable polymers have found wide applications in the controlled delivery field. Studies on drug release kinetics provide important information into the function of material systems. To elucidate the detailed transport mechanism and the structure-function relationship of a material system, it is critical to bridge the gap between the macroscopic data and the transport behavior at the molecular level. Areas covered in this review The structure and function information of selected non-degradable and degradable polymers have been collected and summarized from literatures published after 1990s. The release kinetics of selected drug compounds from various material systems will be discussed in case studies. Recent progresses in the mathematical models based on different transport mechanisms will be highlighted. What the reader will gain This article aims to provide an overview of structure-function relationships of selected non-degradable and degradable polymers as drug delivery matrices. Take home message Understanding the structure-function relationship of the material system is key to the successful design of a delivery system for a particular application. Moreover, developing complex polymeric matrices requires more robust mathematical models to elucidate the solute transport mechanisms. PMID:20331353

Selective adsorption of oppositely charged PNIPAAM on halloysite surfaces: a route to thermo-responsive nanocarriers.

PubMed

Cavallaro, Giuseppe; Lazzara, Giuseppe; Lisuzzo, Lorenzo; Milioto, Stefana; Parisi, Filippo

2018-08-10

Halloysite nanotubes were functionalized with stimuli-responsive macromolecules to generate smart nanohybrids. Poly(N-isopropylacrylamide)-co-methacrylic acid (PNIPAAM-co-MA) was selectively adsorbed into halloysite lumen by exploiting electrostatic interactions. Amine-terminated PNIPAAM polymer was also investigated that selectively interacts with the outer surface of the nanotubes. The adsorption site has a profound effect on the thermodynamic behavior and therefore temperature responsive features of the hybrid material. The drug release kinetics was investigated by using diclofenac as a non-steroidal anti-inflammatory drug model. The release kinetics depends on the nanoarchitecture of the PNIPAAM/halloysite based material. In particular, diclofenac release was slowed down above the LCST for PNIPAAM-co-MA/halloysite. Opposite trends occurred for halloysite functionalized with PNIPAAM at the outer surface. This work represents a further step toward the opportunity to extend and control the delivery conditions of active species, which represent a key point in technological applications.

[The release of biologically active compounds from peat peloids].

PubMed

Babaskin, D V

2011-01-01

This work had the objective to study kinetics of the release of flavonoides from peat peloid compositions containing extracts of medicinal herbs in model systems.The key parameters of the process are defined. The rate of liberation of flavonoides is shown to depend on their initial concentration in the compositions being used. The influence of the flavonoide composition of the tested extracts and dimethylsulfoxide on the release of biologically active compounds contained in the starting material in the model environment is estimated. The possibility of the layer-by-layer deposition of the compositions and peat peloids in order to increase the efficacy of flavonoide release from the starting composition and to ensure more rational utilization of the extracts of medicinal plants is demonstrated.

Kinetics of Exocytosis Is Faster in Cones Than in Rods

PubMed Central

Rabl, Katalin; Cadetti, Lucia; Thoreson, Wallace B.

2006-01-01

Cone-driven responses of second-order retinal neurons are considerably faster than rod-driven responses. We examined whether differences in the kinetics of synaptic transmitter release from rods and cones may contribute to differences in postsynaptic response kinetics. Exocytosis from rods and cones was triggered by membrane depolarization and monitored in two ways: (1) by measuring EPSCs evoked in second-order neurons by depolarizing steps applied to presynaptic rods or cones during simultaneous paired whole-cell recordings or (2) by direct measurements of exocytotic increases in membrane capacitance. The kinetics of release was assessed by varying the length of the depolarizing test step. Both measures of release revealed two kinetic components to the increase in exocytosis as a function of the duration of a step depolarization. In addition to slow sustained components in both cell types, the initial fast component of exocytosis had a time constant of <5 ms in cones, >10-fold faster than that of rods. Rod/cone differences in the kinetics of release were substantiated by a linear correlation between depolarization-evoked capacitance increases and EPSC charge transfer. Experiments on isolated rods indicate that the slower kinetics of exocytosis from rods was not a result of rod–rod coupling. The initial rapid release of vesicles from cones can shape the postsynaptic response and may contribute to the faster responses of cone-driven cells observed at light offset. PMID:15872111

Calcium channel dynamics limit synaptic release in response to prosthetic stimulation with sinusoidal waveforms

PubMed Central

Freeman, Daniel K.; Jeng, Jed S.; Kelly, Shawn K.; Hartveit, Espen; Fried, Shelley I.

2011-01-01

Extracellular electric stimulation with sinusoidal waveforms has been shown to allow preferential activation of individual types of retinal neurons by varying stimulus frequency. It is important to understand the mechanisms underlying this frequency dependence as a step towards improving methods of preferential activation. In order to elucidate these mechanisms, we implemented a morphologically realistic model of a retinal bipolar cell and measured the response to extracellular stimulation with sinusoidal waveforms. We compared the frequency response of a passive membrane model to the kinetics of voltage-gated calcium channels that mediate synaptic release. The passive electrical properties of the membrane exhibited lowpass filtering with a relatively high cutoff frequency (nominal value = 717 Hz). This cutoff frequency was dependent on intra-axonal resistance, with shorter and wider axons yielding higher cutoff frequencies. However, we found that the cutoff frequency of bipolar cell synaptic release was primarily limited by the relatively slow opening kinetics of Land T-type calcium channels. The cutoff frequency of calcium currents depended nonlinearly on stimulus amplitude, but remained lower than the cutoff frequency of the passive membrane model for a large range of membrane potential fluctuations. These results suggest that while it may be possible to modulate the membrane potential of bipolar cells over a wide range of stimulus frequencies, synaptic release will only be initiated at the lower end of this range. PMID:21628768

Dynamic release of gentamicin sulfate (GS) from alginate dialdehyde (AD)-crosslinked casein (CAS) films for antimicrobial applications

PubMed Central

Bajpai, S. K.; Shah, Farhan Ferooz; Bajpai, M.

2017-01-01

Abstract In the present work, antibiotic drug gentamicin sulfate (GS) has been loaded into alginate dialdehyde-crosslinked casein (CAS) films for wound dressing applications. The films have been characterized by Fourier transform infrared spectroscopy, X-ray diffraction analysis and scanning electron microscopy. The dynamic release of model drug GS has been investigated in the physiological fluid at 37 °C. The drug release data has been interpreted in the terms of various kinetic models such as Power function model, first order model and Schott model. The release data was found to be well fitted by Schott model. The various diffusion coefficients are also evaluated. The adsorption of model therapeutic protein BSA on the film has been investigated. The maximum adsorption is found to be 5.7 mg/cm2.The films were tested for their antibacterial and anti-fungal action. Finally, the in vivo wound healing study was carried out on Albino wistar rats. PMID:29491776

Dynamic Regulation of Cell Volume and Extracellular ATP of Human Erythrocytes

PubMed Central

Leal Denis, M. Florencia; Alvarez, H. Ariel; Lauri, Natalia; Alvarez, Cora L.; Chara, Osvaldo; Schwarzbaum, Pablo J.

2016-01-01

Introduction The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regulation between Vr and ATPe. Methods and Treatments We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors. Results In rbcs 10 μM MST7 promoted acute, strongly correlated changes in [ATPe] and Vr. Whereas MST7 induced increases of 10% in Vr and 190 nM in [ATPe], blocking swelling in a hyperosmotic medium + MST7 reduced [ATPe] by 40%. Pre-incubation of rbcs with 10 μM of either carbenoxolone or probenecid, two inhibitors of the ATP conduit pannexin 1, reduced [ATPe] by 40–50% and swelling by 40–60%, while in the presence of 80 U/mL apyrase, an ATPe scavenger, cell swelling was prevented. While exposure to 10 μM NF110, a blocker of ATP-P2X receptors mediating sodium influx, reduced [ATPe] by 48%, and swelling by 80%, incubation of cells in sodium free medium reduced swelling by 92%. Analysis and Discussion Results were analyzed by means of a mathematical model where ATPe kinetics and Vr kinetics were mutually regulated. Model dependent fit to experimental data showed that, upon MST7 exposure, ATP efflux required a fast 1960-fold increase of ATP permeability, mediated by two kinetically different conduits, both of which were activated by swelling and inactivated by time. Both experimental and theoretical results suggest that, following MST7 exposure, ATP is released via two conduits, one of which is mediated by pannexin 1. The accumulated ATPe activates P2X receptors, followed by sodium influx, resulting in cell swelling, which in turn further activates ATP release. Thus swelling and P2X receptors constitute essential components of a positive feedback loop underlying ATP-induced ATP release of rbcs. PMID:27355484

Proof-of-concept study on the suitability of 13C-urea as a marker substance for assessment of in vivo behaviour of oral colon-targeted dosage forms

PubMed Central

Schellekens, RCA; Olsder, GG; Langenberg, SMCH; Boer, T; Woerdenbag, HJ; Frijlink, HW; Kosterink, JGW; Stellaard, F

2009-01-01

Background and purpose: 13C-urea may be a suitable marker to assess the in vivo fate of colon-targeted dosage forms given by mouth. We postulated that release in the colon (urease-rich segment) of 13C-urea from colon-targeted capsules would lead to fermentation of 13C-urea by bacterial ureases into 13CO2. Subsequent absorption into the blood and circulation would lead to detectable 13C (as 13CO2) in breath. If, however, release of 13C-urea occurred in the small intestine (urease-poor segment), we expected detectable 13C (as 13C-urea) in blood but no breath 13C (as 13CO2). The differential kinetics of 13C-urea could thus potentially describe both release kinetics and indicate the gastrointestinal segment of release. Experimental approach: The in vivo study consisted of three experiments, during which the same group of four volunteers participated. Key results: The kinetic model was internally valid. The appearance of 13C-in breath CO2 (Ffermented) and the appearance of 13C in blood as 13C-urea (Fnot fermented) show a high inverse correlation (Pearson's r=−0.981, P= 0.06). The total recovery of 13C (Ffermented+Fnot fermented) averaged 99%, indicating complete recovery of the administered 13C via breath and blood. 13CO2 exhalation was observed in all subjects. This indicates that 13C-urea was available in urease-rich segments, such as the caecum or colon. Conclusions and implications: In this proof-of-concept study, 13C-urea was able to provide information on both the release kinetics of a colon-targeted oral dosage form and the gastrointestinal segment where it was released. PMID:19732063

Electrogenic Binding of Intracellular Cations Defines a Kinetic Decision Point in the Transport Cycle of the Human Serotonin Transporter.

PubMed

Hasenhuetl, Peter S; Freissmuth, Michael; Sandtner, Walter

2016-12-09

The plasmalemmal monoamine transporters clear the extracellular space from their cognate substrates and sustain cellular monoamine stores even during neuronal activity. In some instances, however, the transporters enter a substrate-exchange mode, which results in release of intracellular substrate. Understanding what determines the switch between these two transport modes demands time-resolved measurements of intracellular (co-)substrate binding and release. Here, we report an electrophysiological investigation of intracellular solute-binding to the human serotonin transporter (SERT) expressed in HEK-293 cells. We measured currents induced by rapid application of serotonin employing varying intracellular (co-)substrate concentrations and interpreted the data using kinetic modeling. Our measurements revealed that the induction of the substrate-exchange mode depends on both voltage and intracellular Na + concentrations because intracellular Na + release occurs before serotonin release and is highly electrogenic. This voltage dependence was blunted by electrogenic binding of intracellular K + and, notably, also H + In addition, our data suggest that Cl - is bound to SERT during the entire catalytic cycle. Our experiments, therefore, document an essential role of electrogenic binding of K + or of H + to the inward-facing conformation of SERT in (i) cancelling out the electrogenic nature of intracellular Na + release and (ii) in selecting the forward-transport over the substrate-exchange mode. Finally, the kinetics of intracellular Na + release and K + (or H + ) binding result in a voltage-independent rate-limiting step where SERT may return to the outward-facing state in a KCl- or HCl-bound form. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology.

PubMed

Tian, Zhiqiang; Yu, Qin; Xie, Yunchang; Li, Fengqian; Lu, Yi; Dong, Xiaochun; Zhao, Weili; Qi, Jianping; Wu, Wei

2016-08-01

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles. NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references. NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation. Controlled release of integral NLCs is achieved by the osmotic pump strategy.

Development of gastro intestinal sustained release tablet formulation containing acryl-EZE and pH-dependent swelling HPMC K 15 M.

PubMed

Lamoudi, Lynda; Chaumeil, Jean Claude; Daoud, Kamel

2012-05-01

The aim of this study was to evaluate physical properties and release from matrix tablets containing different ratios of HPMC 15 M and Acryl-EZE. A further aim is to assess their suitability for pH dependent controlled release. Matrix tablets containing HPMC 15 M and Acryl-EZE were manufactured using a fluidized bed. The release from this matrix using Sodium Diclofenac (SD) as model drug is studied in two dissolution media (0.1 N HCl or pH = 6.8 phosphate buffer solution); the release rate, mechanism, and pH dependence were characterized by fitting four kinetic models and by using a similarity factor analysis. The obtained results revealed that the presence of Acryl-EZE in the matrix tablets is effective in protecting the dosage forms from release in acid environments such as gastric fluid. In pH = 6.8 phosphate buffer, the drug release rate and mechanism of release from all matrices is mainly controlled by HPMC 15 M. The model of Korsmeyer-Peppas was found to fit experimental dissolution results.

Kinetics and Antioxidant Capacity of Proanthocyanidins Encapsulated in Zein Electrospun Fibers by Cyclic Voltammetry.

PubMed

Wang, Hualin; Hao, Lilan; Niu, Baicheng; Jiang, Suwei; Cheng, Junfeng; Jiang, Shaotong

2016-04-20

The proanthocyanidins encapsulated in zein (zein-PA) fibers was via electrospinning technique. The kinetics and antioxidant capacity of PA from zein fibers was investigated by cyclic voltammetry. Circular dichroism was used to investigate the secondary structure change of zein and its influence on the shape of fibers. The addition of PA caused a significant increase in viscosity and made fibers wider. These hydrogen bonds between zein and PA molecules would favor the α-helix change and decrease the β-folds of zein in electrospinning solutions, leading to a round-shaped tendency of fibers and enhancing the thermal properties slightly. Zein-PA fibers showed high encapsulation efficiency close to 100%, and the encapsulated PA retained its antioxidant capacity in fibers. Zein-PA fibers showed a good controlled release toward PA, and the predominant release of PA from fibers was Fickian diffusion, which could be well described by first-order model and Hixson-Crowell model.

Pectin gel vehicles for controlled fragrance delivery.

PubMed

Liu, LinShu; Chen, Guoying; Fishman, Marshall L; Hicks, Kevin B

2005-01-01

Using citronellal as a model compound, pectin gels formulations were evaluated for the controlled fragrance release by kinetic and static methods. The pectins with higher degrees of esterification induced a stronger molecular association with the nonpolar fragrance. This resulted in a prolonged duration of fragrance release and the limitation of fragrance adsorption to the receptor skin layers. The increase in pectin concentrations suppressed the fragrance release by a diffusion mechanism. Blocking the carboxyl groups of pectin with calcium ions reduces the hydrophilicity of pectin and provides physical barriers for citronellal diffusion. The pectin/calcium microparticles are promising materials for controlled fragrance release.

In vitro and in vivo evaluation of novel ciprofloxacin-releasing silicone hydrogel contact lenses.

PubMed

Hui, Alex; Willcox, Mark; Jones, Lyndon

2014-07-15

The purpose of this study was to evaluate ciprofloxacin-releasing silicone hydrogel contact lens materials in vitro and in vivo for the treatment of microbial keratitis. Model silicone hydrogel contact lens materials were manufactured using a molecular imprinting technique to modify ciprofloxacin release kinetics. Various contact lens properties, including light transmission and surface wettability, were determined, and the in vitro ciprofloxacin release kinetics elucidated using fluorescence spectrophotometry. The materials then were evaluated for their ability to inhibit Pseudomonas aeruginosa growth in vitro and in an in vivo rabbit model of microbial keratitis. Synthesized lenses had similar material properties to commercial contact lens materials. There was a decrease in light transmission in the shorter wavelengths due to incorporation of the antibiotic, but over 80% light transmission between 400 and 700 nm. Modified materials released for more than 8 hours, significantly longer than unmodified controls (P < 0.05). In vivo, there was no statistically significant difference between the number of colony-forming units (CFU) recovered from corneas treated with eye drops and those treated with one of two modified contact lenses (P > 0.05), which is significantly less than corneas treated with unmodified control lenses or those that received no treatment at all (P < 0.05). These novel contact lenses designed for the extended release of ciprofloxacin may be beneficial to supplement or augment future treatments of sight-threatening microbial keratitis. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Optimization of primaquine diphosphate tablet formulation for controlled drug release using the mixture experimental design.

PubMed

Duque, Marcelo Dutra; Kreidel, Rogério Nepomuceno; Taqueda, Maria Elena Santos; Baby, André Rolim; Kaneko, Telma Mary; Velasco, Maria Valéria Robles; Consiglieri, Vladi Olga

2013-01-01

A tablet formulation based on hydrophilic matrix with a controlled drug release was developed, and the effect of polymer concentrations on the release of primaquine diphosphate was evaluated. To achieve this purpose, a 20-run, four-factor with multiple constraints on the proportions of the components was employed to obtain tablet compositions. Drug release was determined by an in vitro dissolution study in phosphate buffer solution at pH 6.8. The polynomial fitted functions described the behavior of the mixture on simplex coordinate systems to study the effects of each factor (polymer) on tablet characteristics. Based on the response surface methodology, a tablet composition was optimized with the purpose of obtaining a primaquine diphosphate release closer to a zero order kinetic. This formulation released 85.22% of the drug for 8 h and its kinetic was studied regarding to Korsmeyer-Peppas model, (Adj-R(2) = 0.99295) which has confirmed that both diffusion and erosion were related to the mechanism of the drug release. The data from the optimized formulation were very close to the predictions from statistical analysis, demonstrating that mixture experimental design could be used to optimize primaquine diphosphate dissolution from hidroxypropylmethyl cellulose and polyethylene glycol matrix tablets.

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.

Bioreactor validation and biocompatibility of Ag/poly(N-vinyl-2-pyrrolidone) hydrogel nanocomposites.

PubMed

Jovanović, Zeljka; Radosavljević, Aleksandra; Kačarević-Popović, Zorica; Stojkovska, Jasmina; Perić-Grujić, Aleksandra; Ristić, Mirjana; Matić, Ivana Z; Juranić, Zorica D; Obradovic, Bojana; Mišković-Stanković, Vesna

2013-05-01

Silver/poly(N-vinyl-2-pyrrolidone) (Ag/PVP) nanocomposites containing Ag nanoparticles at different concentrations were synthesized using γ-irradiation. Cytotoxicity of the obtained nanocomposites was determined by MTT assay in monolayer cultures of normal human immunocompetent peripheral blood mononuclear cells (PBMC) that were either non-stimulated or stimulated to proliferate by mitogen phytohemagglutinin (PHA), as well as in human cervix adenocarcinoma cell (HeLa) cultures. Silver release kinetics and mechanical properties of nanocomposites were investigated under bioreactor conditions in the simulated body fluid (SBF) at 37°C. The release of silver was monitored under static conditions, and in two types of bioreactors: perfusion bioreactors and a bioreactor with dynamic compression coupled with SBF perfusion simulating in vivo conditions in articular cartilage. Ag/PVP nanocomposites exhibited slight cytotoxic effects against PBMC at the estimated concentration of 0.4 μmol dm(-3), with negligible variations observed amongst different cell cultures investigated. Studies of the silver release kinetics indicated internal diffusion as the rate limiting step, determined by statistically comparable results obtained at all investigated conditions. However, silver release rate was slightly higher in the bioreactor with dynamic compression coupled with SBF perfusion as compared to the other two systems indicating the influence of dynamic compression. Modelling of silver release kinetics revealed potentials for optimization of Ag/PVP nanocomposites for particular applications as wound dressings or soft tissue implants. Copyright © 2013 Elsevier B.V. All rights reserved.

Natural gum-type biopolymers as potential modified nonpolar drug release systems.

PubMed

Salamanca, Constain H; Yarce, Cristhian J; Moreno, Roger A; Prieto, Vanessa; Recalde, Juanita

2018-06-01

In this work, the relationship between surface properties and drug release mechanism from binary composition tablets formed by quetiapine fumarate and biopolymer materials was studied. The biopolymers correspond to xanthan and tragacanth gums, which are projected as modified drug release systems. The surface studies were carried out by the sessile drop method, while the surface free energy (SFE) was determinate through Young-Dupree and OWRK semi-empirical models. On the other hand, the drug release studies were performed by in vitro dissolution tests, where the data were analyzed through kinetic models of zero order, first order, Higuchi, and Korsmeyer-Peppas. The results showed that depending on the type and the proportion of biopolymer, surface properties, and the drug release processes are significantly affected, wherein tragacanth gum present a usual erosion mechanism, while xanthan gum describes a swelling mechanism that controls the release of the drug. Copyright © 2018 Elsevier Ltd. All rights reserved.

Indistinguishability and identifiability of kinetic models for the MurC reaction in peptidoglycan biosynthesis.

PubMed

Hattersley, J G; Pérez-Velázquez, J; Chappell, M J; Bearup, D; Roper, D; Dowson, C; Bugg, T; Evans, N D

2011-11-01

An important question in Systems Biology is the design of experiments that enable discrimination between two (or more) competing chemical pathway models or biological mechanisms. In this paper analysis is performed between two different models describing the kinetic mechanism of a three-substrate three-product reaction, namely the MurC reaction in the cytoplasmic phase of peptidoglycan biosynthesis. One model involves ordered substrate binding and ordered release of the three products; the competing model also assumes ordered substrate binding, but with fast release of the three products. The two versions are shown to be distinguishable; however, if standard quasi-steady-state assumptions are made distinguishability cannot be determined. Once model structure uniqueness is ensured the experimenter must determine if it is possible to successfully recover rate constant values given the experiment observations, a process known as structural identifiability. Structural identifiability analysis is carried out for both models to determine which of the unknown reaction parameters can be determined uniquely, or otherwise, from the ideal system outputs. This structural analysis forms an integrated step towards the modelling of the full pathway of the cytoplasmic phase of peptidoglycan biosynthesis. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Effects of pore CaCO3 form agencies on dissolution mechanisms of amoxicillin drugs encapsulated in hydrogels full-IPN chitosan N-vinyl caprolactam

NASA Astrophysics Data System (ADS)

Budianto, Emil; Fauzia, Maghfira

2018-04-01

The administration of amoxicillin trihydrate in Helicobacter pylori infection is not effective enough because the conventional preparations used have a short retention time in the stomach. To overcome this problem, amoxicillin trihydrate was encapsulated into the floating drug delivery matrix-matrix. In this study, the full-ipn acetaldehyde crosslinked hydrogel (N-vinyl caprolactam) was synthesized with a 10% CaCO3 pore forming agent and then encapsulated on amoxicillin trihydrate and studied the mechanism of drug dissolution with its kinetic kinetics approach. The K-PNVCL Hydrogel produces optimal properties which are then loaded with amoxicillin trihydrate in situ and post loading. In this research, we have got the percentage of swelling, floating time, the efficiency of in situ and post loading 873%; 3.15 minutes; 99.8% and 99.4%. The dissolution test was performed on amoxicillin trihydrate which had been encapsulated K-PNVCL hydrogel in vitro at pH 1.2 resulting in 94.5% for in situ loading and 98.5% for post loading. Results of the kinetics of drug release for post loading and in situ loading methods tend to follow the Higuchi model kinetics. The drug release mechanism occurs by Fickian diffusion. Proof of drug release mechanism from K-PNVCL hydrogel matrix is further done by Scanning Electron Microscope (SEM) instrument.

A combined spectroscopic and plasma chemical kinetic analysis of ionospheric samarium releases

NASA Astrophysics Data System (ADS)

Holmes, Jeffrey M.; Dressler, Rainer A.; Pedersen, Todd R.; Caton, Ronald G.; Miller, Daniel

2017-05-01

Two rocket-borne releases of samarium vapor in the upper atmosphere occurred in May 2013, as part of the Metal Oxide Space Clouds experiment. The releases were characterized by a combination of optical and RF diagnostic instruments located at the Roi-Namur launch site and surrounding islands and atolls. The evolution of the optical spectrum of the solar-illuminated cloud was recorded with a spectrograph covering a 400-800 nm spectral range. The spectra exhibit two distinct spectral regions centered at 496 and 636 nm within which the relative intensities change insignificantly. The ratio between the integrated intensities within these regions, however, changes with time, suggesting that they are associated with different species. With the help of an equilibrium plasma spectral model we attribute the region centered at 496 nm to neutral samarium atoms (Sm I radiance) and features peaking at 649 nm to a molecular species. No evidence for structure due to Sm+ (Sm II) is identified. The persistence of the Sm I radiance suggests a high dissociative recombination rate for the chemi-ionization product, SmO+. A one-dimensional plasma chemical kinetic model of the evolution of the density ratio NSmO/NSm(t) demonstrates that the molecular feature peaking at 649 nm can be attributed to SmO radiance. SmO+ radiance is not identified. By adjusting the Sm vapor mass of the chemical kinetic model input to match the evolution of the total electron density determined by ionosonde data, we conclude that less than 5% of the payload samarium was vaporized.

Active chlorine and nitric oxide formation from chemical rocket plume afterburning

NASA Astrophysics Data System (ADS)

Leone, D. M.; Turns, S. R.

Chlorine and oxides of nitrogen (NO(x)) released into the atmosphere contribute to acid rain (ground level or low-altitude sources) and ozone depletion from the stratosphere (high-altitude sources). Rocket engines have the potential for forming or activating these pollutants in the rocket plume. For instance, H2/O2 rockets can produce thermal NO(x) in their plumes. Emphasis, in the past, has been placed on determining the impact of chlorine release on the stratosphere. To date, very little, if any, information is available to understand what contribution NO(x) emissions from ground-based engine testing and actual rocket launches have on the atmosphere. The goal of this work is to estimate the afterburning emissions from chemical rocket plumes and determine their local stratospheric impact. Our study focuses on the space shuttle rocket motors, which include both the solid rocket boosters (SRB's) and the liquid propellant main engines (SSME's). Rocket plume afterburning is modeled employing a one-dimensional model incorporating two chemical kinetic systems: chemical and thermal equilibria with overlayed nitric oxide chemical kinetics (semi equilibrium) and full finite-rate chemical kinetics. Additionally, the local atmospheric impact immediately following a launch is modeled as the emissions diffuse and chemically react in the stratosphere.

Active chlorine and nitric oxide formation from chemical rocket plume afterburning

NASA Technical Reports Server (NTRS)

Leone, D. M.; Turns, S. R.

1994-01-01

Chlorine and oxides of nitrogen (NO(x)) released into the atmosphere contribute to acid rain (ground level or low-altitude sources) and ozone depletion from the stratosphere (high-altitude sources). Rocket engines have the potential for forming or activating these pollutants in the rocket plume. For instance, H2/O2 rockets can produce thermal NO(x) in their plumes. Emphasis, in the past, has been placed on determining the impact of chlorine release on the stratosphere. To date, very little, if any, information is available to understand what contribution NO(x) emissions from ground-based engine testing and actual rocket launches have on the atmosphere. The goal of this work is to estimate the afterburning emissions from chemical rocket plumes and determine their local stratospheric impact. Our study focuses on the space shuttle rocket motors, which include both the solid rocket boosters (SRB's) and the liquid propellant main engines (SSME's). Rocket plume afterburning is modeled employing a one-dimensional model incorporating two chemical kinetic systems: chemical and thermal equilibria with overlayed nitric oxide chemical kinetics (semi equilibrium) and full finite-rate chemical kinetics. Additionally, the local atmospheric impact immediately following a launch is modeled as the emissions diffuse and chemically react in the stratosphere.

Influence of Organic Matter - Mineral Interfacial Reactions on Metal(loid) Speciation and Bioaccessibility

NASA Astrophysics Data System (ADS)

Chorover, J.; Kong, S.; Root, R. A.; Thomas, A.

2015-12-01

Bioaccessibility of contaminant metals in geomedia is often measured on the basis of kinetic release to solution during in vitro reaction with biofluid simulants. We postulate that development of a predictive-mechanistic understanding of bioaccessibility requires knowledge of metal(loid) molecular speciation upon sample introduction, as well as its change over the course of the in vitro reaction. Our results - including data from batch, column, mesocosm and field studies pertaining to arsenic, lead, and zinc contaminated materials - indicate the strong influence of organic matter and associated biological activity on metal(loid) speciation in mine tailings and related model systems. Furthermore, presence/absence of organic matter during bioassays affects the kinetics of metal(loid) release into biofluid simulants through multiple mechanisms.

Self-assembly of model graft copolymers of agarose and weak polyelectrolyte-based amphiphilic diblock copolymers: controlled drug release and degradation.

PubMed

Muppalla, Ravikumar; Jewrajka, Suresh K; Prasad, Kamalesh

2013-06-01

Polysaccharide-based copolymers are promising biomaterials due to their biocompatibility and biodegradability. For potential biomedical applications the copolymer as a whole and all the degraded species must be biocompatible and easily removable from the system. In this regards, new model pH-responsive seaweed agarose (Agr) grafted with weak polyelectrolyte-based well-defined amphiphilic block copolymers ca. poly[(methyl methacrylate)-b-(2-dimethylamino)ethyl methacrylate)] (PMMA-b-PDMA) were designed and synthesized to study the self-assembly, degradation, and in vitro hydrophobic/hydrophilic drug release behavior. The graft copolymer solutions display extremely low critical micelle concentration (CMC) and form pH responsive stable micelles. The degradation study of the graft copolymer reveals that the entire degraded components are well soluble/dispersible in water due to formation of mixed micelles. The micelles are also strongly adsorbed on the mica surface owing to electrostatic interaction. One application of the graft copolymer micelles is that it can entrap both hydrophilic and poorly water soluble hydrophobic drugs effectively and exhibit slow release kinetics. The release kinetics of both the hydrophilic and poorly water soluble hydrophobic drugs change with pH as well as with the composition of the graft copolymer. Copyright © 2012 Wiley Periodicals, Inc.

PLGA-Mesoporous Silicon Microspheres for the in Vivo Controlled Temporospatial Delivery of Proteins.

PubMed

Minardi, Silvia; Pandolfi, Laura; Taraballi, Francesca; De Rosa, Enrica; Yazdi, Iman K; Liu, Xeuwu; Ferrari, Mauro; Tasciotti, Ennio

2015-08-05

In regenerative medicine, the temporospatially controlled delivery of growth factors (GFs) is crucial to trigger the desired healing mechanisms in the target tissues. The uncontrolled release of GFs has been demonstrated to cause severe side effects in the surrounding tissues. The aim of this study was to optimize a translational approach for the fine temporal and spatial control over the release of proteins, in vivo. Hence, we proposed a newly developed multiscale composite microsphere based on a core consisting of the nanostructured silicon multistage vector (MSV) and a poly(dl-lactide-co-glycolide) acid (PLGA) outer shell. Both of the two components of the resulting composite microspheres (PLGA-MSV) can be independently tailored to achieve multiple release kinetics contributing to the control of the release profile of a reporter protein in vitro. The influence of MSV shape (hemispherical or discoidal) and size (1, 3, or 7 μm) on PLGA-MSV's morphology and size distribution was investigated. Second, the copolymer ratio of the PLGA used to fabricate the outer shell of PLGA-MSV was varied. The composites were fully characterized by optical microscopy, scanning electron microscopy, ζ potential, Fourier transform infrared spectroscopy, and thermogravimetric analysis-differential scanning calorimetry, and their release kinetics over 30 days. PLGA-MSV's biocompatibility was assessed in vitro with J774 macrophages. Finally, the formulation of PLGA-MSV was selected, which concurrently provided the most consistent microsphere size and allowed for a zero-order release kinetic. The selected PLGA-MSVs were injected in a subcutaneous model in mice, and the in vivo release of the reporter protein was followed over 2 weeks by intravital microscopy, to assess if the zero-order release was preserved. PLGA-MSV was able to retain the payload over 2 weeks, avoiding the initial burst release typical of most drug delivery systems. Finally, histological evaluation assessed the biocompatibility of the platform in vivo.

Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

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

Manzano, J. Sebastian; Singappuli-Arachchige, Dilini; Parikh, Bosky L.

Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticlesmore » (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. Here, the results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.« less

Fine-tuning the release of molecular guests from mesoporous silicas by controlling the orientation and mobility of surface phenyl substituents

DOE PAGES

Manzano, J. Sebastian; Singappuli-Arachchige, Dilini; Parikh, Bosky L.; ...

2017-12-05

Phenyl-functionalized mesoporous silica materials were used to explore the effect of non-covalent interactions on the release of Ibuprofen into simulated body fluid. Variations in orientation and conformational mobility of the surface phenyl groups were introduced by selecting different structural precursors: a rigid upright orientation was obtained using phenyl groups directly bound to surface Si atoms (Ph-MSN), mobile groups were produced by using ethylene linkers to connect phenyl groups to the surface (PhEt-MSN), and groups co-planar to the surface were obtained by synthesizing a phenylene-bridged periodic mesoporous organosilica (Ph-PMO). The Ibuprofen release profiles from these materials and non-functionalized mesoporous silica nanoparticlesmore » (MSN) were analyzed using an adsorption-diffusion model. The model provided kinetic and thermodynamic parameters that evidenced fundamental differences in drug-surface interactions between the materials. All phenyl-bearing materials show lower Ibuprofen initial release rates than bare MSN. The conformationally locked Ph-MSN and Ph-PMO have stronger interactions with the drug (negative ΔG of adsorption) than the flexible PhEt-MSN and bare MSN (positive ΔG of adsorption). These differences in strength of adsorption are consistent with differences between interaction geometries obtained from DFT calculations. B3LYP-D3-optimized models show that π-π interactions contribute more to drug adsorption than H-bonding with silanol groups. Here, the results suggest that the type and geometry of interactions control the kinetics and extent of drug release, and should therefore serve as a guide to design new drug delivery systems with precise release behaviors customized to any desired target.« less

Mechanistic Kinetic Modeling of Thiol-Michael Addition Photopolymerizations via Photocaged "Superbase" Generators: An Analytical Approach.

PubMed

Claudino, Mauro; Zhang, Xinpeng; Alim, Marvin D; Podgórski, Maciej; Bowman, Christopher N

2016-11-08

A kinetic mechanism and the accompanying mathematical framework are presented for base-mediated thiol-Michael photopolymerization kinetics involving a photobase generator. Here, model kinetic predictions demonstrate excellent agreement with a representative experimental system composed of 2-(2-nitrophenyl)propyloxycarbonyl-1,1,3,3-tetramethylguanidine (NPPOC-TMG) as a photobase generator that is used to initiate thiol-vinyl sulfone Michael addition reactions and polymerizations. Modeling equations derived from a basic mechanistic scheme indicate overall polymerization rates that follow a pseudo-first-order kinetic process in the base and coreactant concentrations, controlled by the ratio of the propagation to chain-transfer kinetic parameters ( k p / k CT ) which is dictated by the rate-limiting step and controls the time necessary to reach gelation. Gelation occurs earlier as the k p / k CT ratio reaches a critical value, wherefrom gel times become nearly independent of k p / k CT . The theoretical approach allowed determining the effect of induction time on the reaction kinetics due to initial acid-base neutralization for the photogenerated base caused by the presence of protic contaminants. Such inhibition kinetics may be challenging for reaction systems that require high curing rates but are relevant for chemical systems that need to remain kinetically dormant until activated although at the ultimate cost of lower polymerization rates. The pure step-growth character of this living polymerization and the exhibited kinetics provide unique potential for extended dark-cure reactions and uniform material properties. The general kinetic model is applicable to photobase initiators where photolysis follows a unimolecular cleavage process releasing a strong base catalyst without cogeneration of intermediate radical species.

Self-assembling N-(9-Fluorenylmethoxycarbonyl)-l-Phenylalanine hydrogel as novel drug carrier.

PubMed

Snigdha, Kirti; Singh, Brijesh K; Mehta, Abijeet Singh; Tewari, R P; Dutta, P K

2016-12-01

Supramolecular hydrogel as a novel drug carrier was prepared from N-(9-Fluorenylmethoxycarbonyl) (Fmoc) modified l-phenylalanine. Its different properties like stability at different pH, temperature and rheology were evaluated in reference to salicylic acid (SA) as a model drug, entrapped in the supramolecular hydrogel network. The release behaviour of SA drug in supramolecular hydrogel was investigated by UV-vis spectroscopy. The influence of hydrogelator, pH values of the accepting media, temperature and concentration of SA drug on the release behaviour was investigated under static conditions. The results indicated that the release rate of SA in the supramolecular hydrogels was slightly retarded with an increase of the hydrogelator concentration. Also, the release rates of SA increased with an increase of temperature and its concentration. Furthermore, the release behaviour of SA was found to be different at various pH values in buffers. The study of the release kinetics indicated that the release behaviour of SA from the carrier was in accord with the Peppas model and the diffusion controlled mechanism involved in the Fickian model. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

Comminution of solids caused by kinetic energy of high shear strain rate, with implications for impact, shock, and shale fracturing

PubMed Central

Bažant, Zdeněk P.; Caner, Ferhun C.

2013-01-01

Although there exists a vast literature on the dynamic comminution or fragmentation of rocks, concrete, metals, and ceramics, none of the known models suffices for macroscopic dynamic finite element analysis. This paper outlines the basic idea of the macroscopic model. Unlike static fracture, in which the driving force is the release of strain energy, here the essential idea is that the driving force of comminution under high-rate compression is the release of the local kinetic energy of shear strain rate. The density of this energy at strain rates >1,000/s is found to exceed the maximum possible strain energy density by orders of magnitude, making the strain energy irrelevant. It is shown that particle size is proportional to the −2/3 power of the shear strain rate and the 2/3 power of the interface fracture energy or interface shear stress, and that the comminution process is macroscopically equivalent to an apparent shear viscosity that is proportional (at constant interface stress) to the −1/3 power of this rate. A dimensionless indicator of the comminution intensity is formulated. The theory was inspired by noting that the local kinetic energy of shear strain rate plays a role analogous to the local kinetic energy of eddies in turbulent flow. PMID:24218624

In vitro-in vivo evaluation of in situ gelling and thermosensitive ketoprofen liquid suppositories.

PubMed

Ozgüney, Işık; Kardhiqi, Anita; Yıldız, Gülbeyaz; Ertan, Gökhan

2014-12-01

The main objective of this study was to investigate the release and pharmacokinetic profiles of ketoprofen (KP) from developed thermosensitive and mucoadhesive liquid suppositories. Thermosensitive liquid suppositories were prepared using KP, poloxamer 407 (P 407), poloxamer 188 (P 188) and various amounts of different mucoadhesive polymers. In vitro release studies was monitored by the USP XXVI paddle method. The results thus obtained were evaluated kinetically and mechanism of release was analyzed. Identification of poloxamer gel localization in vivo was conducted using white male rabbits by adding 1 % methylene blue. For in vivo studies, twenty-four white male rabbits were randomly divided into three groups. The rabbits in each group were administered with liquid suppository F1 [P407/P188/KP (4/20/2.5 %)], F5 [P407/P188/KP/C (4/20/2.5/0.8 %)] or conventional suppository (F-C) into the rectum. The plasma concentration of KP was analyzed by high performance liquid chromatography (HPLC). C max, AUC, MRT and T max were evaluated. The release of KP was variously affected by the mucoadhesive polymers. In vitro release studies showed that Carbopol 934 P(C) has significant effect on release rate among the mucoadhesive polymers. When the formulations were evaluated kinetically, different kinetic models were obtained. Formulation F6 [P407/P188/KP/C (4/20/2.5/1.6 %)] which contains the highest C concentration and very high viscosity, shows a significantly better fit with Higuchi kinetic model. n value of this formulation was also found approximately 0.5. n exponent results of the other formulations showed that KP might be released from the suppositories by non-Fickian diffusion. Identification of poloxamer gel localization in vivo showed that the suppositories remain in the rectum without leakage after administration. With regard to the results of in vivo studies, the AUC6→14 values of KP in liquid suppository containing C are significantly higher than those in liquid suppository without C. MRT0→24 and MRT0→∞ values of liquid suppository containing C are significantly higher than those in liquid suppository without C and conventional suppository. Conventional suppository and liquid suppository without C significantly gave faster time to reach the maximum plasma concentrations of KP. With regard to the in vitro and in vivo experiments, liquid suppository formulation F5 might be a promising formulation for the development of an effective rectal dosage form.

Naproxen conjugated mPEG-PCL micelles for dual triggered drug delivery.

PubMed

Karami, Zahra; Sadighian, Somayeh; Rostamizadeh, Kobra; Parsa, Maliheh; Rezaee, Saeed

2016-04-01

A conjugate of the NSAIDs drug, naproxen, with diblock methoxy poly(ethylene glycol)-poly(ε-caprolactone) (mPEG-PCL) copolymer was synthesized by the reaction of copolymer with naproxen in the presence of dicyclohexylcarbodiimide and dimethylaminopyridine. The naproxen conjugated copolymers were characterized with different techniques including (1)HNMR, FTIR, and DSC. The naproxen conjugated mPEG-PCL copolymers were self-assembled into micelles in aqueous solution. The TEM analysis revealed that the micelles had the average size of about 80 nm. The release behavior of conjugated copolymer was investigated in two different media with the pH values of 7.4 and 5.2. In vitro release study showed that the drug release rate was dependant on pH as it was higher at lower pH compared to neutral pH. Another feature of the conjugated micelles was a more sustained release profile compared to the conjugated copolymer. The kinetic of the drug release from naproxen conjugated micelles under different values of pH was also investigated by different kinetic models such as first-order, Makoid-Banakar, Weibull, Logistic, and Gompertz. Copyright © 2015 Elsevier B.V. All rights reserved.

Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury

PubMed Central

Kuster, Diederik W. D.; Cardenas-Ospina, Adriana; Miller, Lawson; Liebetrau, Christoph; Troidl, Christian; Nef, Holger M.; Möllmann, Helge; Hamm, Christian W.; Pieper, Karen S.; Mahaffey, Kenneth W.; Kleiman, Neal S.; Stuyvers, Bruno D.; Marian, Ali J.

2013-01-01

Diagnosis of myocardial infarction (MI) is based on ST-segment elevation on electrocardiographic evaluation and/or elevated plasma cardiac troponin (cTn) levels. However, troponins lack the sensitivity required to detect the onset of MI at its earliest stages. Therefore, to confirm its viability as an ultra-early biomarker of MI, this study investigates the release kinetics of cardiac myosin binding protein-C (cMyBP-C) in a porcine model of MI and in two human cohorts. Release kinetics of cMyBP-C were determined in a porcine model of MI (n = 6, pigs, either sex) by measuring plasma cMyBP-C level serially from 30 min to 14 days after coronary occlusion, with use of a custom-made immunoassay. cMyBP-C plasma levels were increased from baseline (76 ± 68 ng/l) at 3 h (767 ± 211 ng/l) and peaked at 6 h (2,418 ± 780 ng/l) after coronary ligation. Plasma cTnI, cTnT, and myosin light chain-3 levels were all increased 6 h after ligation. In a cohort of patients (n = 12) with hypertrophic obstructive cardiomyopathy undergoing transcoronary ablation of septal hypertrophy, cMyBP-C was significantly increased from baseline (49 ± 23 ng/l) in a time-dependent manner, peaking at 4 h (560 ± 273 ng/l). In a cohort of patients with non-ST segment elevation MI (n = 176) from the SYNERGY trial, cMyBP-C serum levels were significantly higher (7,615 ± 4,514 ng/l) than those in a control cohort (416 ± 104 ng/l; n = 153). cMyBP-C is released in the blood rapidly after cardiac damage and therefore has the potential to positively mark the onset of MI. PMID:24337456

A review of mathematical modeling and simulation of controlled-release fertilizers.

PubMed

Irfan, Sayed Ameenuddin; Razali, Radzuan; KuShaari, KuZilati; Mansor, Nurlidia; Azeem, Babar; Ford Versypt, Ashlee N

2018-02-10

Nutrients released into soils from uncoated fertilizer granules are lost continuously due to volatilization, leaching, denitrification, and surface run-off. These issues have caused economic loss due to low nutrient absorption efficiency and environmental pollution due to hazardous emissions and water eutrophication. Controlled-release fertilizers (CRFs) can change the release kinetics of the fertilizer nutrients through an abatement strategy to offset these issues by providing the fertilizer content in synchrony with the metabolic needs of the plants. Parametric analysis of release characteristics of CRFs is of paramount importance for the design and development of new CRFs. However, the experimental approaches are not only time consuming, but they are also cumbersome and expensive. Scientists have introduced mathematical modeling techniques to predict the release of nutrients from the CRFs to elucidate fundamental understanding of the dynamics of the release processes and to design new CRFs in a shorter time and with relatively lower cost. This paper reviews and critically analyzes the latest developments in the mathematical modeling and simulation techniques that have been reported for the characteristics and mechanisms of nutrient release from CRFs. The scope of this review includes the modeling and simulations techniques used for coated, controlled-release fertilizers. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of unique release kinetics of serotonin from guinea-pig and human enterochromaffin cells

PubMed Central

Raghupathi, Ravinarayan; Duffield, Michael D; Zelkas, Leah; Meedeniya, Adrian; Brookes, Simon J H; Sia, Tiong Cheng; Wattchow, David A; Spencer, Nick J; Keating, Damien J

2013-01-01

The major source of serotonin (5-HT) in the body is the enterochromaffin (EC) cells lining the intestinal mucosa of the gastrointestinal tract. Despite the fact that EC cells synthesise ∼95% of total body 5-HT, and that this 5-HT has important paracrine and endocrine roles, no studies have investigated the mechanisms of 5-HT release from single primary EC cells. We have developed a rapid primary culture of guinea-pig and human EC cells, allowing analysis of single EC cell function using electrophysiology, electrochemistry, Ca2+ imaging, immunocytochemistry and 3D modelling. Ca2+ enters EC cells upon stimulation and triggers quantal 5-HT release via L-type Ca2+ channels. Real time amperometric techniques reveal that EC cells release 5-HT at rest and this release increases upon stimulation. Surprisingly for an endocrine cell storing 5-HT in large dense core vesicles (LDCVs), EC cells release 70 times less 5-HT per fusion event than catecholamine released from similarly sized LDCVs in endocrine chromaffin cells, and the vesicle release kinetics instead resembles that observed in mammalian synapses. Furthermore, we measured EC cell density along the gastrointestinal tract to create three-dimensional (3D) simulations of 5-HT diffusion using the minimal number of variables required to understand the physiological relevance of single cell 5-HT release in the whole-tissue milieu. These models indicate that local 5-HT levels are likely to be maintained around the activation threshold for mucosal 5-HT receptors and that this is dependent upon stimulation and location within the gastrointestinal tract. This is the first study demonstrating single cell 5-HT release in primary EC cells. The mode of 5-HT release may represent a unique mode of exocytosis amongst endocrine cells and is functionally relevant to gastrointestinal sensory and motor function. PMID:24099799

Role of Metal Electronegativity in the Dehydrogenation Thermodynamics and Kinetics of Composite Metal Borohydride-LiNH2 Hydrogen Storage Materials.

PubMed

Bai, Ying; Pei, Ziwei; Wu, Feng; Wu, Chuan

2018-03-21

The composites of M(BH 4 ) n -LiNH 2 (1/2 n molar ratio, n = 1 or 2, M = Ca, Mg, Li) were synthesized by liquid ball milling. Samples were characterized by X-ray diffraction, thermogravimetry-differential thermal analysis-mass spectroscopy (TG-DTA-MS), and kinetic models (Achar differential/Coats-Redfern integral method). The higher-electronegativity metal M in M(BH 4 ) n -4LiNH 2 (M = Ca, Mg) samples not only enables [BH 4 ] - group to release easily, so as to facilitate the interaction of [BH 4 ] - and [NH 2 ] - groups, but also restrains the NH 3 release and slightly decreases the onset dehydrogenation temperature concluded by TG-MS. Moreover, in stage 1 (200-350 °C), the kinetics performances of M(BH 4 ) n -4LiNH 2 (M = Ca, Mg) samples are distinctly improved, that is, the activation energies of them are reduced by ca. 30% compared to those of sample LiBH 4 -2LiNH 2 . The outstanding contribution of the replacement of M(BH 4 ) n with high-electronegativity metal ion is to both improve the kinetics performance by changing the kinetics mechanism and decrease the temperature range of the initial dehydrogenation region.

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.

C. botulinum inactivation kinetics implemented in a computational model of a high-pressure sterilization process.

PubMed

Juliano, Pablo; Knoerzer, Kai; Fryer, Peter J; Versteeg, Cornelis

2009-01-01

High-pressure, high-temperature (HPHT) processing is effective for microbial spore inactivation using mild preheating, followed by rapid volumetric compression heating and cooling on pressure release, enabling much shorter processing times than conventional thermal processing for many food products. A computational thermal fluid dynamic (CTFD) model has been developed to model all processing steps, including the vertical pressure vessel, an internal polymeric carrier, and food packages in an axis-symmetric geometry. Heat transfer and fluid dynamic equations were coupled to four selected kinetic models for the inactivation of C. botulinum; the traditional first-order kinetic model, the Weibull model, an nth-order model, and a combined discrete log-linear nth-order model. The models were solved to compare the resulting microbial inactivation distributions. The initial temperature of the system was set to 90 degrees C and pressure was selected at 600 MPa, holding for 220 s, with a target temperature of 121 degrees C. A representation of the extent of microbial inactivation throughout all processing steps was obtained for each microbial model. Comparison of the models showed that the conventional thermal processing kinetics (not accounting for pressure) required shorter holding times to achieve a 12D reduction of C. botulinum spores than the other models. The temperature distribution inside the vessel resulted in a more uniform inactivation distribution when using a Weibull or an nth-order kinetics model than when using log-linear kinetics. The CTFD platform could illustrate the inactivation extent and uniformity provided by the microbial models. The platform is expected to be useful to evaluate models fitted into new C. botulinum inactivation data at varying conditions of pressure and temperature, as an aid for regulatory filing of the technology as well as in process and equipment design.

[Preparation and in vitro release characteristics of vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles].

PubMed

Tan, Rong; Liu, Ying; Feng, Nianping; Zhao, Jihui

2011-06-01

To prepare vincristine sulphate loaded poly (butylcyanoacrylate) nanoparticles (VCR-PBCA-NPs) and to investigate the in vitro release charactersitics. VCR-PBCA-NPs were prepared by emulsion polymerization method, and characterized for morphology, particle size, drug encapsulation efficiency and loading efficiency. The formulation was optimized using central composite design and response surface methodology. In vitro release study of VCR-PBCA-NPs was performed by dialysis technique. Model fitting was used to determine the kinetics and to discuss the mechanism. The nanoparticles were spherical and uniform with a mean diameter of (98.9 +/- 3.05) nm. The drug encapsulation efficiency and loading efficiency were (55.23 +/- 0.96)% and (7.87 +/- 0.11)%, respectively. In vitro release results showed that 63.66% of VCR was released from VCR-PBCA-NPs in 4 h, and the Weibull model fitted VCR release pattern best. The VCR-PBCA-NPs prepared in this study showed sustained release compared with VCR solution.

Comparative Evaluation of Two Venous Sampling Techniques for the Assessment of Pancreatic Insulin and Zinc Release upon Glucose Challenge.

PubMed

Pillai, Anil Kumar; Silvers, William; Christensen, Preston; Riegel, Matthew; Adams-Huet, Beverley; Lingvay, Ildiko; Sun, Xiankai; Öz, Orhan K

2015-01-01

Advances in noninvasive imaging modalities have provided opportunities to study β cell function through imaging zinc release from insulin secreting β cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas.

Comparative Evaluation of Two Venous Sampling Techniques for the Assessment of Pancreatic Insulin and Zinc Release upon Glucose Challenge

PubMed Central

Pillai, Anil Kumar; Silvers, William; Christensen, Preston; Riegel, Matthew; Adams-Huet, Beverley; Lingvay, Ildiko; Sun, Xiankai; Öz, Orhan K.

2015-01-01

Advances in noninvasive imaging modalities have provided opportunities to study β cell function through imaging zinc release from insulin secreting β cells. Understanding the temporal secretory pattern of insulin and zinc corelease after a glucose challenge is essential for proper timing of administration of zinc sensing probes. Portal venous sampling is an essential part of pharmacological and nutritional studies in animal models. The purpose of this study was to compare two different percutaneous image-guided techniques: transhepatic ultrasound guided portal vein access and transsplenic fluoroscopy guided splenic vein access for ease of access, safety, and evaluation of temporal kinetics of insulin and zinc release into the venous effluent from the pancreas. Both techniques were safe, reproducible, and easy to perform. The mean time required to obtain desired catheter position for venous sampling was 15 minutes shorter using the transsplenic technique. A clear biphasic insulin release profile was observed in both techniques. Statistically higher insulin concentration but similar zinc release after a glucose challenge was observed from splenic vein samples, as compared to the ones from the portal vein. To our knowledge, this is the first report of percutaneous methods to assess zinc release kinetics from the porcine pancreas. PMID:26273676

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants

PubMed Central

Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2012-01-01

Purpose The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Methods Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT–Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0–5 mm) and horizontal (0–10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Results Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT–Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT–Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. Conclusion These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants. PMID:23028217

Characterization of drug-release kinetics in trabecular bone from titania nanotube implants.

PubMed

Aw, Moom Sinn; Khalid, Kamarul A; Gulati, Karan; Atkins, Gerald J; Pivonka, Peter; Findlay, David M; Losic, Dusan

2012-01-01

The aim of this study was to investigate the application of the three-dimensional bone bioreactor for studying drug-release kinetics and distribution of drugs in the ex vivo cancellous bone environment, and to demonstrate the application of nanoengineered titanium (Ti) wires generated with titania nanotube (TNT) arrays as drug-releasing implants for local drug delivery Nanoengineered Ti wires covered with a layer of TNT arrays implanted in bone were used as a drug-releasing implant. Viable bovine trabecular bone was used as the ex vivo bone substrate embedded with the implants and placed in the bone reactor. A hydrophilic fluorescent dye (rhodamine B) was used as the model drug, loaded inside the TNT-Ti implants, to monitor drug release and transport in trabecular bone. The distribution of released model drug in the bone was monitored throughout the bone structure, and concentration profiles at different vertical (0-5 mm) and horizontal (0-10 mm) distances from the implant surface were obtained at a range of release times from 1 hour to 5 days. Scanning electron microscopy confirmed that well-ordered, vertically aligned nanotube arrays were formed on the surface of prepared TNT-Ti wires. Thermogravimetric analysis proved loading of the model drug and fluorescence spectroscopy was used to show drug-release characteristics in-vitro. The drug release from implants inserted into bone ex vivo showed a consistent gradual release of model drug from the TNT-Ti implants, with a characteristic three-dimensional distribution into the surrounding bone, over a period of 5 days. The parameters including the flow rate of bone culture medium, differences in trabecular microarchitecture between bone samples, and mechanical loading were found to have the most significant influence on drug distribution in the bone. These results demonstrate the utility of the Zetos™ system for ex vivo drug-release studies in bone, which can be applied to optimize the delivery of specific therapies and to assist in the design of new drug delivery systems. This method has the potential to provide new knowledge to understand drug distribution in the bone environment and to considerably improve existing technologies for local administration in bone, including solving some critical problems in bone therapy and orthopedic implants.

Physicochemical aspects involved in methotrexate release kinetics from biodegradable spray-dried chitosan microparticles

NASA Astrophysics Data System (ADS)

Mesquita, Philippe C.; Oliveira, Alice R.; Pedrosa, Matheus F. Fernandes; de Oliveira, Anselmo Gomes; da Silva-Júnior, Arnóbio Antônio

2015-06-01

Spray dried methotrexate (MTX) loaded chitosan microparticles were prepared using different drug/copolymer ratios (9%, 18%, 27% and 45% w/w). The physicochemical aspects were assessed in order to select particles that were able to induce a sustained drug release effect. Particles were successfully produced which exhibited desired physicochemical aspects such as spherical shape and high drug loading. XRD and FT-IR analysis demonstrated that drug is not bound to copolymer and is only homogeneously dispersed in an amorphous state into polymeric matrix. Even the particles with higher drug loading levels presented a sustained drug release profile, which were mathematically modeled using adjusted Higuchi model. The drug release occurred predominantly with drug dissolution and diffusion through swollen polymeric matrix, with the slowest release occurring with particles containing 9% of drug, demonstrating an interesting and promising drug delivery system for MTX.

Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet.

PubMed

Bhalekar, M R; Madgulkar, A R; Sheladiya, D D; Kshirsagar, S J; Wable, N D; Desale, S S

2008-01-01

The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 3(2) full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X(1)) and bees wax (X(2)) were selected as independent variables and release after 12 h and time required for 50% (t(50)) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t(50) but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings.

Statistical Optimization of Sustained Release Venlafaxine HCI Wax Matrix Tablet

PubMed Central

Bhalekar, M. R.; Madgulkar, A. R.; Sheladiya, D. D.; Kshirsagar, S. J.; Wable, N. D.; Desale, S. S.

2008-01-01

The purpose of this research was to prepare a sustained release drug delivery system of venlafaxine hydrochloride by using a wax matrix system. The effects of bees wax and carnauba wax on drug release profile was investigated. A 32 full factorial design was applied to systemically optimize the drug release profile. Amounts of carnauba wax (X1) and bees wax (X2) were selected as independent variables and release after 12 h and time required for 50% (t50) drug release were selected as dependent variables. A mathematical model was generated for each response parameter. Both waxes retarded release after 12 h and increases the t50 but bees wax showed significant influence. The drug release pattern for all the formulation combinations was found to be approaching Peppas kinetic model. Suitable combination of two waxes provided fairly good regulated release profile. The response surfaces and contour plots for each response parameter are presented for further interpretation of the results. The optimum formulations were chosen and their predicted results found to be in close agreement with experimental findings. PMID:20046773

The influence of recrystallized caffeine on water-swellable polymethacrylate mucoadhesive buccal films.

PubMed

Morales, Javier O; Su, Rong; McConville, Jason T

2013-06-01

The aim of this work was to investigate the influence of particles on the properties of polymethacrylate films intended for buccal delivery. A solvent casting method was used with Eudragit RS and RL (ERS and ERL, respectively) as film-forming rate-controlling polymers, with caffeine as a water-soluble model drug. The physicochemical properties of the model films for a series of formulations with increasing concentrations of caffeine were determined in terms of morphology, mechanical and mucoadhesive properties, drug content uniformity, and drug release and associated kinetics. Typically regarded as non-mucoadhesive polymers, ERS and mainly ERL, were found to be good mucoadhesives, with ERL01 exhibiting a work of mucoadhesion (WoA) of 118.9 μJ, which was about five to six times higher than that observed for commonly used mucoadhesives such as Carbopol(®) 974P (C974P, 23.9 μJ) and polycarbophil (PCP, 17.4 μJ). The mucoadhesive force for ERL01 was found to be significantly lower yet comparable to C974P and PCP films (211.1 vs. 329.7 and 301.1 mN, respectively). Inspection of cross-sections of the films indicated that increasing the concentration of caffeine was correlated with the appearance of recrystallized agglomerates. In conclusion, caffeine agglomerates had detrimental effects in terms of mucoadhesion, mechanical properties, uniformity, and drug release at large particle sizes. ERL series of films exhibited very rapid release of caffeine while ERS series showed controlled release. Analysis of release profiles revealed that kinetics changed from a diffusion controlled to a first-order release mechanism.

Development and dissolution studies of bisphosphonate (clodronate)-containing hydroxyapatite-polylactic acid biocomposites for slow drug delivery.

PubMed

Macha, Innocent J; Cazalbou, Sophie; Shimmon, Ronald; Ben-Nissan, Besim; Milthorpe, Bruce

2017-06-01

An increase in clinical demand on the controlled release of bisphosphonates (BPs) due to complications associated with systemic administration, has been the current driving force on the development of BP drug-release systems. Bisphosphonates have the ability to bind to divalent metal ions, such as Ca 2+ , in bone mineral and prevent bone resorption by influencing the apoptosis of osteoclasts. Localized delivery using biodegradable materials, such as polylactic acid (PLA) and hydroxyapatite (HAp), which are ideal in this approach, have been used in this study to investigate the dissolution of clodronate (non-nitrogen-containing bisphosphonate) in a new release system. The effects of coral structure-derived HAp and the release kinetics of the composites were evaluated. The release kinetics of clodronate from PLA-BP and PLA-HAp-BP systems seemed to follow the power law model described by Korsmeyer-Peppas. Drug release was quantified by 31 P-NMR with detection and quantification limits of 9.2 and 30.7 mM, respectively. The results suggest that these biocomposite systems could be tuned to release clodronate for both relatively short and prolonged period of time. In addition to drug delivery, the degradation of HAp supplies both Ca 2+ and phosphate ions that can help in bone mineralization. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences.

PubMed

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug-fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug-fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid.

The load and release characteristics on a strong cationic ion-exchange fiber: kinetics, thermodynamics, and influences

PubMed Central

Yuan, Jing; Gao, Yanan; Wang, Xinyu; Liu, Hongzhuo; Che, Xin; Xu, Lu; Yang, Yang; Wang, Qifang; Wang, Yan; Li, Sanming

2014-01-01

Ion-exchange fibers were different from conventional ion-exchange resins in their non-cross-linked structure. The exchange was located on the surface of the framework, and the transport resistance reduced significantly, which might mean that the exchange is controlled by an ionic reaction instead of diffusion. Therefore, this work aimed to investigate the load and release characteristics of five model drugs with the strong cationic ion-exchange fiber ZB-1. Drugs were loaded using a batch process and released in United States Pharmacopoeia (USP) dissolution apparatus 2. Opposing exchange kinetics, suitable for the special structure of the fiber, were developed for describing the exchange process with the help of thermodynamics, which illustrated that the load was controlled by an ionic reaction. The molecular weight was the most important factor to influence the drug load and release rate. Strong alkalinity and rings in the molecular structures made the affinity between the drug and fiber strong, while logP did not cause any profound differences. The drug–fiber complexes exhibited sustained release. Different kinds and concentrations of counter ions or different amounts of drug–fiber complexes in the release medium affected the release behavior, while the pH value was independent of it. The groundwork for in-depth exploration and further application of ion-exchange fibers has been laid. PMID:25114504

Controlling of free radical copolymerization of styrene and maleic anhydride via RAFT process for the preparation of acetaminophen drug conjugates

NASA Astrophysics Data System (ADS)

Sütekin, S. Duygu; Atıcı, Ayşe Bakar; Güven, Olgun; Hoffman, Allan S.

2018-07-01

The presence of maleic anhydride moiety in styrene-maleic anhydride (SMA) copolymer makes it a versatile substrate for conjugation of drugs. In this study biocompatible styrene-maleic anhydride (SMA) copolymer with alternating structure was synthesized by gamma irradiation at room temperature in the presence of 2-phenyl-2-propyl benzodithioate (PPB). The poly(styrene-alt-maleic anhydride) (poly(St-alt-MA)) with narrow molecular weight distribution (Đ: 1.1-1.3) was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization. The synthesized poly(St-alt-MA) structure was characterized by ATR-FTIR spectroscopy, elemental analysis and 1H NMR spectroscopy and molecular weight and dispersity were determined by size exclusion chromatography (SEC). SMA copolymers were further conjugated with acetaminophen via ester linkage and FT-IR, 1H NMR investigation indicated that the acetaminophen was attached to poly(St-alt-MA). Drug release profile of the polymer-drug conjugate was followed by high performance liquid chromatography (HPLC). The drug-conjugate system was found to follow first order release kinetics with Hixson-Crowell model while drug release mechanism was found as non-Fickian diffusion after testing various kinetic models.

Water-in-Water Emulsion Based Synthesis of Hydrogel Nanospheres with Tunable Release Kinetics

NASA Astrophysics Data System (ADS)

Aydın, Derya; Kızılel, Seda

2017-07-01

Poly(ethylene glycol) (PEG) micro/nanospheres have several unique advantages as polymer based drug delivery systems (DDS) such as tunable size, large surface area to volume ratio, and colloidal stability. Emulsification is one of the widely used methods for facile synthesis of micro/nanospheres. Two-phase aqueous system based on polymer-polymer immiscibility is a novel approach for preparation of water-in-water (w/w) emulsions. This method is promising for the synthesis of PEG micro/nanospheres for biological systems, since the emulsion is aqueous and do not require organic solvents or surfactants. Here, we report the synthesis of nano-scale PEG hydrogel particles using w/w emulsions using phase separation of dextran and PEG prepolymer. Dynamic light scattering (DLS) and scaning electron microscopy (SEM) results demonstrated that nano-scale hydrogel spheres could be obtained with this approach. We investigated the release kinetics of a model drug, pregabalin (PGB) from PEG nanospheres and demonstrated the influence of polymerization conditions on loading and release of the drug as well as the morphology and size distribution of PEG nanospheres. The experimental drug release data was fitted to a stretched exponential function which suggested high correlation with experimental results to predict half-time and drug release rates from the model equation. The biocompatibility of nanospheres on human dermal fibroblasts using cell-survival assay suggested that PEG nanospheres with altered concentrations are non-toxic, and can be considered for controlled drug/molecule delivery.

Hydrolysis kinetics of secoisolariciresinol diglucoside oligomers from flaxseed.

PubMed

Yuan, Jian-Ping; Li, Xin; Xu, Shi-Ping; Wang, Jiang-Hai; Liu, Xin

2008-11-12

Flaxseed is the richest dietary source of the lignan secoisolariciresinol diglucoside (SDG) and contains the largest amount of SDG oligomers, which are often hydrolyzed to break the ester linkages for the release of SDG and the glycosidic bonds for the release of secoisolariciresinol (SECO). The alkaline hydrolysis reaction kinetics of SDG oligomers from flaxseed and the acid hydrolysis process of SDG and other glucosides were investigated. For the kinetic modeling, a pseudo-first-order reaction was assumed. The results showed that the alkaline hydrolysis of SDG oligomers followed first-order reaction kinetics under mild alkaline hydrolytic conditions and that the concentration of sodium hydroxide had a strong influence on the activation energy of the alkaline hydrolysis of SDG oligomers. The results also indicated that the main acid hydrolysates of SDG included secoisolariciresinol monoglucoside (SMG), SECO, and anhydrosecoisolariciresinol (anhydro-SECO) and that the extent and the main hydrolysates of the acid hydrolysis reaction depended on the acid concentration, hydrolysis temperature, and time. In addition, the production and change of p-coumaric acid glucoside, ferulic acid glucoside and their methyl esters and p-coumaric acid, ferulic acid, and their methyl esters during the process of hydrolysis was also investigated.

Energy release estimation for fragmenting meteoroid

NASA Astrophysics Data System (ADS)

Egorova, L. A.; Lokhin, V. V.

2018-05-01

It is known that for the adequate interpretation of fireball observations it is necessary to take into account its fragmentation in the Earth's atmosphere. Various models for large cosmic body destruction in the atmosphere are known. Presented work continues our previous research on the fragmentation of fireballs. Proposing a model for the destruction of a fireball we also submit a model for the transition of its kinetic energy to thermal one. The meteoroid destruction under consideration is similar to the destruction of a solid body during an explosion. The kinetic energy of the moving particles of the crashing meteoric body transform into the thermal energy of the gas volume in which their motion occurs.

Exhaustive Exercise-induced Oxidative Stress Alteration of Erythrocyte Oxygen Release Capacity.

PubMed

Xiong, Yanlian; Xiong, Yanlei; Wang, Yueming; Zhao, Yajin; Li, Yaojin; Ren, Yang; Wang, Ruofeng; Zhao, Mingzi; Hao, Yitong; Liu, Haibei; Wang, Xiang

2018-05-24

The aim of the present study is to explore the effect of exhaustive running exercise (ERE) in the oxygen release capacity of rat erythrocytes. Rats were divided into sedentary control (C), moderate running exercise (MRE) and exhaustive running exercise groups. The thermodynamics and kinetics properties of the erythrocyte oxygen release process of different groups were tested. We also determined the degree of band-3 oxidative and phosphorylation, anion transport activity and carbonic anhydrase isoform II(CAII) activity. Biochemical studies suggested that exhaustive running significantly increased oxidative injury parameters in TBARS and methaemoglobin levels. Furthermore, exhaustive running significantly decreased anion transport activity and carbonic anhydrase isoform II(CAII) activity. Thermodynamic analysis indicated that erythrocytes oxygen release ability also significantly increased due to elevated 2,3-DPG level after exhaustive running. Kinetic analysis indicated that exhaustive running resulted in significantly decreased T50 value. We presented evidence that exhaustive running remarkably impacted thermodynamics and kinetics properties of RBCs oxygen release. In addition, changes in 2,3-DPG levels and band-3 oxidation and phosphorylation could be the driving force for exhaustive running induced alterations in erythrocytes oxygen release thermodynamics and kinetics properties.

Prediction of heat release effects on a mixing layer

NASA Technical Reports Server (NTRS)

Farshchi, M.

1986-01-01

A fully second-order closure model for turbulent reacting flows is suggested based on Favre statistics. For diffusion flames the local thermodynamic state is related to single conserved scalar. The properties of pressure fluctuations are analyzed for turbulent flows with fluctuating density. Closure models for pressure correlations are discussed and modeled transport equations for Reynolds stresses, turbulent kinetic energy dissipation, density-velocity correlations, scalar moments and dissipation are presented and solved, together with the mean equations for momentum and mixture fraction. Solutions of these equations are compared with the experimental data for high heat release free mixing layers of fluorine and hydrogen in a nitrogen diluent.

Investigating the Release of a Hydrophobic Peptide from Matrices of Biodegradable Polymers: An Integrated Method Approach

PubMed Central

Gubskaya, Anna V.; Khan, I. John; Valenzuela, Loreto M.; Lisnyak, Yuriy V.; Kohn, Joachim

2013-01-01

The objectives of this work were: (1) to select suitable compositions of tyrosine-derived polycarbonates for controlled delivery of voclosporin, a potent drug candidate to treat ocular diseases, (2) to establish a structure-function relationship between key molecular characteristics of biodegradable polymer matrices and drug release kinetics, and (3) to identify factors contributing in the rate of drug release. For the first time, the experimental study of polymeric drug release was accompanied by a hierarchical sequence of three computational methods. First, suitable polymer compositions used in subsequent neural network modeling were determined by means of response surface methodology (RSM). Second, accurate artificial neural network (ANN) models were built to predict drug release profiles for fifteen polymers located outside the initial design space. Finally, thermodynamic properties and hydrogen-bonding patterns of model drug-polymer complexes were studied using molecular dynamics (MD) technique to elucidate a role of specific interactions in drug release mechanism. This research presents further development of methodological approaches to meet challenges in the design of polymeric drug delivery systems. PMID:24039300

Wax-based sustained release matrix pellets prepared by a novel freeze pelletization technique II. In vitro drug release studies and release mechanisms.

PubMed

Cheboyina, Sreekhar; Wyandt, Christy M

2008-07-09

A novel freeze pelletization technique was evaluated for the preparation of wax-based sustained release matrix pellets. Pellets containing water-soluble drugs were successfully prepared using a variety of waxes. The drug release significantly depended on the wax type used and the aqueous drug solubility. The drug release decreased as the hydrophobicity of wax increased and the drug release increased as the aqueous drug solubility increased. In glyceryl monostearate (GMS) pellets, drug release rate decreased as the loading of theophylline increased. On the contrary, the release rate increased as the drug loading of diltiazem HCl increased in Precirol pellets. Theophylline at low drug loads existed in a dissolved state in GMS pellets and the release followed desorption kinetics. At higher loads, theophylline existed in a crystalline state and the release followed dissolution-controlled constant release for all the waxes studied. However, with the addition of increasing amounts of Brij 76, theophylline release rate increased and the release mechanism shifted to diffusion-controlled square root time kinetics. But the release of diltiazem HCl from Precirol pellets at all drug loads, followed diffusion-controlled square root time kinetics. Therefore, pellets capable of providing a variety of release profiles for different drugs can be prepared using this freeze pelletization technique by suitably modifying the pellet forming matrix compositions.

Chitosan Nanofibers for Transbuccal Insulin Delivery

PubMed Central

Lancina, Michael G.; Shankar, Roopa Kanakatti; Yang, Hu

2017-01-01

Purpose In this work, we aimed at producing chitosan based nanofiber mats capable of delivering insulin via the buccal mucosa. Methods Chitosan was electrospun into nanofibers using poly (ethylene oxide) (PEO) as a carrier molecule in various feed ratios. The mechanical properties and degradation kinetics of the fibers were measured. Insulin release rates were determined in vitro using an ELISA assay. The bioactivity of released insulin was measured in terms of Akt activation in pre-adipocytes. Insulin permeation across the buccal mucosa was measured in an ex-vivo porcine transbuccal model. Results Fiber morphology, mechanical properties, and in vitro stability were dependent on PEO feed ratio. Lower PEO content blends produced smaller diameter fibers with significantly faster insulin release kinetics. Insulin showed no reduction in bioactivity due to electrospinning. Buccal permeation of insulin facilitated by high chitosan content blends was significantly higher than that of free insulin. Conclusions Taken together, our work demonstrates chitosan based nanofibers have the potential to serve as a transbuccal insulin delivery vehicle. PMID:28000386

Heparin-based hydrogels with tunable sulfation & degradation for anti-inflammatory small molecule delivery.

PubMed

Peng, Yifeng; Tellier, Liane E; Temenoff, Johnna S

2016-08-16

Sustained release of anti-inflammatory agents remains challenging for small molecule drugs due to their low molecular weight and hydrophobicity. Therefore, the goal of this study was to control the release of a small molecule anti-inflammatory agent, crystal violet (CV), from hydrogels fabricated with heparin, a highly sulfated glycosaminoglycan capable of binding positively-charged molecules such as CV. In this system, both electrostatic interactions between heparin and CV and hydrogel degradation were tuned simultaneously by varying the level of heparin sulfation and varying the amount of dithiothreitol within hydrogels, respectively. It was found that heparin sulfation significantly affected CV release, whereby more sulfated heparin hydrogels (Hep and Hep(-N)) released CV with near zero-order release kinetics (R-squared values between 0.96-0.99). Furthermore, CV was released more quickly from fast-degrading hydrogels than slow-degrading hydrogels, providing a method to tune total CV release between 5-15 days while maintaining linear release kinetics. In particular, N-desulfated heparin hydrogels exhibited efficient CV loading (∼90% of originally included CV), near zero-order CV release kinetics, and maintenance of CV bioactivity after release, making this hydrogel formulation a promising CV delivery vehicle for a wide range of inflammatory diseases.

Thermogravimetric analysis for the determination of water release rate from microcrystalline cellulose dry powder and wet bead systems.

PubMed

Mayville, Francis C; Wigent, Rodney J; Schwartz, Joseph B

2006-01-01

The purpose of this work was to determine the total amount of water contained in dry powder and wet bead samples of microcrystalline cellulose, MCC, (Avicel PH-101), taken from various stages of the extrusion/marumerization process used to make beads and to determine the kinetic rates of water release from each sample. These samples were allowed to equilibrate in controlled humidity chambers at 25 degrees C. The total amount of water in each sample, after equilibration, was determined by thermogravimetric analysis (TGA) as a function of temperature. The rates of water release from these samples were determined by using isothermal gravimetric analysis (ITGA) as a function of time. Analysis of the results for these studies suggest that water was released from these systems by several different kinetic mechanisms. The water release mechanisms for these systems include: zero order, second order, and diffusion controlled kinetics. It is believed that all three kinetic mechanisms will occur at the same time, however; only one mechanism will be prominent. The prominent mechanism was based on the amount of water present in the sample.

Exposure of Microcystis aeruginosa to hydrogen peroxide and titanium dioxide under visible light conditions: Modeling the impact of hydrogen peroxide and hydroxyl radical on cell rupture and microcystin degradation.

PubMed

Chang, Che-Wei; Huo, Xiangchen; Lin, Tsair-Fuh

2018-05-14

The aims of this study are to evaluate, under visible light conditions, the ability of H 2 O 2 and TiO 2 to produce OH, their quantitative impacts on the cell integrity of Microcystis, and the subsequent release and degradation of microcystins (MCs). A sequential reaction model was developed, including one sub-model to simulate the rupture kinetics for cell integrity of Microcystis, and another to describe the release and degradation of MCs. For cell rupture, the dual-oxidant Delayed Chick-Watson model (DCWM) and dual-oxidant Hom model (HM) were first proposed and developed, giving excellent simulation results of cell rupture kinetics. Kinetic rate constants between Microcystis cells and H 2 O 2 [Formula: see text] as well as OH (k •OH, Cell ) under visible light successfully separated the individual effects of H 2 O 2 and OH on Microcystis. The dual-oxidant models were further validated with additional experiments, making the models more convincing. Finally, the dual-oxidant cell rupture models were integrated with the MC degradation model and well predicted the observed MCs concentrations in the experimental systems. The results of this study not only demonstrate the potential application of H 2 O 2 and TiO 2 for the control of cyanobacteria and metabolites in natural water bodies, but also provide a new methodology to differentiate the individual contributions of the two oxidants, H 2 O 2 and OH, on cell rupture, thus giving a novel way to more precisely determine the effective doses of applied oxidants for cyanobacteria control. Copyright © 2018 Elsevier Ltd. All rights reserved.

Micro- and Nano-scale Diffusion Domains Acting as Kinetic Controls for U(VI) Release to the Hanford 300-Area Aquifer

NASA Astrophysics Data System (ADS)

Stoliker, D. L.; Hay, M. B.; Davis, J. A.; Zachara, J. M.

2008-12-01

The 300-Area of the Hanford reservation, a cold-war era nuclear processing facility, is plagued by long-term elevated concentrations of U(VI) in the underlying aquifer. While the sediment U(VI) concentration is relatively low, it continues to act as a source and sink for the contaminant, allowing for persistent groundwater concentrations well above the maximum contamination limit (MCL). Simple Kd modeling of the attenuation of U(VI) in the aquifer predicted that groundwater U(VI) concentrations would decrease to below the drinking water standard by the year 2002. However, grain-scale morphology of the aquifer material suggests that intra-grain flow paths and mineral coatings, in which sorption complexes and precipitates formed over years of waste disposal, provide a significant kinetic constraint that slows groundwater flushing of the sediments. In order to quantify the impact of diffusion kinetics on the release of U(VI), high-resolution, non-reactive tracer studies were conducted on vadose zone sediments in both column and batch reactors. Systems were equilibrated for long time scales with tritated artificial groundwater and then flushed with flow and stop-flow events included for columns. Previously collected U(VI) release data from batch dissolution/desorption studies is compared with tritium tracer diffusion kinetics as well as porosimetry and detailed microscopy characterization. The micro-scale and nano-scale diffusion regimes, including intra-granular regions as well as mineral coatings, represent a significant potential long-term source of contaminant U(VI). Understanding the physical kinetic limitations coupled with the complex chemistry of U(VI) sorption processes within natural systems is an important step forward in providing information to strengthen field-scale reactive transport simulations.

The total kinetic energy release in the fast neutron-induced fission of 232Th

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

King, Jonathan; Yanez, Ricardo; Loveland, Walter

Here, the post-emission total kinetic energy release (TKE) in the neutron-induced fission of 232Th was measured (using white spectrum neutrons from LANSCE) for neutron energies from E n=3 to 91MeV. In this energy range the average post-neutron total kinetic energy release decreases from 162.3±0.3 at E n=3 MeV to 154.9±0.3 MeV at E n=91 MeV. Analysis of the fission mass distributions indicates that the decrease in TKE with increasing neutron energy is a combination of increasing yields of symmetric fission (which has a lower associated TKE) and a decrease in the TKE release in asymmetric fission.

The total kinetic energy release in the fast neutron-induced fission of 232Th

DOE PAGES

King, Jonathan; Yanez, Ricardo; Loveland, Walter; ...

2017-12-15

Here, the post-emission total kinetic energy release (TKE) in the neutron-induced fission of 232Th was measured (using white spectrum neutrons from LANSCE) for neutron energies from E n=3 to 91MeV. In this energy range the average post-neutron total kinetic energy release decreases from 162.3±0.3 at E n=3 MeV to 154.9±0.3 MeV at E n=91 MeV. Analysis of the fission mass distributions indicates that the decrease in TKE with increasing neutron energy is a combination of increasing yields of symmetric fission (which has a lower associated TKE) and a decrease in the TKE release in asymmetric fission.

Silver nanoparticles in aquatic environments: Physiochemical behavior and antimicrobial mechanisms.

PubMed

Zhang, Chiqian; Hu, Zhiqiang; Deng, Baolin

2016-01-01

Nanosilver (silver nanoparticles or AgNPs) has unique physiochemical properties and strong antimicrobial activities. This paper provides a comprehensive review of the physicochemical behavior (e.g., dissolution and aggregation) and antimicrobial mechanisms of nanosilver in aquatic environments. The inconsistency in calculating the Gibbs free energy of formation of nanosilver [ΔGf(AgNPs)] in aquatic environments highlights the research needed to carefully determine the thermodynamic stability of nanosilver. The dissolutive release of silver ion (Ag(+)) in the literature is often described using a pseudo-first-order kinetics, but the fit is generally poor. This paper proposes a two-stage model that could better predict silver ion release kinetics. The theoretical analysis suggests that nanosilver dissolution could occur under anoxic conditions and that nanosilver may be sulfidized to form silver sulfide (Ag2S) under strict anaerobic conditions, but more investigation with carefully-designed experiments is required to confirm the analysis. Although silver ion release is likely the main antimicrobial mechanism of nanosilver, the contributions of (ion-free) AgNPs and reactive oxygen species (ROS) generation to the overall toxicity of nanosilver must not be neglected. Several research directions are proposed to better understand the dissolution kinetics of nanosilver and its antimicrobial mechanisms under various aquatic environmental conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preparation of Monodisperse Biodegradable Polymer Microparticles Using a Microfluidic Flow-focusing Device for Controlled Drug Delivery

PubMed Central

Xu, Qiaobing; Hashimoto, Michinao; Dang, Tram T.; Hoare, Todd; Kohane, Daniel S.; Whitesides, George M.; Langer, Robert; Anderson, Daniel G.

2009-01-01

Degradable microparticles have broad utility as vehicles for drug delivery and form the basis of several FDA-approved therapies. Conventional emulsion-based methods of manufacturing produce particles with a wide range of diameters (and thus kinetics of release) in each batch. This paper describes the fabrication of monodisperse, drug-loaded microparticles from biodegradable polymers using the microfluidic flow-focusing (FF) devices and the drug delivery properties of those particles. Particles were engineered with defined sizes, ranging from 10 μm to 50 μm. These particles were nearly monodisperse (polydispersity index = 3.9 %). We incorporated a model amphiphilic drug (bupivacaine) within the biodegradable matrix of the particles. Kinetic analysis showed that the release of drug from these monodisperse particles was slower than that from conventional methods of the same average size but a broader distribution of sizes and, most importantly, exhibited a significantly lower initial burst than that observed with conventional particles. The difference in the initial kinetics of drug release was attributed to the uniform distribution of drug inside the particles generated using the microfluidic methods. These results demonstrated the utility of microfluidic FF for the generation of homogenous systems of particles for the delivery of drugs. PMID:19296563

Films based on soy protein-agar blends for wound dressing: Effect of different biopolymer proportions on the drug release rate and the physical and antibacterial properties of the films.

PubMed

Rivadeneira, Josefina; Audisio, M C; Gorustovich, Alejandro

2018-04-01

No single material can provide all requirements for wound dressings. Here, we evaluated the influence of different soy protein isolate and agar proportions (3:1, 1:1, and 1:3) in blend films on some of their physical-chemical and antibacterial properties to elucidate their potential as wound dressings. The films were synthesized by the gel casting method and ciprofloxacin hydrochloride was incorporated into the films. Films were characterized based on their surface morphology, water uptake ability, and weight loss profile. Also, the ciprofloxacin hydrochloride release kinetics was quantified spectrophotometrically. The antibacterial effect was evaluated against Staphylococcus aureus and Pseudomonas aeruginosa strains. The soy protein isolate-agar ratio affected the water uptake of the films and the release profile of ciprofloxacin hydrochloride but not the weight loss profile. The amount of drug released decreased near 80% because of the decrease in agar content in the films. The release kinetics of ciprofloxacin hydrochloride data best fitted to the Korsmeyer-Peppas model, suggesting that the mechanism of drug release was mainly of the diffusion type. All ciprofloxacin hydrochloride-releasing soy protein isolate-agar films strongly inhibited the cell viability of the bacterial strains studied. We concluded that water uptake and ciprofloxacin hydrochloride release can be controlled by changing the soy protein isolate-agar proportion. The proportions did not lead to changes in the antibacterial strength of the films.

Mechanism and Kinetics of Inducible Nitric Oxide Synthase Auto-S-Nitrosation and Inactivation†

PubMed Central

Smith, Brian C.; Fernhoff, Nathaniel B.; Marletta, Michael A.

2012-01-01

Nitric oxide (NO), the product of the nitric oxide synthase (NOS) reaction, was previously shown to result in S-nitrosation of the NOS Zn2+-tetrathiolate and inactivation of the enzyme. To probe the potential physiological significance of NOS S-nitrosation, the inactivation timescale of the inducible NOS isoform (iNOS) was determined and found to directly correlate with an increase in iNOS S-nitrosation. A kinetic model of NOS inactivation in which arginine is treated as a suicide substrate was developed. In this model, NO synthesized at the heme cofactor is partitioned between release into solution (NO release pathway) and NOS S-nitrosation followed by NOS inactivation (inactivation pathway). Experimentally determined progress curves of NO formation were fit to the model. The NO release pathway was perturbed through addition of the NO traps oxymyoglobin (MbO2) and β2 H-NOX, which yielded partition ratios between NO release and inactivation of ~100 at 4 μM MbO2 and ~22,000 at saturating trap concentrations. The results suggest that a portion of the NO synthesized at the heme cofactor reacts with the Zn2+-tetrathiolate without being released into solution. Perturbation of the inactivation pathway through addition of the reducing agents GSH or TCEP resulted in a concentration-dependent decrease in iNOS S-nitrosation that directly correlated with protection from iNOS inactivation. iNOS inactivation was most responsive to physiological concentrations of GSH with an apparent Km value of 13 mM. NOS turnover that leads to NOS S-nitrosation might be a mechanism to control NOS activity, and NOS S-nitrosation could play a role in the physiological generation of nitrosothiols. PMID:22242685

Microparticulate drug delivery system containing tramadol hydrochloride for pain treatment.

PubMed

Ciurba, Adriana; Todoran, Nicoleta; Vari, C E; Lazăr, Luminita; Al Hussein, Stela; Hancu, G

2014-01-01

The current trend of replacing conventional pharmaceutical forms is justified because most substances administered in this form give fluctuations of therapeutic concentrations and often outside the therapeutic range. In addition, these formulations offer a reduction in the dose or the number of administrations, thus increasing patient compliance. In the experiment, we developed an appropriate technology for the preparation of gelatin microspheres containing tramadol hydrochloride by emulsification/cross-linking method. The formulated microspheres were characterized by product yield, size distribution, encapsulation efficiency and in vitro release of tramadol hydrochloride. Data obtained from in vitro release studies were fitted to various mathematical models to elucidate the transport mechanisms. The kinetic models used were zero-order, first-order, Higuchi Korsmeyer-Peppas and Hopfenberg. Spherical microspheres were obtained, with free-flowing properties. The entrapment efficiency of tramadol hydrochloride in microparticles was 79.91% and product yield -94.92%. As the microsphere size was increased, the entrapment efficiency increased. This was 67.56, 70.03, 79.91% for formulations MT80-250, MT8-500 and, MT250-500. High entrapment efficiency was observed for MT250-500 formulation. The gelatin microspheres had particle sizes ranging from 80 to 500 microm. The drug was released for a period of 12 hours with a maximum release of 96.02%. Of the three proposed formulations, MT250-500 presented desirable properties and optimal characteristics for the therapy of pain. Release of tramadol hydrochloridi was best fitted to Korsmeyer-Peppas equation because the Akaike Information Criterion had the lowest values for this kinetic model. These results suggest the opportunity to influence the therapeutic characteristics of gelatin microspheres to obtain a suitable drug delivery system for the oral administration of tramadol hydrochloride.

IVABRADINE LOADED SOLID LIPID MICROPARTICLES: FORMULATION, CHARACTERIZATION AND OPTIMIZATION BY CENTRAL COMPOSITE ROTATABLE DESIGN.

PubMed

Hanif, Muhammad; Khan, Hafeez Ullah; Afzal, Samina; Sher, Muhammad

2017-01-01

The current research focused on improvement of oral bioavailability and decrease in dosing frequency of ivabradine (Iva) in order to enhance patient compliance by formulating novel sustained release Iva loaded solid lipid microparticles (SLMs) with the help of melt emulsification technique. SLMs formulations were designed with the help of three level central composite rotatable design (CCRD) to study the impact of independent variables like lipid concentration, surfactant concentration and stirring speed on responses - percentage yield (Y,) and entrapment efficiency (Y2). Compatibility between the drug and bees wax (BW) was checked by conducting Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD). SLMs were further evaluated for rheological behavior, zeta potential, particle size and for morphology by scanning'electron microscope (SEM). The release of drug from SLMs was conducted by USP type-Il apparatus at pH 1.2, pH 6.8 and data were analyzed by different kinetic models like zero order, first order, Higuchi model, Korsmeyer-Peppas and Hixon-Crowell models. The rheo- logical studies approved the good flow behavior of SLMs and spherical smooth surface of SLMs was observed from SEM. DSC, FTIR and XRD studies concluded the lack of any possible interaction between formulation components. The size-of SLMs ranged from 300 to 500 pm and zeta potential study showed the presence of higher negative charge (-30 to -52 mV). Response Y, varied from 53 to 90% and response Y2 ranged from 29 to 78% indicating the effect of formulation variables. The obtained outcomes were analyzed by second order polynomial equation and suggested quadratic model was also validated. SLMs released Iva from 54 to 90% at pH 6.8 and was significantly (p 0.05) affected by BW concentration. The release mechanism followed the zero order and Korsmeyer-Peppas (n 0.85) kinetic models suggesting slow erosion along with diffusion mechanism for Iva release.

Regulating Drug Release Behavior and Kinetics from Matrix Tablets Based on Fine Particle-Sized Ethyl Cellulose Ether Derivatives: An In Vitro and In Vivo Evaluation

PubMed Central

Shah, Kifayat Ullah; Khan, Gul Majid

2012-01-01

The design and fabrication of sustained/controlled release dosage forms, employing new excipients capable of extending/controlling the release of drugs from the dosage forms over prolonged periods, has worked well in achieving optimally enhanced therapeutic levels of the drugs. In this sense, the objective of this study was to investigate the suitability of selected cellulose ether derivatives for use in direct compression (DC) and as efficient drug release controlling agents. Controlled release matrix tablets of ciprofloxacin were prepared at different drug-to-polymer (D : P) ratios by direct compression using a fine particle sized ethylcellulose ether derivative (ETHOCEL Standard Premium 7FP) as rate controlling polymer. The tablets obtained were evaluated for various physico-chemical characteristics and in-vitro drug release studies were conducted in phosphate buffer (pH 7.4) using PharmaTest dissolution apparatus at constant temperature of 37°C ± 0.1. Similarity factor f 2 was employed to the release profiles of test formulations and were compared with marketed ciprofloxacin conventional tablets. Drug release mechanism and the kinetics involved were investigated by fitting the release profile data to various kinetic models. It was found that with increasing the proportion of ethylcellulose ether derivative in the matrix, the drug release was significantly extended up to 24 hours. The tablets exhibited zero order or nearly zero order drug transport mechanism. In vivo drug release performance of the developed controlled release tablets and reference conventional tablets containing ciprofloxacin were determined in rabbit serum according to randomized two-way crossover study design using High Performance Liquid Chromatography. Several bioavailability parameters of both the test tablets and conventional tablets including C max⁡, T max⁡ and AUC0-t were compared which showed an optimized C max⁡ and T max⁡ (P < 0.05). A good correlation was obtained between in vitro drug release and in vivo drug absorption with correlation value (R 2 = 0.934). Relative bioavailability was found to be 93%. Reproducibility of manufacturing process and accelerated stability of the developed tablets were performed in stability chamber at 40 ± 2°C and 75 ± 5% relative humidity for a period of 6 months and were found to be stable throughout the stability period. PMID:22649325

A mathematical model for interpreting in vitro rhGH release from laminar implants.

PubMed

Santoveña, A; García, J T; Oliva, A; Llabrés, M; Fariña, J B

2006-02-17

Recombinant human growth hormone (rhGH), used mainly for the treatment of growth hormone deficiency in children, requires daily subcutaneous injections. The use of controlled release formulations with appropriate rhGH release kinetics reduces the frequency of medication, improving patient compliance and quality of life. Biodegradable implants are a valid alternative, offering the feasibility of a regular release rate after administering a single dose, though it exists the slight disadvantage of a very minor surgical operation. Three laminar implant formulations (F(1), F(2) and F(3)) were produced by different manufacture procedures using solvent-casting techniques with the same copoly(D,L-lactic) glycolic acid (PLGA) polymer (Mw=48 kDa). A correlation in vitro between polymer matrix degradation and drug release rate from these formulations was found and a mathematical model was developed to interpret this. This model was applied to each formulation. The obtained results where explained in terms of manufacture parameters with the aim of elucidate whether drug release only occurs by diffusion or erosion, or by a combination of both mechanisms. Controlling the manufacture method and the resultant changes in polymer structure facilitates a suitable rhGH release profile for different rhGH deficiency treatments.

Intestine-Specific, Oral Delivery of Captopril/Montmorillonite: Formulation and Release Kinetics

PubMed Central

2011-01-01

The intercalation of captopril (CP) into the interlayers of montmorillonite (MMT) affords an intestine-selective drug delivery system that has a captopril-loading capacity of up to ca. 14 %w/w and which exhibits near-zero-order release kinetics. PMID:27502639

Kinetics for the distribution of acrylamide in French fries, fried oil and vapour during frying of potatoes.

PubMed

Hsu, Hui-Tsung; Chen, Ming-Jen; Tseng, Tzu-Ping; Cheng, Li-Hsin; Huang, Li-Jen; Yeh, Tai-Sheng

2016-11-15

Kinetic analysis for the formation of acrylamide in heated foods has been typically performed using only measured data of acrylamide in foods; however, its possible loss caused by release from heated foods into fried oil and air has seldom been considered. The results obtained from the monitoring of acrylamide by frying French fries indicated that acrylamide is distributed in three phases: French fries, frying oil, and air. From the evolved gas analysis of acrylamide and the measured concentration profile of the total acrylamide amount present in these phases, the kinetic behaviour for acrylamide formation does not obey the commonly used model of two-step consecutive reactions during frying, while a lumped kinetic model was proposed for the total acrylamide amount. Moreover, a high acrylamide level in air was observed, implying that, apart from consumers of French fries, fast-food restaurant workers are potentially subject to occupational hazards from acrylamide inhalation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of functional properties and release kinetics on antioxidant activity of biopolymer active films and coatings.

PubMed

Benbettaïeb, Nasreddine; Tanner, Cadhla; Cayot, Philippe; Karbowiak, Thomas; Debeaufort, Frédéric

2018-03-01

This work deals with the study of the release kinetics of some natural antioxidants (ferulic acid, caffeic acid and tyrosol) from chitosan-fish gelatin edible films immersed ethanol at 96%, as well as the kinetics of their antioxidant activity using the DPPH assay. The aim was to determine how film functional properties influence the release kinetic and antioxidant activity. The addition of antioxidants to chitosan-fish gelatin matrix decreased the water vapour permeability by more than 30%. The tensile strength (TS) increased up to 50% after the incorporation of antioxidants. Some molecular interactions between polymer chains and antioxidants were confirmed by FTIR where spectra displayed a shift of the amide-III peak. Films containing caffeic acid or a caffeic-ferulic acid mixture exhibited the highest radical scavenging activity, leading to a 90% antioxidant activity at equilibrium but the release rate controlled the efficacy of the system. Copyright © 2017 Elsevier Ltd. All rights reserved.

Formulation, in vitro evaluation and kinetic analysis of chitosan-gelatin bilayer muco-adhesive buccal patches of insulin nanoparticles.

PubMed

Mahdizadeh Barzoki, Zahra; Emam-Djomeh, Zahra; Mortazavian, Elaheh; Akbar Moosavi-Movahedi, Ali; Rafiee Tehrani, M

2016-11-01

The present study was performed to optimise the formulation of a muco-adhesive buccal patch for insulin nanoparticles (NPs) delivery. Insulin NPs were synthesised by an ionic gelation technique using N-di methyl ethyl chitosan cysteine (DMEC-Cys) as permeation enhancer biopolymer, tripolyphosphate (TPP) and insulin. Buccal patches were developed by solvent-casting technique using chitosan and gelatine as muco-adhesive polymers. Optimised patches were embedded with 3 mg of insulin-loaded NPs with a homogeneous distribution of NPs in the muco-adhesive matrix, which displayed adequate physico-mechanical properties. The drug release characteristics, release mechanism and kinetics were investigated. Data fitting to Peppas equation with a correlation coefficient indicated that the mechanism of drug release followed an anomalous transport that means drug release was afforded through drug diffusion along with polymer erosion. In vitro drug release, release kinetics, physical and mechanical studies for all patch formulations reflected the ideal characteristics of this buccal patch for the delivery of insulin NPs.

Oxaliplatin loaded PLAGA microspheres: design of specific release profiles.

PubMed

Lagarce, F; Cruaud, O; Deuschel, C; Bayssas, M; Griffon-Etienne, G; Benoit, J

2002-08-21

Oxaliplatin loaded PLAGA microspheres have been prepared by solvent extraction process. Parameters affecting the release kinetics in vitro have been studied in order to design specific release profiles suitable for direct intra-tumoral injection. By varying the nature and the relative proportions of different polymers we managed to prepare microspheres with good encapsulation efficiency (75-90%) and four different release profiles: zero order kinetics (type II) and the classical sigmoïd release profile with three different sizes of plateau and burst. These results, if correlated with in vivo activity, are promising to enhance effectiveness of local tumor treatment.

Drug Release Kinetics and Front Movement in Matrix Tablets Containing Diltiazem or Metoprolol/λ-Carrageenan Complexes

PubMed Central

Bonferoni, Maria Cristina; Colombo, Paolo; Zanelotti, Laura; Caramella, Carla

2014-01-01

In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer. PMID:25045689

Drug release kinetics and front movement in matrix tablets containing diltiazem or metoprolol/λ-carrageenan complexes.

PubMed

Bettini, Ruggero; Bonferoni, Maria Cristina; Colombo, Paolo; Zanelotti, Laura; Caramella, Carla

2014-01-01

In this work we investigated the moving boundaries and the associated drug release kinetics in matrix tablets prepared with two complexes between λ-carrageenan and two soluble model drugs, namely, diltiazem HCl and metoprolol tartrate aiming at clarifying the role played by drug/polymer interaction on the water uptake, swelling, drug dissolution, and drug release performance of the matrix. The two studied complexes released the drug with different mechanism indicating two different drug/polymer interaction strengths. The comparison between the drug release behaviour of the complexes and the relevant physical mixtures indicates that diltiazem gave rise to a less soluble and more stable complex with carrageenan than metoprolol. The less stable metoprolol complex afforded an erodible matrix, whereas the stronger interaction between diltiazem and carrageenan resulted in a poorly soluble, slowly dissolving matrix. It was concluded that the different stability of the studied complexes affords two distinct drug delivery systems: in the case of MTP, the dissociation of the complex, as a consequence of the interaction with water, affords a classical soluble matrix type delivery system; in the case of DTZ, the dissolving/diffusing species is the complex itself because of the very strong interaction between the drug and the polymer.

Influence of lactose addition to gentamicin-loaded acrylic bone cement on the kinetics of release of the antibiotic and the cement properties.

PubMed

Frutos, Gloria; Pastor, José Ygnacio; Martínez, Noelia; Virto, María Rosa; Torrado, Susana

2010-03-01

The purpose of this study was to characterize a poly(methyl methacrylate) bone cement that was loaded with the antibiotic gentamicin sulphate (GS) and lactose, which served to modulate the release of GS from cement specimens. The release of GS when the cement specimens were immersed in phosphate-buffered saline at 37 degrees Celsius was determined spectrophotometrically. The microstructure, porosity, density, tensile properties and flexural properties of the cements were determined before and after release of GS. A kinetics model of the release of GS from the cement that involved a coupled mechanism based on dissolution/diffusion processes and an initial burst effect was proposed. Dissolution assay results showed that drug elution was controlled by a diffusion mechanism which can be modulated by lactose addition. Density values and mechanical properties (tensile strength, flexural strength, elastic modulus and fracture toughness) were reduced by the increased porosity resulting from lactose addition, but maintained acceptable values for the structural functions of bone cement. The present results suggest that lactose-modified, gentamicin-loaded acrylic bone cements are potential candidates for use in various orthopaedic and dental applications. Copyright 2009 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

pH-controlled drug release for dental applications

NASA Astrophysics Data System (ADS)

Wironen, John Francis

A large proportion of the dental fillings replaced at present are revised because of the perceived presence of a recurrent caries under or adjacent to the restoration. Many of these perceived caries may not exist, while others may go undetected. This work describes the preparation of drug loaded polymer microspheres that sense the presence of the bacteria that cause caries by the associated presence of acid by-products of digestion. These microspheres are designed to swell and release their antimicrobial drugs once the pH drops to a level that would normally cause caries. The preparation of the microspheres as well as their loading with potassium fluoride, chlorhexidine digluconate, chlorhexidine dihydrochloride, chlorhexidine diacetate, and tetracycline hydrochloride are described. A detailed study of the controlled release behavior of fluoride as a function of polymer composition and pH is presented first. A study of the release kinetics of potassium fluoride, chlorhexidine digluconate, diacetate, dihydrochloride, and tetracycline hydrochloride as a function of pH in the same polymer system is then presented. Additional studies of the swelling kinetics of chlorhexidine-loaded microspheres in various pH buffers are discussed with special reference to correlations with the controlled-release data. Finally, an experiment in which the microspheres are tested in an in vitro bacteria model that includes Streptococcus mutans is presented and discussed in detail.

Kinetic analysis of the interactions between calcium ferrite and coal char for chemical looping gasification applications: Identifying reduction routes and modes of oxygen transfer

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

Riley, Jarrett; Siriwardane, Ranjani; Tian, Hanjing

Chemical Looping Gasification (CLG) is an emerging technology that shows promise for efficient coal gasification by eliminating the need for energy intensive gas separations to achieve a non-nitrogen diluted syngas stream. Oxygen from oxygen carriers, such as CaFe 2O 4, are used for coal gasification in place of conventionally produced gaseous oxygen from cryogenic separation of air. These oxygen carriers are unique for their ability to selectively oxidize coal to form syngas and show limited reactivity with syngas components (H 2, CO). To gain a deeper understanding of how these unique oxygen carriers perform and to offer a first attemptmore » at the reaction modeling of solid mediated interactions of this nature, this study was carried out to determine the kinetic parameters associated with the selective oxidation of coal derived char (Wyodak and Illinois #6) with a metal ferrite, CaFe 2O 4. Using thermogravimetric analysis (TGA) coupled with mass spectrometry, the selective oxygen release of metal ferrite in the presence of char by proximal contact was examined. The application of combinatory model fitting approaches was used to describe controlling resistances during oxygen release. A combination of the modified shrinking core model (SCM) with planar oxygen ion diffusion control and reaction order based models was used for kinetic parameter determination. CaFe 2O 4 particle size plays a major role in the prevailing mode of oxygen release. Particle sizes on the order of 40–50 μm tend to favor first order kinetically controlled regimes independent of geometric and diffusion controls. The probability for oxygen ion diffusion controlling regimes increased when the particle size range of the oxygen carrier was increased up to 350 μm. Char type also impacted the prevalence of the controlling regime. Higher ranked chars react in a slower manner, limiting the gradient for oxygen ion release from the oxygen carrier. Activation energies determined for this process range from 120–200kJ/mol and oxygen ion diffusion coefficients are on the order of 10-8 cm 2/s. It is suggested that oxygen ion movement is regulated by lattice diffusion out of partially reduced phases (Ca 2Fe 2O 5) and through reduced outer layers composed of CaO and Fe. The controlled movement of oxygen ions influences the rate of carbon oxidation in the char and therefore the selectivity towards partial oxidation products, which are desirable in CLG applications.« less

Kinetic analysis of the interactions between calcium ferrite and coal char for chemical looping gasification applications: Identifying reduction routes and modes of oxygen transfer

DOE PAGES

Riley, Jarrett; Siriwardane, Ranjani; Tian, Hanjing; ...

2017-05-20

Chemical Looping Gasification (CLG) is an emerging technology that shows promise for efficient coal gasification by eliminating the need for energy intensive gas separations to achieve a non-nitrogen diluted syngas stream. Oxygen from oxygen carriers, such as CaFe 2O 4, are used for coal gasification in place of conventionally produced gaseous oxygen from cryogenic separation of air. These oxygen carriers are unique for their ability to selectively oxidize coal to form syngas and show limited reactivity with syngas components (H 2, CO). To gain a deeper understanding of how these unique oxygen carriers perform and to offer a first attemptmore » at the reaction modeling of solid mediated interactions of this nature, this study was carried out to determine the kinetic parameters associated with the selective oxidation of coal derived char (Wyodak and Illinois #6) with a metal ferrite, CaFe 2O 4. Using thermogravimetric analysis (TGA) coupled with mass spectrometry, the selective oxygen release of metal ferrite in the presence of char by proximal contact was examined. The application of combinatory model fitting approaches was used to describe controlling resistances during oxygen release. A combination of the modified shrinking core model (SCM) with planar oxygen ion diffusion control and reaction order based models was used for kinetic parameter determination. CaFe 2O 4 particle size plays a major role in the prevailing mode of oxygen release. Particle sizes on the order of 40–50 μm tend to favor first order kinetically controlled regimes independent of geometric and diffusion controls. The probability for oxygen ion diffusion controlling regimes increased when the particle size range of the oxygen carrier was increased up to 350 μm. Char type also impacted the prevalence of the controlling regime. Higher ranked chars react in a slower manner, limiting the gradient for oxygen ion release from the oxygen carrier. Activation energies determined for this process range from 120–200kJ/mol and oxygen ion diffusion coefficients are on the order of 10-8 cm 2/s. It is suggested that oxygen ion movement is regulated by lattice diffusion out of partially reduced phases (Ca 2Fe 2O 5) and through reduced outer layers composed of CaO and Fe. The controlled movement of oxygen ions influences the rate of carbon oxidation in the char and therefore the selectivity towards partial oxidation products, which are desirable in CLG applications.« less

Kinetics of silver release from microfuel with taking into account the limited-solubility effect

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

Ivanov, A. S., E-mail: asi.kiae@gmail.com; Rusinkevich, A. A., E-mail: rusinkevich_andr@mail.ru

2014-12-15

The effect of a limited solubility of silver in silicon carbide on silver release from a microfuel with a TRISO coating is studied. It is shown that a limited solubility affects substantially both concentration profiles and silver release from a microfuel over a broad range of temperatures. A procedure is developed for obtaining fission-product concentration profiles in a microfuel and graphs representing the flow and integrated release of fission products on the basis of data from neutron-physics calculations and results obtained by calculating thermodynamics with the aid of the Ivtanthermo code and kinetics with the aid of the FP-Kinetics code.more » This procedure takes into account a limited solubility of fission products in protective coatings of microfuel.« less

Real-time monitoring of anticancer drug release with highly fluorescent star-conjugated copolymer as a drug carrier.

PubMed

Qiu, Feng; Wang, Dali; Zhu, Qi; Zhu, Lijuan; Tong, Gangsheng; Lu, Yunfeng; Yan, Deyue; Zhu, Xinyuan

2014-04-14

Chemotherapy is one of the major systemic treatments for cancer, in which the drug release kinetics is a key factor for drug delivery. In the present work, a versatile fluorescence-based real-time monitoring system for intracellular drug release has been developed. First, two kinds of star-conjugated copolymers with different connections (e.g., pH-responsive acylhydrazone and stable ether) between a hyperbranched conjugated polymer (HCP) core and many linear poly(ethylene glycol) (PEG) arms were synthesized. Owing to the amphiphilic three-dimensional architecture, the star-conjugated copolymers could self-assemble into multimicelle aggregates from unimolecular micelles with excellent emission performance in the aqueous medium. When doxorubicin (DOX) as a model drug was encapsulated into copolymer micelles, the emission of star-conjugated copolymer and DOX was quenched. In vitro biological studies revealed that fluorescent intensities of both star-conjugated copolymer and DOX were activated when the drug was released from copolymeric micelles, resulting in the enhanced cellular proliferation inhibition against cancer cells. Importantly, pH-responsive feature of the star-conjugated copolymer with acylhydrazone linkage exhibited accelerated DOX release at a mildly acidic environment, because of the fast breakage of acylhydrazone in endosome or lysosome of tumor cells. Such fluorescent star-conjugated copolymers may open up new perspectives to real-time study of drug release kinetics of polymeric drug delivery systems for cancer therapy.

Drug loading optimization and extended drug delivery of corticoids from pHEMA based soft contact lenses hydrogels via chemical and microstructural modifications.

PubMed

García-Millán, Eva; Koprivnik, Sandra; Otero-Espinar, Francisco Javier

2015-06-20

This paper proposes an approach to improve drug loading capacity and release properties of poly(2-hydroxyethyl methacrylate) (p(HEMA)) soft contact lenses based on the optimization of the hydrogel composition and microstructural modifications using water during the polymerization process. P(HEMA) based soft contact lenses were prepared by thermal or photopolymerization of 2-hydroxyethyl methacrylate (HEMA) solutions containing ethylene glycol di-methacrylate as crosslinker and different proportions of N-vinyl-2-pyrrolidone (NVP) or methacrylic acid (MA) as co-monomers. Transmittance, water uptake, swelling, microstructure, drug absorption isotherms and in vitro release were characterized using triamcinolone acetonide (TA) as model drug. Best drug loading ratios were obtained with lenses containing the highest amount (200 mM) of MA. Incorporation of 40% V/V of water during the polymerization increases the hydrogel porosity giving a better drug loading capacity. In vitro TA release kinetics shows that MA hydrogels released the drug significantly faster than NVP-hydrogels. Drug release was found to be diffusion controlled and kinetics was shown to be reproducible after consecutive drug loading/release processes. Results of p(HEMA) based soft contact lenses copolymerized with ethylene glycol dimethacrylate (EGDMA) and different co-monomers could be a good alternative to optimize the loading and ocular drug delivery of this corticosteroid drug. Copyright © 2015. Published by Elsevier B.V.

Relationships between solid dispersion preparation process, particle size and drug release--an NMR and NMR microimaging study.

PubMed

Dahlberg, Carina; Millqvist-Fureby, Anna; Schuleit, Michael; Furó, István

2010-10-01

Solid dispersion tablets prepared by either spray drying or rotoevaporation and exhibiting different grain and pore sizes were investigated under the process of hydration-swelling-gelation. (2)H and (1)H NMR microimaging experiments were used to selectively follow water penetration and polymer mobilization kinetics, respectively, while the drug release kinetics was followed by (1)H NMR spectroscopy. The obtained data, in combination with morphological information by scanning electron microscopy (SEM), reveal a complex process that ultimately leads to release of the drug into the aqueous phase. We find that the rate of water ingress has no direct influence on release kinetics, which also renders air in the tablets a secondary factor. On the other hand, drug release is directly correlated with the polymer mobilization kinetics. Water diffusion into the originally dry polymer grains determines the rate of grain swelling and the hydration within the grains varies strongly with grain size. We propose that this sets the stage for creating homogeneous gels for small grain sizes and heterogeneous gels for large grain sizes. Fast diffusion through water-rich sections of the inhomogeneous gels that exhibit a large mesh size is the factor which yields a faster drug release from tablets prepared by rotoevaporation. Copyright © 2010. Published by Elsevier B.V.

Fluoride release and recharge behavior of a nano-filled resin-modified glass ionomer compared with that of other fluoride releasing materials.

PubMed

Mitra, Sumita B; Oxman, Joe D; Falsafi, Afshin; Ton, Tiffany T

2011-12-01

To compare the long-term fluoride release kinetics of a novel nano-filled two-paste resin-modified glass-ionomer (RMGI), Ketac Nano (KN) with that of two powder-liquid resin-modified glass-ionomers, Fuji II LC (FLC) and Vitremer (VT) and one conventional glass-ionomer, Fuji IX (FIX). Fluoride release was measured in vitro using ion-selective electrodes. Kinetic analysis was done using regression analysis and compared with existing models for GIs and compomers. In a separate experiment the samples of KN and two conventional glass-ionomers, FIX and Ketac Molar (KM) were subjected to a treatment with external fluoride source (Oral-B Neutra-Foam) after 3 months of fluoride release and the recharge behavior studied for an additional 7-day period. The cumulative amount of fluoride released from KN, VT and FLC and the release profiles were statistically similar but greater than that for FIX at P < 0.05. All four materials, including KN, showed a burst of fluoride ions at shorter times (t) and an overall rate dependence on t1/2 typical for glass-ionomers. The coating of KN with its primer and of DY with its adhesive did not significantly alter the fluoride release behavior of the respective materials. The overall rate for KN was significantly higher than for the compomer DY. DY showed a linear rate of release vs. t and no burst effect as expected for compomers. The nanoionomer KN showed fluoride recharge behavior similar to the conventional glass ionomers FIX and KM. Thus, it was concluded that the new RMGI KN exhibits fluoride ion release behavior similar to typical conventional and RMGIs and that the primer does not impede the release of fluoride.

[Effects of several low-molecular-weight organic acids on the release kinetic of endosulfan from red soil].

PubMed

Zhao, Zhen-hua; Wu, Yu; Jiang, Xin; Xia, Li-ling; Ni, Li-xiao

2009-10-15

The kinetic release behaviors of a-endosulfan from red soil with three kinds of low-molecular-weight organic acids (LMWOA: oxalate, tartrate and citrate) solution and water leaching were investigated by kinetic device designed by ourselves and batch method. The results show that: the release percentage of endosulfan from red soil by tartrate and citrate solution (10 mmol/L) can increase by 7%-18% more than that by distilled water and oxalate solution, especially for tartrate solution. There is no significant difference between distilled water and oxalate solution for the release percentage of endosulfan (p > 0.05). There are two stages of quick and slow for the release of endosulfan from red soil, and the leaching speed is quicker especially for the initial 200 mL leaching solution. When using distilled water or oxalate solution as leaching solution, the best equations that described the kinetic release behavior of endosulfan from red soil were parabola diffuse equation and double constant equation, and weren't the apparent first dynamics equation that represented the simple surface diffusion mechanism. The kinetic release behavior of endosulfan in tartrate or citrate leaching system can be described by Elovich equation (R2 > 0.99, p < 0.0001), it implied that the simple surface diffusion mechanism is not the primary factor that effected the release of endosulfan, which three-dimensional molecule structure is complex, from red soil in aqueous phase leaching systems, and it maybe related to the outward diffuse mechanism from soil particle, activation and deactivation function of soil particles surface, the dissolution of soil mineral surface and structure change of inherent organic matter that coating onto the soil mineral surface induced by LMW organic acid. It suggested that the tartrate and citrate induced the complication of the release mechanisms of the pesticides from red soil.

Combustion Of Metals In Reduced Gravity And Extraterrestrial Environments

NASA Technical Reports Server (NTRS)

Abbud-Madrid, A.; Modak, A.; Branch, M. C.

2003-01-01

The recent focus of this research project has been to model the combustion of isolated metal droplets and, in particular, to couple the existing theories and formulations of phenomena such as condensation, reaction kinetics, radiation, and surface reactions to formulate a more complete combustion model. A fully transient, one-dimensional (spherical symmetry) numerical model that uses detailed chemical kinetics, multi-component molecular transport mechanisms, condensation kinetics, and gas phase radiation heat transfer was developed. A coagulation model was used to simulate the particulate formation of MgO. The model was used to simulate the combustion of an Mg droplet in pure O2 and CO2. Methanol droplet combustion is considered as a test case for the solution method for both quasi-steady and fully transient simulations. Although some important processes unique to methanol combustion, such as water absorption at the surface, are not included in the model, the results are in sufficient agreement with the published data. Since the major part of the heat released in combustion of Mg, and in combustion of metals in general, is due to the condensation of the metal oxide, it is very important to capture the condensation processes correctly. Using the modified nucleation theory, an Arrhenius type rate expression is derived to calculate the condensation rate of MgO. This expression can be easily included in the CHEMKIN reaction mechanism format. Although very little property data is available for MgO, the condensation rate expression derived using the existing data is able to capture the condensation of MgO. An appropriate choice of the reference temperature to calculate the rate coefficients allows the model to correctly predict the subsequent heat release and hence the flame temperature.

Physicochemical properties affect the synthesis, controlled delivery, degradation and pharmacokinetics of inorganic nanoporous materials.

PubMed

Yazdi, Iman K; Ziemys, Arturas; Evangelopoulos, Michael; Martinez, Jonathan O; Kojic, Milos; Tasciotti, Ennio

2015-10-01

Controlling size, shape and uniformity of porous constructs remains a major focus of the development of porous materials. Over the past two decades, we have seen significant developments in the fabrication of new, porous-ordered structures using a wide range of materials, resulting in properties well beyond their traditional use. Porous materials have been considered appealing, due to attractive properties such as pore size length, morphology and surface chemistry. Furthermore, their utilization within the life sciences and medicine has resulted in significant developments in pharmaceutics and medical diagnosis. This article focuses on various classes of porous materials, providing an overview of principle concepts with regard to design and fabrication, surface chemistry and loading and release kinetics. Furthermore, predictions from a multiscale mathematical model revealed the role pore length and diameter could have on payload release kinetics.

Bioaccessibility of polyphenols associated with dietary fiber and in vitro kinetics release of polyphenols in Mexican 'Ataulfo' mango (Mangifera indica L.) by-products.

PubMed

Blancas-Benitez, Francisco J; Mercado-Mercado, Gilberto; Quirós-Sauceda, Ana E; Montalvo-González, Efigenia; González-Aguilar, Gustavo A; Sáyago-Ayerdi, Sonia G

2015-03-01

The biological properties of polyphenol (PP) depend on its bioaccessibility and bioavailability. Therefore, part of PP released from the food matrix in the gastrointestinal tract through enzymatic hydrolysis is at least partially absorbed. The aim of this study is to determine the bioaccessibility of PP associated with dietary fiber (DF) and the kinetics release of PP in mango (Mangifera indica L.) 'Ataulfo' by-products by an in vitro model. Soluble and insoluble DF values were 7.99 and 18.56% in the mango paste and 6.98 and 22.78% in the mango peel, respectively. PP associated with soluble and insoluble DF was 6.0 and 3.73 g GAE per 100 g in the paste and 4.72 and 4.50 g GAE per 100 g in the peel. The bioaccessibility of PP was 38.67% in the pulp paste and 40.53% in the peel. A kinetics study shows a release rate of 2.66 and 3.27 g PP min(-1) in the paste and peel, respectively. The antioxidant capacity of the paste increased as digestion reached a value of 2.87 mmol TE min(-1) at 180 min. The antioxidant capacity of the peel had its maximum (28.94 mmol TE min(-1)) between 90 and 120 min of digestion; it started with a value of 2.58 mmol TE min(-1), and thereafter increased to 4.20 mmol TE min(-1) at 180 min. The major PPs released during the digestion of paste were gallic and hydroxybenzoic acids, while in the peel, they were hydroxycinnamic and vanillic acids. It was concluded that these phenolic compounds are readily available for absorption in the small intestine and exert different potential health benefits.

Empirical and mechanistic evaluation of NH4(+) release kinetic in calcareous soils.

PubMed

Ranjbar, F; Jalali, M

2014-05-01

Release, fixation, and distribution of ammonium (NH4(+)) as a source of nitrogen can play an important role in soil fertility and plant nutrition. In this study, ten surface soils, after addition of 1,000 mg NH4(+) kg(-1,) were incubated for 1 week at the field capacity moisture and 25 ± 2 °C temperature, and then NH4(+) release kinetic was investigated by sequential extractions with 10 mM CaCl2. Furthermore, NH4(+) distribution among three fractions, including water-soluble, exchangeable, and non-exchangeable, was determined in all soil samples. NH4(+) release was initially rapid followed by a slower reaction, and this was described well with the Elovich equation as an empirical model. The cumulative NH4(+) concentration released in spiked soil samples had a positive significant correlation with sand content and negative ones with pH, exchangeable Ca(2+)m and K(+), cation exchange capacity (CEC), equivalent calcium carbonate (ECC), and clay content. The cation exchange model in the PHREEQC program was successful in mechanistic simulation of the release trend of native and added NH4(+) in all control and spiked soil samples. The results of fractionation experiments showed that the non-exchangeable fraction in control and spiked soil samples was greater than that in water-soluble and exchangeable fractions. Soil properties, such as pH, exchangeable Ca(2+) and K(+), CEC, ECC, and contents of sand and clay, had significant influences on the distribution of NH4(+) among three measured fractions. This study indicated that both native and recently fixed NH4(+), added to soil through the application of fertilizers, were readily available for plant roots during 1 week after exposure.

Differential Signalling and Kinetics of Neutrophil Extracellular Trap Release Revealed by Quantitative Live Imaging.

PubMed

van der Linden, Maarten; Westerlaken, Geertje H A; van der Vlist, Michiel; van Montfrans, Joris; Meyaard, Linde

2017-07-26

A wide variety of microbial and inflammatory factors induce DNA release from neutrophils as neutrophil extracellular traps (NETs). Consensus on the kinetics and mechanism of NET release has been hindered by the lack of distinctive methods to specifically quantify NET release in time. Here, we validate and refine a semi-automatic live imaging approach for quantification of NET release. Importantly, our approach is able to correct for neutrophil input and distinguishes NET release from neutrophil death by other means, aspects that are lacking in many NET quantification methods. Real time visualization shows that opsonized S. aureus rapidly induces cell death by toxins, while actual NET formation occurs after 90 minutes, similar to the kinetics of NET release by immune complexes and PMA. Inhibition of SYK, PI3K and mTORC2 attenuates NET release upon challenge with physiological stimuli but not with PMA. In contrast, neutrophils from chronic granulomatous disease patients show decreased NET release only in response to PMA. With this refined method, we conclude that NET release in primary human neutrophils is dependent on the SYK-PI3K-mTORC2 pathway and that PMA stimulation should be regarded as mechanistically distinct from NET formation induced by natural triggers.

[Entrapment of herbal extracts in biodegradable microcapsules].

PubMed

Borodina, T N; Rumsh, L D; Kunizhev, S M; Sukhorukov, G B; Vorozhtsov, G N; Fel'dman, B M; Rusanova, A V; Vasil'eva, T V; Strukova, S M; Markvicheva, E A

2007-01-01

The microcapsules with entrapped herbal water-soluble extracts Plantago major and Calendula officinalis L. (HE) were prepared by LbL-adsorption of carrageenan and modificated chitosan onto CaCO3 microparticles with their subsequent dissolving after the treatment of EDTA. Entrapment of HE was performed by adsorption and co-precipitation techniques. The co-precipitation provided better entrapment of HE compared to adsorption. In vitro release kinetics in an artificial gastric juice (AGJ) was studied. The HE release was shown to accelerate gastric ulcer treatment in a rat model.

Albumin nanoparticles coated with polysorbate 80 as a novel drug carrier for the delivery of antiretroviral drug—Efavirenz

PubMed Central

Jenita, Josephine Leno; Chocalingam, Vijaya; Wilson, Barnabas

2014-01-01

Purpose of the study: The antiretroviral therapy (ART) has dramatically improved human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) treatment, prevention and also has been found to increase the lifespan of HIV/AIDS patients by providing durable control of the HIV replication in patients. Efavirenz is a non-nucleoside reverse transcriptase inhibitor of HIV-1. The purpose of this study is to formulate efavirenz-loaded bovine serum albumin nanoparticles to improve efavirenz delivery into various organs. Materials and Methods: Nanoparticles were prepared by desolvation technique and coated with polysorbate 80. Ethanol, glutaraldehyde, and mannitol were used as desolvating, cross linking agent, and cryoprotectant, respectively. Drug to polymer ratio was chosen at five levels from 1:2, 1:3, 1:4, 1:5, and 1:6 (by weight). The formulated nanoparticles were characterized for Fourier Transform Infrared (FT-IR) spectroscopy, differential scanning calorimetry (DSC) studies, entrapment efficiency, particle size, surface charge, surface morphology, in vitro drug release, release kinetics, stability studies, and biodistribution studies. Results and Major Conclusion: The particle size of the prepared formulations was found below 250nm with narrow size distribution, spherical in shape and showed good entrapment efficiency (45.62-72.49%). The in vitro drug release indicated biphasic release and its data were fitted to release kinetics models and release pattern was Fickian diffusion controlled release profile. The prepared nanoparticles increased efavirenz delivery into various organs by several fold in comparison with the free drug. PMID:25126528

A Pre-Steady State Kinetic Analysis of the αY60W mutant of trans-3-Chloroacrylic Acid Dehalogenase: Implications for the Mechanism of the Wild-type Enzyme†

PubMed Central

Huddleston, Jamison P.; Schroeder, Gottfried K.; Johnson, Kenneth A.; Whitman, Christian P.

2012-01-01

The bacterial degradation of the nematicide 1,3-dichloropropene, an isomeric mixture, requires the action of trans- and cis-3-chloracrylic acid dehalogenase (CaaD and cis-CaaD, respectively). Both enzymes are tautomerase superfamily members and share a core catalytic mechanism for the hydrolytic dehalogenation of the respective isomer of 3-haloacrylate. The observation that cis-CaaD requires two additional residues raises the question of how CaaD carries out a comparable reaction with fewer catalytic residues. As part of an effort to determine the basis for the apparently simpler CaaD-catalyzed reaction, the kinetic mechanism was determined by stopped-flow and chemical quench techniques using a fluorescent mutant form of the enzyme, αY60W-CaaD, and trans-3-bromoacrylate as the substrate. The data from these experiments as well as bromide inhibition studies are best accommodated by a six-step model that provides individual rate constants for substrate binding, chemistry, and a proposed conformational change occurring after chemistry followed by release of malonate semialdehyde and bromide. The conformational change and product release rates are comparable and together they limit the rate of turnover. The kinetic analysis and modeling studies validate the αY60W-CaaD mutant as an accurate reporter of active site events during the course of the enzyme-catalyzed reaction. The kinetic mechanism for the αY60W-CaaD-catalyzed reaction is comparable to that obtained for the cis-CaaD-catalyzed reaction. The kinetic model and the validated αY60W-CaaD mutant set the stage for an analysis of active site mutants to explore the contributions of individual catalytic residues and the basis for the simplicity of the reaction. PMID:23110338

Controlled release of tetracycline-HCl from halloysite-polymer composite films.

PubMed

Ward, Christopher J; Song, Shang; Davis, Edward W

2010-10-01

The first direct comparison between two common methods for loading halloysite with a small molecule for controlled release is presented. While the methods differ in the degree of simplicity, they provide essentially the same level of loading and release kinetics. A tentative explanation of the "burst" effect often seen in the release of low molecular weight molecules from halloysite is provided. The ability of halloysite to mediate the release rate of a water soluble drug, tetracycline, from solution cast polyvinyl alcohol and polymethyl methacrylate films was evaluated. In some films, montmorillonite was also incorporated. The addition of montmorillonite to solutions used to cast tetracycline containing films significantly reduced the release rate from the dried films. The same overall effect was seen when the drug was loaded into halloysite prior to preparation of the films. In both cases, the release was best fit with the simple Higuchi model. However, when montmorillonite was added to solutions of polyvinyl alcohol and drug loaded halloysite the release profiles were better fit by the Ritgar-Peppas model for anomalous transport. Release from polymethyl methacrylate was reduced by a factor of three by incorporating the drug in halloysite prior to producing the films.

Adding kinetics and hydrodynamics to the CHEETAH thermochemical code

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

Fried, L.E., Howard, W.M., Souers, P.C.

1997-01-15

In FY96 we released CHEETAH 1.40, which made extensive improvements on the stability and user friendliness of the code. CHEETAH now has over 175 users in government, academia, and industry. Efforts have also been focused on adding new advanced features to CHEETAH 2.0, which is scheduled for release in FY97. We have added a new chemical kinetics capability to CHEETAH. In the past, CHEETAH assumed complete thermodynamic equilibrium and independence of time. The addition of a chemical kinetic framework will allow for modeling of time-dependent phenomena, such as partial combustion and detonation in composite explosives with large reaction zones. Wemore » have implemented a Wood-Kirkwood detonation framework in CHEETAH, which allows for the treatment of nonideal detonations and explosive failure. A second major effort in the project this year has been linking CHEETAH to hydrodynamic codes to yield an improved HE product equation of state. We have linked CHEETAH to 1- and 2-D hydrodynamic codes, and have compared the code to experimental data. 15 refs., 13 figs., 1 tab.« less

Bioactive Nano-Fibrous Scaffolds for Bone and Cartilage Tissue Engineering

NASA Astrophysics Data System (ADS)

Feng, Kai

Scaffolds that can mimic the structural features of natural extracellular matrix and can deliver biomolecules in a controlled fashion may provide cells with a favorable microenvironment to facilitate tissue regeneration. Biodegradable nanofibrous scaffolds with interconnected pore network have previously been developed in our laboratory to mimic collagen matrix and advantageously support both bone and cartilage regeneration. This dissertation project aims to expand both the structural complexity and the biomolecule delivery capacity of such biomimetic scaffolds for tissue engineering. We first developed a nanofibrous scaffold that can release an antibiotic (doxycycline) with a tunable release rate and a tunable dosage, which was demonstrated to be able to inhibit bacterial growth over a prolonged time period. We then developed a nanofibrous tissue-engineciing scaffold that can release basic fibroblast growth factor (bFGF) in a spatially and temporally controlled fashion. In a mouse subcutaneous implantation model, the bFGF-releasing scaffold was shown to enhance cell penetration, tissue ingrowth and angiogenesis. It was also found that both the dose and the release rate of bFGF play roles in the biologic function of the scaffold. After that, we developed a nanofibrous PLLA scaffold that can release both bone morphogenetic protein 7 (BMP-7) and platelet-derived growth factor (PDGF) with distinct dosages and release kinetics. It was demonstrated that BMP-7 and PDGF could synergistically enhance bone regeneration using a mouse ectopic bone formation model and a rat periodontal fenestration defect regeneration model. The regeneration outcome was dependent on the dosage, the ratio and the release kinetics of the two growth factors. Last, we developed an anisotropic composite scaffold with an upper layer mimicking the superficial zone of cartilage and a lower layer mimicking the middle zone of cartilage. The thin superficial layer was fabricated using an electrospinning technique to support a more parallel ECM orientation to the cartilage surface. The lower layer was fabricated using a phase-separation technique to support a more isotropic ECM distribution. Human bone marrow-derived mesenchymal stem cells (hMSCs) were seeded on this complex scaffold and cultured under chondrogenic conditions. The results showed that the composite scaffold was indeed able to support anisotropic cartilage tissue structure formation.

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

PubMed

Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

2010-01-01

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

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.

In vitro kinetic investigations on the bioactivity and cytocompatibility of bioactive glasses prepared via melting and sol-gel techniques for bone regeneration applications.

PubMed

El-Sayed, Mayyada M H; Mostafa, Amany A; Gaafar, Alaa M; El Hotaby, Walid; Hamzawy, Esmat Ma; El-Okaily, Mohamed S; Gamal-Eldeen, Amira M

2017-02-24

This work investigates and compares the influence of the synthesis process on the in vitro bioactivity of two quaternary bioactive glasses prepared via melting and sol-gel (SG) techniques. The two glasses are named MG and SG, respectively. Powder samples were soaked in simulated body fluid for different time intervals to study the kinetics of Ca and P uptake onto their surface as well as Si release. The uptake kinetics followed the pseudo-second order model, and the kinetic parameters in addition to the initial rates were estimated. MG manifested higher Ca uptake capacity than SG which could be attributed to the presence of a residual organic layer capping the surface of SG, as was confirmed by Fourier transform infrared and nuclear magnetic resonance analyses. However, higher rate of Ca uptake was exhibited by SG probably due to its higher reactivity that resulted from its smaller nano-size and higher negative charge as was evident from transmission electron microscopy and dynamic light scattering measurements, respectively. Furthermore, MG showed slightly higher P uptake capacity and lower amount of Si release. Initial rates of Ca and P uptakes onto SG as well as Si release from SG exceeded those of MG. Human bone osteosarcoma cells (Saos-2) were co-cultured with both MG and SG glasses and the latter showed higher alkaline phosphatase activity and higher cell growth induction. The results showed the promising potential of using both bioactive glasses in bone regeneration. However, the choice of the appropriate bioactive glass depends on the targeted applications.

Effect of mean diameter and polydispersity of PLG microspheres on drug release: experiment and theory.

PubMed

Berchane, N S; Carson, K H; Rice-Ficht, A C; Andrews, M J

2007-06-07

The need to tailor release rate profiles from polymeric microspheres is a significant problem. Microsphere size, which has a significant effect on drug release rate, can potentially be varied to design a controlled drug delivery system with desired release profile. In this work the effects of microspheres mean diameter, polydispersity, and polymer degradation on drug release rate from poly(lactide-co-glycolide) (PLG) microspheres are described. Piroxicam containing PLG microspheres were fabricated at 20% loading, and at three different impeller speeds. A portion of the microspheres was then sieved giving five different size distributions. In vitro release kinetics were determined for each preparation. Based on these experimental results, a suitable mathematical theory has been developed that incorporates the effect of microsphere size distribution and polymer degradation on drug release. We show from in vitro release experiments that microsphere size has a significant effect on drug release rate. The initial release rate decreased with an increase in microsphere size. In addition, the release profile changed from first order to concave-upward (sigmoidal) as the microsphere size was increased. The mathematical model gave a good fit to the experimental release data. For highly polydisperse populations (polydispersity parameter b<3), incorporating the microsphere size distribution into the mathematical model gave a better fit to the experimental results than using the representative mean diameter. The validated mathematical model can be used to predict small-molecule drug release from PLG microsphere populations.

Simple model of inhibition of chain-branching combustion processes

NASA Astrophysics Data System (ADS)

Babushok, Valeri I.; Gubernov, Vladimir V.; Minaev, Sergei S.; Miroshnichenko, Taisia P.

2017-11-01

A simple kinetic model has been suggested to describe the inhibition and extinction of flame propagation in reaction systems with chain-branching reactions typical for hydrocarbon systems. The model is based on the generalised model of the combustion process with chain-branching reaction combined with the one-stage reaction describing the thermal mode of flame propagation with the addition of inhibition reaction steps. Inhibitor addition suppresses the radical overshoot in flame and leads to the change of reaction mode from the chain-branching reaction to a thermal mode of flame propagation. With the increase of inhibitor the transition of chain-branching mode of reaction to the reaction with straight-chains (non-branching chain reaction) is observed. The inhibition part of the model includes a block of three reactions to describe the influence of the inhibitor. The heat losses are incorporated into the model via Newton cooling. The flame extinction is the result of the decreased heat release of inhibited reaction processes and the suppression of radical overshoot with the further decrease of the reaction rate due to the temperature decrease and mixture dilution. A comparison of the results of modelling laminar premixed methane/air flames inhibited by potassium bicarbonate (gas phase model, detailed kinetic model) with the results obtained using the suggested simple model is presented. The calculations with the detailed kinetic model demonstrate the following modes of combustion process: (1) flame propagation with chain-branching reaction (with radical overshoot, inhibitor addition decreases the radical overshoot down to the equilibrium level); (2) saturation of chemical influence of inhibitor, and (3) transition to thermal mode of flame propagation (non-branching chain mode of reaction). The suggested simple kinetic model qualitatively reproduces the modes of flame propagation with the addition of the inhibitor observed using detailed kinetic models.

Release of Ciprofloxacin-HCl and Dexamethasone Phosphate by Hyaluronic Acid Containing Silicone Polymers.

PubMed

Nguyen, Darrene; Hui, Alex; Weeks, Andrea; Heynen, Miriam; Joyce, Elizabeth; Sheardown, Heather; Jones, Lyndon

2012-04-19

The purpose of this study was to determine the effect of the covalent incorporation of hyaluronic acid (HA) into conventional hydrogel and hydrogels containing silicone as models for contact lens materials on the uptake and release of the fluoroquinolone antibiotic ciprofloxacin and the anti-inflammatory steroid dexamethasone phosphate. A 3 mg/mL ciprofloxacin solution (0.3% w/v) and a 1 mg/mL dexamethasone phosphate solution (0.1%) was prepared in borate buffered saline. Three hydrogel material samples (pHEMA; pHEMA TRIS; DMAA TRIS) were prepared with and without the covalent incorporation of HA of molecular weight (MW) 35 or 132 kDa. Hydrogel discs were punched from a sheet of material with a uniform diameter of 5 mm. Uptake kinetics were evaluated at room temperature by soaking the discs for 24 h. Release kinetics were evaluated by placing the drug-loaded discs in saline at 34 °C in a shaking water bath. At various time points over 6-7 days, aliquots of the release medium were assayed for drug amounts. The majority of the materials tested released sufficient drug to be clinically relevant in an ophthalmic application, reaching desired concentrations for antibiotic or anti-inflammatory activity in solution. Overall, the silicone-based hydrogels (pHEMA TRIS and DMAA TRIS), released lower amounts of drug than the conventional pHEMA material (p < 0.001). Materials with HA MW132 released more ciprofloxacin compared to materials with HA MW35 and lenses without HA (p < 0.02). Some HA-based materials were still releasing the drug after 6 days.

Effects of formulation variables and post-compression curing on drug release from a new sustained-release matrix material: polyvinylacetate-povidone.

PubMed

Shao, Z J; Farooqi, M I; Diaz, S; Krishna, A K; Muhammad, N A

2001-01-01

A new commercially available sustained-release matrix material, Kollidon SR, composed of polyvinylacetate and povidone, was evaluated with respect to its ability to modulate the in vitro release of a highly water-soluble model compound, diphenhydramine HCl. Kollidon SR was found to provide a sustained-release effect for the model compound, with certain formulation and processing variables playing an important role in controlling its release kinetics. Formulation variables affecting the release include the level of the polymeric material in the matrix, excipient level, as well as the nature of the excipients (water soluble vs. water insoluble). Increasing the ratio of a water-insoluble excipient, Emcompress, to Kollidon SR enhanced drug release. The incorporation of a water-soluble excipient, lactose, accelerated its release rate in a more pronounced manner. Stability studies conducted at 40 degrees C/75% RH revealed a slow-down in dissolution rate for the drug-Kollidon SR formulation, as a result of polyvinylacetate relaxation. Further studies demonstrated that a post-compression curing step effectively stabilized the release pattern of formulations containing > or = 47% Kollidon SR. The release mechanism of Kollidon-drug and drug-Kollidon-Emcompress formulations appears to be diffusion controlled, while that of the drug-Kollidon-lactose formulation appears to be controlled predominantly by diffusion along with erosion.

Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

PubMed

Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

2002-01-01

The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

Kinetics of mercuric chloride retention by soils

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

Amacher, M.C.; Selim, H.M.; Iskandar, I.K.

A nonlinear multireaction model was used to describe kinetic data for HgCl{sub 2} retention by five soils. A three-parameter version of the model consisting of a reversible nonlinear (nth order, n < 1) reaction and an irreversible first-order reaction was capable of describing HgCl{sub 2} retention data for Cecil (clayey, kaolinitic, thermic Typic Kanhapludult) and Windsor (mixed, mesic Typic Udipsamment) soils at all initial solution Hg concentrations, and data for Norwood, (fine-silty, mixed (calcareous), thermic, Typic Udifluvent), Olivier (fine-silty, mixed, thermic Aquic Fragiudalt), and Sharkey (very-fine, montmorillonitic, nonacid, thermic Vertic Haplaquept) soils at initial solution Hg concentrations below 5 mg/L.more » A five-parameter version of the model, with an added reversible nonlinear reaction, provided a more accurate description of the retention data for the Norwood, Olivier, and Sharkey soils at initial solution Hg concentrations above 5 mg/L. The second reaction needed to describe the data at higher Hg concentrations suggests the presence of a second type of sorption sites, or a precipitation or coprecipitation reaction not encountered at lower Hg concentrations. Release of Hg from the soils was induced by serial dilution of the soil solution, but not all the soil Hg was reversibly retained. This was also indicated by the model. Release of soil Hg depended on the concentration of retained Hg with significant Hg release occurring only at high concentrations of retained Hg. A multireaction model is needed to describe Hg retention in soils because of the many solid phases that can remove Hg from solution.« less

A Hybrid Model for Multiscale Laser Plasma Simulations with Detailed Collisional Physics

DTIC Science & Technology

2017-06-15

Validation against experimental data •Nonequilibrium radiation transport: coupling with a collisional-radiative model •Inelastic collisions in a MF...for Public Release; Distribution is Unlimited. PA# 17383 Collisional Radiative (CR) Overview Updates • Investigated Quasi -Steady-State • Investigated...Techniques Quasi Stead-State (QSS) • Assumes fast kinetics between states within an ion distribution • Assumes longer diffusion/decay times than

Degree of time dependency of kinetic coefficient as a function of adsorbate concentration; new insights from adsorption of tetracycline onto monodispersed starch-stabilized magnetic nanocomposite.

PubMed

Okoli, Chukwunonso P; Ofomaja, Augustine E

2018-07-15

The realization that the observed kinetic coefficient (k obs ) varies with time in most real-time adsorption system, as against the constant value conceived in the most widely-applied adsorption kinetic models, have attracted much attention in recent time. Understanding the factors that control the extent/degree of time dependency (otherwise known as fractal-like kinetics), is therefore central in taking manipulative advantage of this phenomenon in critical adsorption applications. This study therefore deployed non-fractal-like and fractal-like kinetic approach to study the adsorption of tetracycline on monodispersed starch-stabilized magnetite nanocomposite (MSM). MSM was synthesized by in-situ coprecipitation of magnetite in the presence of starch, and successfully characterized with classical solid-state techniques. Isotherm studies indicated that MSM has heterogenous surface adsorption sites. Equilibrium and kinetic data indicated the existence of π-cation interaction as the underlying mechanism, while pH study revealed that tetracycline was adsorbed in its zwitterion form. Though the non-fractal kinetic models exhibited some level of relevance in explaining the tetracycline adsorption interactions, the best fitting of the fractal-like pseudo second order model to the adsorption kinetic data, indicated that the real-time adsorption kinetics occurred in fractal-like manner. The study also revealed that the degree of time dependency of k obs had negative correlation with the initial tetracycline concentration. Apart from developing a low-cost strategy for addressing tetracycline water pollution, the result of this study serves a positive step towards gaining manipulative control of adsorption mechanism in potential application of MSM for targeted drug delivery and controlled release of tetracycline antibiotics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Kinetics of Molybdenum Adsorption and Desorption in Soils.

PubMed

Sun, Wenguang; Selim, H Magdi

2018-05-01

Much uncertainty exists in mechanisms and kinetics controlling the adsorption and desorption of molybdenum (Mo) in the soil environment. To investigate the characteristics of Mo adsorption and desorption and predict Mo behavior in the vadose zone, kinetic batch experiments were performed using three soils: Webster loam, Windsor sand and Mahan sand. Adsorption isotherms for Mo were strongly nonlinear for all three soils. Strong kinetic adsorption of Mo by all soils was also observed, where the rate of retention was rapid initially and was followed by slow retention behavior with time. The time-dependent Mo sorption rate was not influenced when constant pH was maintained. Desorption or release results indicated that there were significant fractions of Mo that appeared to be irreversible or slowly reversibly sorbed by Windsor and Mahan. X-ray absorption near edge structure (XANES) analysis for Windsor and Mahan soils indicated that most of Mo had been bound to kaolinite, whereas Webster had similar XANES features to those of Mo sorbed to montmorillonite. A sequential extraction procedure provided evidence that a significant amount of Mo was irreversibly sorbed. A multireaction model (MRM) with nonlinear equilibrium and kinetic sorption parameters was used to describe the adsorption-desorption kinetics of Mo on soils. Our results demonstrated that a formulation of MRM with two sorption sites (equilibrium and reversible) successfully described Mo adsorption-desorption data for Webster loam, and an additional irreversible reaction phase was recommended to describe Mo desorption or release with time for Windsor and Mahan soils. Copyright © by the American Society of Agronomy, Crop Science Society of America, and Soil Science Society of America, Inc.

ROCKETSHIP: a flexible and modular software tool for the planning, processing and analysis of dynamic MRI studies.

PubMed

Barnes, Samuel R; Ng, Thomas S C; Santa-Maria, Naomi; Montagne, Axel; Zlokovic, Berislav V; Jacobs, Russell E

2015-06-16

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising technique to characterize pathology and evaluate treatment response. However, analysis of DCE-MRI data is complex and benefits from concurrent analysis of multiple kinetic models and parameters. Few software tools are currently available that specifically focuses on DCE-MRI analysis with multiple kinetic models. Here, we developed ROCKETSHIP, an open-source, flexible and modular software for DCE-MRI analysis. ROCKETSHIP incorporates analyses with multiple kinetic models, including data-driven nested model analysis. ROCKETSHIP was implemented using the MATLAB programming language. Robustness of the software to provide reliable fits using multiple kinetic models is demonstrated using simulated data. Simulations also demonstrate the utility of the data-driven nested model analysis. Applicability of ROCKETSHIP for both preclinical and clinical studies is shown using DCE-MRI studies of the human brain and a murine tumor model. A DCE-MRI software suite was implemented and tested using simulations. Its applicability to both preclinical and clinical datasets is shown. ROCKETSHIP was designed to be easily accessible for the beginner, but flexible enough for changes or additions to be made by the advanced user as well. The availability of a flexible analysis tool will aid future studies using DCE-MRI. A public release of ROCKETSHIP is available at https://github.com/petmri/ROCKETSHIP .

An investigation into the characteristics and drug release properties of multiple W/O/W emulsion systems containing low concentration of lipophilic polymeric emulsifier.

PubMed

Vasiljevic, Dragana; Parojcic, Jelena; Primorac, Marija; Vuleta, Gordana

2006-02-17

Multiple W/O/W emulsions with high content of inner phase (Phi1=Phi2=0.8) were prepared using relatively low concentrations of lipophilic polymeric primary emulsifier, PEG 30-dipolyhydroxystearate, and diclofenac diethylamine (DDA) as a model drug. The investigated formulations were characterized and their stability over the time was evaluated by dynamic and oscillatory rheological measurements, microscopic analysis and in vitro drug release study. In vitro release profiles of the selected model drug were evaluated in terms of the effective diffusion coefficients and flux of the released drug. The multiple emulsion samples exhibited good stability during the ageing time. Concentration of the lipophilic primary emulsifier markedly affected rheological behaviour as well as the droplet size and in vitro drug release kinetics of the investigated systems. The multiple emulsion systems with highest concentration (2.4%, w/w) of the primary emulsifier had the lowest droplet size and the highest apparent viscosity and highest elastic characteristics. Drug release data indicated predominately diffusional drug release mechanism with sustained and prolonged drug release accomplished with 2.4% (w/w) of lipophilic emulsifier employed.

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres.

PubMed

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f(1)), the similarity factor (f(2)), and the Rescigno index (ξ(1) and ξ(2)) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations.

Formulation and evaluation of Bacillus coagulans-loaded hypromellose mucoadhesive microspheres

PubMed Central

Alli, Sk Md Athar

2011-01-01

Development of a novel delivery system has been attempted to deliver viable probiotic cells into the gut for a prolonged period of time while maintaining high numbers of viable cells within the formulation throughout the shelf-life of the product and during the gastrointestinal transit. Core mucoadhesive microspheres of Bacillus coagulans were developed employing several grades of hypromellose, a mucoadhesive polymer, following coacervation and phase separation technique and were subsequently enteric-coated with hypromellose phthalate. Microspheres were evaluated for percent yield; entrapment efficiency; in vitro swelling; surface morphology; particle size, size distribution, and zeta potential; flow property, mucoadhesion property by the ex vivo mucoadhesive strength test and the in vitro wash off test; in vitro release profile and release kinetic; in vivo probiotic activity; and stability. The values for the kinetic constant and regression coefficient of model-dependent approaches and the difference factor (f1), the similarity factor (f2), and the Rescigno index (ξ1 and ξ2) of model independent approaches were determined for comparing in vitro dissolution profiles. Freeze dried B. coagulans cells were successfully formulated as enteric-coated mucoadhesive microspheres with satisfactory physical structure and yield. The viability of B. coagulans was maintained in the simulated gastric conditions and during processing; in simulated intestinal conditions exhibiting mucoadhesion, and controlling and extending the viable cell release following zero-order; and was satisfactorily stable at room temperature. Test results depict statistically significant effects of the hypromellose grade and their concentration on the performance and release profile of formulations. PMID:21674019

Design, development and evaluation of clopidogrel bisulfate floating tablets.

PubMed

Rao, K Rama Koteswara; Lakshmi, K Rajya

2014-01-01

The objective of the present work was to formulate and to characterize a floating drug delivery system for clopidogrel bisulphate to improve bioavailability and to minimize the side effects of the drug such as gastric bleeding and drug resistance development. Clopidogrel floating tablets were prepared by direct compression technique by the use of three polymers xanthan gum, hydroxypropyl methylcellulose (HPMC) K15M and HPMC K4M in different concentrations (20%, 25% and 30% w/w). Sodium bicarbonate (15% w/w) and microcrystalline cellulose (30% w/w) were used as gas generating agent and diluent respectively. Studies were carried out on floating behavior and influence of type of polymer on drug release rate. All the formulations were subjected to various quality control and in-vitro dissolution studies in 0.1 N hydrochloric acid (1.2 pH) and corresponding dissolution data were fitted to popular release kinetic equations in order to evaluate release mechanisms and kinetics. All the clopidogrel floating formulations followed first order kinetics, Higuchi drug release kinetics with diffusion as the dominant mechanism of drug release. As per Korsmeyer-Peppas equation, the release exponent "n" ranged 0.452-0.654 indicating that drug release from all the formulations was by non-Fickian diffusion mechanism. The drug release rate of clopidogrel was found to be affected by the type and concentration of the polymer used in the formulation (P < 0.05). As the concentration of the polymer was increased, the drug release was found to be retarded. Based on the results, clopidogrel floating tablets prepared by employing xanthan gum at concentration 25% w/w (formulation F2) was the best formulation with desired in-vitro floating time and drug dissolution.

Effect of surfactant chain length on drug release kinetics from microemulsion-laden contact lenses.

PubMed

Maulvi, Furqan A; Desai, Ankita R; Choksi, Harsh H; Patil, Rahul J; Ranch, Ketan M; Vyas, Bhavin A; Shah, Dinesh O

2017-05-30

The effect of surfactant chain lengths [sodium caprylate (C 8 ), Tween 20 (C 12 ), Tween 80 (C 18 )] and the molecular weight of block copolymers [Pluronic F68 and Pluronic F 127] were studied to determine the stability of the microemulsion and its effect on release kinetics from cyclosporine-loaded microemulsion-laden hydrogel contact lenses in this work. Globule size and dilution tests (transmittance) suggested that the stability of the microemulsion increases with increase in the carbon chain lengths of surfactants and the molecular weight of pluronics. The optical transmittance of direct drug-laden contact lenses [DL-100] was low due to the precipitation of hydrophobic drugs in the lenses, while in microemulsion-laden lenses, the transmittance was improved when stability of the microemulsion was achieved. The results of in vitro release kinetics revealed that drug release was sustained to a greater extent as the stability of microemulsion was improved as well. This was evident in batch PF127-T80, which showed sustained release for 15days in comparison to batch DL-100, which showed release up to 7days. An in vivo drug release study in rabbit tear fluid showed significant increase in mean residence time (MRT) and area under curve (AUC) with PF-127-T80 lenses (stable microemulsion) in comparison to PF-68-SC lenses (unstable microemulsion) and DL-100 lenses. This study revealed the correlation between the stability of microemulsion and the release kinetics of drugs from contact lenses. Thus, it was inferred that the stable microemulsion batches sustained the release of hydrophobic drugs, such as cyclosporine from contact lenses for an extended period of time without altering critical lens properties. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluation of hydrophobic materials as matrices for controlled-release drug delivery.

PubMed

Quadir, Mohiuddin Abdul; Rahman, M Sharifur; Karim, M Ziaul; Akter, Sanjida; Awkat, M Talat Bin; Reza, Md Selim

2003-07-01

The present study was undertaken to evaluate the effect of different insoluble and erodable wax-lipid based materials and their content level on the release profile of drug from matrix systems. Matrix tablets of theophylline were prepared using carnauba wax, bees wax, stearic acid, cetyl alcohol, cetostearyl alcohol and glyceryl monostearate as rate-retarding agents by direct compression process. The release of theophylline from these hydrophobic matrices was studied over 8-hours in buffer media of pH 6.8. Statistically significant difference was found among the drug release profile from different matrices. The release kinetics was found to be governed by the type and content of hydrophobic materials in the matrix. At lower level of wax matrices (25%), a potential burst release was observed with all the materials being studied. Bees wax could not exert any sustaining action while an extensive burst release was found with carnauba wax at this hydrophobic load. Increasing the concentration of fat-wax materials significantly decreased the burst effect of drug from the matrix. At higher hydrophobic level (50% of the matrix), the rate and extent of drug release was significantly reduced due to increased tortuosity and reduced porosity of the matrix. Cetostearyl alcohol imparted the strongest retardation of drug release irrespective of fat-wax level. Numerical fits indicate that the Higuchi square root of time model was the most appropriate one for describing the release profile of theophylline from hydrophobic matrices. The release mechanism was also explored and explained with biexponential equation. Application of this model indicates that Fickian or case I kinetics is the predominant mechanism of drug release from these wax-lipid matrices. The mean dissolution time (MDT) was calculated for all the formulations and the highest MDT value was obtained with cetostearyl matrix. The greater sustaining activity of cetostearyl alcohol can be attributed to some level of swelling and erosion within this matrix at lower fat-wax level which is also supported by release exponent values and Fickian fraction release against time profile of this agent. The results generated in this study showed that proper selection of these hydrophobic materials based on their physico-chemical properties is important in designing wax matrix tablets with desired dissolution profile.

Chitosan nanofibers for transbuccal insulin delivery.

PubMed

Lancina, Michael G; Shankar, Roopa Kanakatti; Yang, Hu

2017-05-01

In this work, they aimed at producing chitosan based nanofiber mats capable of delivering insulin via the buccal mucosa. Chitosan was electrospun into nanofibers using poly(ethylene oxide) (PEO) as a carrier molecule in various feed ratios. The mechanical properties and degradation kinetics of the fibers were measured. Insulin release rates were determined in vitro using an ELISA assay. The bioactivity of released insulin was measured in terms of Akt activation in pre-adipocytes. Insulin permeation across the buccal mucosa was measured in an ex-vivo porcine transbuccal model. Fiber morphology, mechanical properties, and in vitro stability were dependent on PEO feed ratio. Lower PEO content blends produced smaller diameter fibers with significantly faster insulin release kinetics. Insulin showed no reduction in bioactivity due to electrospinning. Buccal permeation of insulin facilitated by high chitosan content blends was significantly higher than that of free insulin. Taken together, the work demonstrates that chitosan-based nanofibers have the potential to serve as a transbuccal insulin delivery vehicle. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1252-1259, 2017. © 2017 Wiley Periodicals, Inc.

Blood modulates the kinetics of reactive oxygen release in pancreatic ischemia-reperfusion injury.

PubMed

Neeff, Hannes P; Sommer, Olaf; Meyer, Sebastian; Tinelli, Anja; Scholtes, Moritz; Hopt, Ulrich T; Drognitz, Oliver; von Dobschuetz, Ernst

2012-10-01

Reason for the unsuccessful use of antioxidants in transplantation might be the unknown kinetics of reactive oxygen species (ROS) release. In this study, we compared the kinetics of ROS release from rat pancreata in the presence and absence of blood. In vivo, ischemia-reperfusion injury (IRI) was induced in pancreata of male Wistar rats by occlusion of the arterial blood supply for 1 or 2 hours. In vitro, isolated pancreata were single-pass perfused with Krebs-Henseleit bicarbonate solution. Reactive oxygen species were quantified by electron spin resonance spectroscopy using CMH (1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine) as spin label. Thiols (glutathione), nicotinamide adenine dinucleotide phosphate-oxidase activity, myeloperoxidase activity, and adenosine triphosphate content were measured. During reperfusion, an increase in IRI-induced ROS in arterial blood was noted after 2 hours of warm ischemia. In sharp contrast, ROS release was immediate and short lived in blood-free perfused organs. The degree of tissue damage correlated with nicotinamide adenine dinucleotide phosphate-oxidase activity and adenosine triphosphate content. Antioxidative capacity of tissues was reduced. Electron spin resonance spectroscopy in conjunction with spin labels allows for the detection of ROS kinetics in pancreatic IRI. Reactive oxygen species kinetics are dependent on the length of the ischemic period and the presence or absence of blood.

Kinetic release of hydrogen peroxide from different whitening products.

PubMed

da Silva Marques, Duarte Nuno; Silveira, Joao Miguel; Marques, Joana Rita; Amaral, Joao Almeida; Guilherme, Nuno Marques; da Mata, António Duarte

2012-01-01

The objective of this in vitro study was to evaluate the kinetics of hydrogen peroxide (HP) release from five different bleaching products: VivaStyle® 10% fitted tray gel, VivaStyle® 30% in-office bleaching gel, VivaStyle® Paint-On Plus paint-on bleaching varnish, Opalescence PF® 10% carbamide peroxide gel and Trèswhite Supreme™ 10% HP gel. Each product was firstly titrated for its HP content by a described method. HP release kinetics was assessed by a modified spectrophotometric technique. One sample t test was performed to test for differences between the manufacturers' claimed HP concentrations and the titrated HP content in the whitening products. Analysis of variance plus Tamhane's post hoc tests and Pearson correlation analysis were used as appropriate. Values of P < 0.05 were taken as significant. Titrated HP revealed an increased content when compared to the manufacturer's specifications for all the products tested (P < 0.05), although only products from one manufacturer produced significantly higher results. All products presented a significant (P < 0.05) and sustained release of HP. However, the product with paint-on cellulose-based matrix resulted in significantly (P < 0.05) faster kinetics when compared to other products tested. These results are consistent with manufacturers' reduced recommended application times. The results of this study suggest that modifying the matrix composition may be a viable alternative to HP concentration increase, since this may result in faster release kinetics without exposure to high HP concentrations.

Passive neutralization of acid mine drainage using basic oxygen furnace slag as neutralization material: experimental and modelling.

PubMed

Zvimba, John N; Siyakatshana, Njabulo; Mathye, Matlhodi

2017-03-01

This study investigated passive neutralization of acid mine drainage using basic oxygen furnace slag as neutralization material over 90 days, with monitoring of the parameters' quality and assessment of their removal kinetics. The quality was observed to significantly improve over time with most parameters removed from the influent during the first 10 days. In this regard, removal of acidity, Fe(II), Mn, Co, Ni and Zn was characterized by fast kinetics while removal kinetics for Mg and SO 4 2- were observed to proceed slowly. The fast removal kinetics of acidity was attributed to fast release of alkalinity from slag minerals under mildly acidic conditions of the influent water. The removal of acidity through generation of alkalinity from the passive treatment system was also observed to generally govern the removal of metallic parameters through hydroxide formation, with overall percentage removals of 88-100% achieved. The removal kinetics for SO 4 2- was modelled using two approaches, yielding rate constant values of 1.56 and 1.53 L/(day mol) respectively, thereby confirming authenticity of SO 4 2- removal kinetics experimental data. The study findings provide insights into better understanding of the potential use of slags and their limitations, particularly in mine closure, as part of addressing this challenge in South Africa.

Mechanistic study of manganese-substituted glycerol dehydrogenase using a kinetic and thermodynamic analysis.

PubMed

Fang, Baishan; Niu, Jin; Ren, Hong; Guo, Yingxia; Wang, Shizhen

2014-01-01

Mechanistic insights regarding the activity enhancement of dehydrogenase by metal ion substitution were investigated by a simple method using a kinetic and thermodynamic analysis. By profiling the binding energy of both the substrate and product, the metal ion's role in catalysis enhancement was revealed. Glycerol dehydrogenase (GDH) from Klebsiella pneumoniae sp., which demonstrated an improvement in activity by the substitution of a zinc ion with a manganese ion, was used as a model for the mechanistic study of metal ion substitution. A kinetic model based on an ordered Bi-Bi mechanism was proposed considering the noncompetitive product inhibition of dihydroxyacetone (DHA) and the competitive product inhibition of NADH. By obtaining preliminary kinetic parameters of substrate and product inhibition, the number of estimated parameters was reduced from 10 to 4 for a nonlinear regression-based kinetic parameter estimation. The simulated values of time-concentration curves fit the experimental values well, with an average relative error of 11.5% and 12.7% for Mn-GDH and GDH, respectively. A comparison of the binding energy of enzyme ternary complex for Mn-GDH and GDH derived from kinetic parameters indicated that metal ion substitution accelerated the release of dioxyacetone. The metal ion's role in catalysis enhancement was explicated.

Sustained Release of Naproxen in a New Kind Delivery System of Carbon Nanotubes Hydrogel

PubMed Central

Peng, Xiahui; Zhuang, Qiang; Peng, Dongming; Dong, Qiuli; Tan, Lini; Jiao, Feipeng; Liu, Linqi; Liu, jingyu; Zhao, Chenxi; Wang, Xiaomei

2013-01-01

In this paper, carbon nanotubes (CNTs) were added into chitosan (CS) hydrogels in the form of chitosan modified CNTs (CS-CNTs) composites to prepare carbon nanotubes hydrogels (CNTs-GEL). The products, named CS-MWCNTs, were characterized by scanning electron microscope (SEM) and Fourier transform infrared (FTIR) spectroscopy. Swelling properties and effect of pH on controlled release performance of the two kinds of hydrogels, CNTs- GEL and pure chitosan hydrogels without CNTs (GEL), were investigated respectively. The results showed that CNTs-GEL possess better controlled release performance than GEL. The releasing equilibrium time of CNTs-GEL was longer than that of GEL in both pH = w7.4 and pH=1.2 conditions, although the release ratios of the model drug are similar in the same pH buffer solutions. It is found that release kinetics is better fitted Ritger-Peppas empirical model indicating a fick-diffusion process in pH = 1.2, while in pH = 7.4 it was non-fick diffusion involving surface diffusion and corrosion diffusion processes. PMID:24523738

Air oxidation of Zircaloy-4 in the 600-1000 °C temperature range: Modeling for ASTEC code application

NASA Astrophysics Data System (ADS)

Coindreau, O.; Duriez, C.; Ederli, S.

2010-10-01

Progress in the treatment of air oxidation of zirconium in severe accident (SA) codes are required for a reliable analysis of severe accidents involving air ingress. Air oxidation of zirconium can actually lead to accelerated core degradation and increased fission product release, especially for the highly-radiotoxic ruthenium. This paper presents a model to simulate air oxidation kinetics of Zircaloy-4 in the 600-1000 °C temperature range. It is based on available experimental data, including separate-effect experiments performed at IRSN and at Forschungszentrum Karlsruhe. The kinetic transition, named "breakaway", from a diffusion-controlled regime to an accelerated oxidation is taken into account in the modeling via a critical mass gain parameter. The progressive propagation of the locally initiated breakaway is modeled by a linear increase in oxidation rate with time. Finally, when breakaway propagation is completed, the oxidation rate stabilizes and the kinetics is modeled by a linear law. This new modeling is integrated in the severe accident code ASTEC, jointly developed by IRSN and GRS. Model predictions and experimental data from thermogravimetric results show good agreement for different air flow rates and for slow temperature transient conditions.

Development of Novel Warfarin-Silica Composite for Controlled Drug Release.

PubMed

Parfenyuk, Elena V; Dolinina, Ekaterina S

2017-04-01

The work is devoted to synthesis and study of warfarin composites with unmodified, methyl and phenyl modified silica in order to develop controlled release formulation of the anticoagulant. The composites were prepared by two routes, adsorption and sol-gel, and characterized with FTIR spectroscopy, dynamic light scattering and DSC methods. The drug release behavior from the composites in media with pH 1.6, 6.8 and 7.4 was analyzed in vitro. The release kinetics of the warfarin - silica composites prepared by the two routes was compared among each other and with analogous silica composites with water soluble drug molsidomine. The comparative analysis showed that in general the kinetic regularities and mechanisms of release for both drugs are similar and determined by nonuniform distribution of the drugs over the silica matrixes and stability of the matrixes in the studied media for the adsorbed composites and uniformly distributed drug and more brittle structure for the sol-gel composites. The sol-gel composite of warfarin - phenyl modified silica is perspective for further development of novel warfarin formulation with controlled release because it releases warfarin according to zero-order kinetic law with approximately equal rate in the media imitating different segments of gastrointestinal tract.

Use of fly ash, phosphogypsum and red mud as a liner material for the disposal of hazardous zinc leach residue waste.

PubMed

Coruh, Semra; Ergun, Osman Nuri

2010-01-15

Increasing amounts of residues and waste materials coming from industrial activities in different processes have become an increasingly urgent problem for the future. The release of large quantities of heavy metals into the environment has resulted in a number of environmental problems. The present study investigated the safe disposal of the zinc leach residue waste using industrial residues such as fly ash, phosphogypsum and red mud. In the study, leachability of heavy metals from the zinc leach residue has been evaluated by mine water leaching procedure (MWLP) and toxicity characteristic leaching procedure (TCLP). Zinc removal from leachate was studied using fly ash, phosphogypsum and red mud. The adsorption capacities and adsorption efficiencies were determined. The adsorption rate data was analyzed according to the pseudo-second-order kinetic, Elovich kinetic and intra-particle diffusion kinetic models. The pseudo-second-order kinetic was the best fit kinetic model for the experimental data. The results show that addition of fly ash, phosphogypsum and red mud to the zinc leach residue drastically reduces the heavy metal content in the leachate and could be used as liner materials.

Yield of reversible colloidal gels during flow start-up: release from kinetic arrest.

PubMed

Johnson, Lilian C; Landrum, Benjamin J; Zia, Roseanna N

2018-06-05

Yield of colloidal gels during start-up of shear flow is characterized by an overshoot in shear stress that accompanies changes in network structure. Prior studies of yield of reversible colloidal gels undergoing strong flow model the overshoot as the point at which network rupture permits fluidization. However, yield under weak flow, which is of interest in many biological and industrial fluids shows no such disintegration. The mechanics of reversible gels are influenced by bond strength and durability, where ongoing rupture and re-formation impart aging that deepens kinetic arrest [Zia et al., J. Rheol., 2014, 58, 1121], suggesting that yield be viewed as release from kinetic arrest. To explore this idea, we study reversible colloidal gels during start-up of shear flow via dynamic simulation, connecting rheological yield to detailed measurements of structure, bond dynamics, and potential energy. We find that pre-yield stress grows temporally with the changing roles of microscopic transport processes: early time behavior is set by Brownian diffusion; later, advective displacements permit relative particle motion that stretches bonds and stores energy. Stress accumulates in stretched, oriented bonds until yield, which is a tipping point to energy release, and is passed with a fully intact network, where the loss of very few bonds enables relaxation of many, easing glassy arrest. This is immediately followed by a reversal to growth in potential energy during bulk plastic deformation and condensation into larger particle domains, supporting the view that yield is an activated release from kinetic arrest. The continued condensation of dense domains and shrinkage of network surfaces, along with a decrease in the potential energy, permit the gel to evolve toward more complete phase separation, supporting our view that yield of weakly sheared gels is a 'non-equilibrium phase transition'. Our findings may be particularly useful for industrial or other coatings, where weak, slow application via shear may lead to phase separation, inhibiting smooth distribution.

A study of chitosan hydrogel with embedded mesoporous silica nanoparticles loaded by ibuprofen as a dual stimuli-responsive drug release system for surface coating of titanium implants.

PubMed

Zhao, Pengkun; Liu, Hongyu; Deng, Hongbing; Xiao, Ling; Qin, Caiqin; Du, Yumin; Shi, Xiaowen

2014-11-01

In this study, the complex pH and electro responsive system made of chitosan hydrogel with embedded mesoporous silica nanoparticles (MSNs) was evaluated as a tunable drug release system. As a model drug, ibuprofen (IB) was used; its adsorption in MSNs was evidenced by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM) and thermogravimetric analysis (TG). In order to prepare the complex drug release system, the loaded particles IB-MSNs were dispersed in chitosan solution and then the complex IB-MSNs/chitosan film of 2mm thickness was deposited as a hydrogel on the titanium electrode. The codeposition of components was performed under a negative biasing of the titanium electrode at -0.75 mA/cm2 current density during 30 min. The IB release from the IB-MSNs/chitosan hydrogel film was studied as dependent on pH of the release media and electrical conditions applied to the titanium plate. When incubating the complex hydrogel film in buffers with different pH, the IB release followed a near zero-order profile, though its kinetics varied. Compared to the spontaneous IB release from the hydrogel in 0.9% NaCl solution (at 0 V), the application of negative biases to the coated titanium plate had profound effluences on the release behavior. The release was retarded when -1.0 V was applied, but a faster kinetics was observed at -5.0 V. These results imply that a rapid, mild and facile electrical process for covering titanium implants by complex IB-MSNs/chitosan hydrogel films can be used for controlled drug delivery applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of two hydrophobic polymers on the release of gliclazide from their matrix tablets.

PubMed

Hussain, Talib; Saeed, Tariq; Mumtaz, Ahmad M; Javaid, Zeeshan; Abbas, Khizar; Awais, Azeema; Idrees, Hafiz Arfat

2013-01-01

Gliclazide is an oral hypoglycemic agent, indicated in non insulin dependent diabetes mellitus and in patients with diabetic retinopathy. It has good tolerability and is a short acting sulfonyl urea that requires large dose to maintain the blood glucose level. So development of a sustained release formulation of gliclazide (GLZ) is required for better patient compliance. This study was conducted to assess the effects of different drug polymer ratios on the release profile of gliclazide from the matrix. Oral matrix tablets of gliclazide were prepared by hot melt method, using pure and blended mixture of glyceryl monostearate (GMS) and stearic acid (SA) in different ratios. In vitro release pattern was studied for 8 h in phosphate buffer media (pH 7.4). Different kinetic models including zero order, first order, Higuchi and Peppas were applied to evaluate drug release behavior. Drug excipient compatibility was evaluated by scanning with DSC and FTIR. Higuchi model was found the most appropriate model for describing the release profile of GLZ and non-Fickian release was found predominant mechanism of drug release. The release of drug from the matrix was greatly controlled by GMS while SA appeared to facilitate the release of drug from matrix tablets. FTIR results showed no chemical interaction between drug and the polymers, and DSC results indicated amorphous state of GLZ and polymers without significant complex formation. The results indicate that matrix tablets of gliclazide using glyceryl monostearate and stearic acid showed marked sustained release properties.

Drug release from slabs and the effects of surface roughness.

PubMed

Kalosakas, George; Martini, Dimitra

2015-12-30

We discuss diffusion-controlled drug release from slabs or thin films. Analytical and numerical results are presented for slabs with flat surfaces, having a uniform thickness. Then, considering slabs with rough surfaces, the influence of a non-uniform slab thickness on release kinetics is numerically investigated. The numerical release profiles are obtained using Monte Carlo simulations. Release kinetics is quantified through the stretched exponential (or Weibull) function and the resulting dependence of the two parameters of this function on the thickness of the slab, for flat surfaces, and the amplitude of surface fluctuations (or the degree of thickness variability) in case of roughness. We find that a higher surface roughness leads to a faster drug release. Copyright © 2015 Elsevier B.V. All rights reserved.

Encapsulation of Volatile Citronella Essential Oil by Coacervation: Efficiency and Release Study

NASA Astrophysics Data System (ADS)

Manaf, M. A.; Subuki, I.; Jai, J.; Raslan, R.; Mustapa, A. N.

2018-05-01

The volatile citronella essential oil was encapsulated by simple coacervation and complex coacervation using Arabic gum and gelatin as wall material. Glutaraldehyde was used in the methodology as crosslinking agent. The citronella standard calibration graph obtained with R2 of 0.9523 was used for the accurate determination of encapsulation efficiency and release study. The release kinetic was analysed based on Fick"s law of diffusion for polymeric system and linear graph of Log fraction release over Log time was constructed to determine the release rate constant, k and diffusion coefficient, n. Both coacervation methods in the present study produce encapsulation efficiency around 94%. The produced capsules for both coacervation processes were discussed based on the capsules morphology and release kinetic mechanisms.

The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants

PubMed Central

Yassin, Samy; Goodwin, Daniel J; Anderson, Andrew; Sibik, Juraj; Wilson, D Ian; Gladden, Lynn F; Zeitler, J Axel

2015-01-01

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3440–3450, 2015 PMID:26073446

Ab initio calculations and kinetic modeling of thermal conversion of methyl chloride: implications for gasification of biomass.

PubMed

Singla, Mallika; Rasmussen, Morten Lund; Hashemi, Hamid; Wu, Hao; Glarborg, Peter; Pelucchi, Matteo; Faravelli, Tiziano; Marshall, Paul

2018-04-25

Limitations in current hot gas cleaning methods for chlorine species from biomass gasification may be a challenge for end use such as gas turbines, engines, and fuel cells, all requiring very low levels of chlorine. During devolatilization of biomass, chlorine is released partly as methyl chloride. In the present work, the thermal conversion of CH3Cl under gasification conditions was investigated. A detailed chemical kinetic model for pyrolysis and oxidation of methyl chloride was developed and validated against selected experimental data from the literature. Key reactions of CH2Cl with O2 and C2H4 for which data are scarce were studied by ab initio methods. The model was used to analyze the fate of methyl chloride in gasification processes. The results indicate that CH3Cl emissions will be negligible for most gasification technologies, but could be a concern for fluidized bed gasifiers, in particular in low-temperature gasification. The present work illustrates how ab initio theory and chemical kinetic modeling can help to resolve emission issues for thermal processes in industrial scale.

Development and evaluation of controlled porosity osmotic pump for Nifedipine and Metoprolol combination

PubMed Central

2011-01-01

Background A system that can deliver multi-drug at a prolonged rate is very important for the treatment of various chronic diseases such as diabetes, asthma and heart disease. Controlled porosity osmotic pump tablet (CPOP) system was designed to deliver Nifedipine (NP) and Metoprolol (MP) in a controlled manner up to 12 h. It was prepared by incorporating drugs in the core and coated with various types (PVP, PEG-400 and HPMC) and levels (30, 40 and 50% w/w of polymer) of pore former at a weight gain of 8, 12 & 15%. Results Formulation variables like type and level of pore former and percent weight gain of membrane was found to affect the drug release from the developed formulations. Drug release was inversely proportional to the membrane weight but directly related to the level of pore former. Burst strength of the exhausted shell was inversely proportional to the level of pore former, but directly affected by the membrane weight. Results of scanning electron microscopy (SEM) studies showed the formation of pores in the membrane from where the drug release occurred. Dissolution models were applied to drug release data in order to establish the mechanism of drug release kinetics. In vitro release kinetics was subjected to superposition method to predict in vivo performance of the developed formulation. Conclusion The developed osmotic system is effective in the multi-drug therapy of hypertension by delivering both drugs in a controlled manner. PMID:21477386

Physicochemical characterization and mechanisms of release of theophylline from melt-extruded dosage forms based on a methacrylic acid copolymer.

PubMed

Young, Christopher R; Dietzsch, Caroline; Cerea, Matteo; Farrell, Thomas; Fegely, Kurt A; Rajabi-Siahboomi, Ali; McGinity, James W

2005-09-14

The purpose of the current study was to investigate the physicochemical properties of melt-extruded dosage forms based on Acryl-EZE and to determine the influence of gelling agents on the mechanisms and kinetics of drug release from thermally processed matrices. Acryl-EZE is a pre-mixed excipient blend based on a methacrylic acid copolymer that is optimized for film-coating applications. Powder blends containing theophylline, Acryl-EZE, triethyl citrate and an optional gelling agent, Methocel K4M Premium (hydroxypropyl methylcellulose, HPMC, hypromellose 2208) or Carbopol 974P (carbomer), were thermally processed using a Randcastle single-screw extruder. The physical and chemical stability of materials during processing was determined using thermal gravimetric analysis and HPLC. The mechanism of drug release was determined using the Korsmeyer-Peppas model and the hydration and erosion of tablets during the dissolution studies were investigated. The excipient blends were physically and chemically stable during processing, and the resulting dosage forms exhibited pH-dependent dissolution properties. Extrusion of blends containing HPMC or carbomer changed the mechanism and kinetics of drug release from the thermally processed dosage forms. At concentrations of 5% or below, carbomer was more effective than HPMC at extending the duration of theophylline release from matrix tablets. Furthermore, carbomer containing tablets were stable upon storage for 3 months at 40 degrees C/75% RH. Thus, hot-melt extrusion was an effective process for the preparation of controlled release matrix systems based on Acryl-EZE.

Composite Magnetite and Protein Containing CaCO3 Crystals. External Manipulation and Vaterite → Calcite Recrystallization-Mediated Release Performance.

PubMed

Sergeeva, Alena; Sergeev, Roman; Lengert, Ekaterina; Zakharevich, Andrey; Parakhonskiy, Bogdan; Gorin, Dmitry; Sergeev, Sergey; Volodkin, Dmitry

2015-09-30

Biocompatibility and high loading capacity of mesoporous CaCO3 vaterite crystals give an option to utilize the polycrystals for a wide range of (bio)applications. Formation and transformations of calcium carbonate polymorphs have been studied for decades, aimed at both basic and applied research interests. Here, composite multilayer-coated calcium carbonate polycrystals containing Fe3O4 magnetite nanoparticles and model protein lysozyme are fabricated. The structure of the composite polycrystals and vaterite → calcite recrystallization kinetics are studied. The recrystallization results in release of both loaded protein and Fe3O4 nanoparticles (magnetic manipulation is thus lost). Fe3O4 nanoparticles enhance the recrystallization that can be induced by reduction of the local pH with citric acid and reduction of the polycrystal crystallinity. Oppositely, the layer-by-layer assembled poly(allylamine hydrochloride)/poly(sodium styrenesulfonate) polyelectrolyte coating significantly inhibits the vaterite → calcite recrystallization (from hours to days) most likely due to suppression of the ion exchange giving an option to easily tune the release kinetics for a wide time scale, for example, for prolonged release. Moreover, the recrystallization of the coated crystals results in formulation of multilayer capsules keeping the feature of external manipulation. This study can help to design multifunctional microstructures with tailor-made characteristics for loading and controlled release as well as for external manipulation.

Turbulent Kinetic Energy in the Energy Balance of a Solar Flare

NASA Astrophysics Data System (ADS)

Kontar, E. P.; Perez, J. E.; Harra, L. K.; Kuznetsov, A. A.; Emslie, A. G.; Jeffrey, N. L. S.; Bian, N. H.; Dennis, B. R.

2017-04-01

The energy released in solar flares derives from a reconfiguration of magnetic fields to a lower energy state, and is manifested in several forms, including bulk kinetic energy of the coronal mass ejection, acceleration of electrons and ions, and enhanced thermal energy that is ultimately radiated away across the electromagnetic spectrum from optical to x rays. Using an unprecedented set of coordinated observations, from a suite of instruments, we here report on a hitherto largely overlooked energy component—the kinetic energy associated with small-scale turbulent mass motions. We show that the spatial location of, and timing of the peak in, turbulent kinetic energy together provide persuasive evidence that turbulent energy may play a key role in the transfer of energy in solar flares. Although the kinetic energy of turbulent motions accounts, at any given time, for only ˜(0.5 - 1 )% of the energy released, its relatively rapid (˜1 - 10 s ) energization and dissipation causes the associated throughput of energy (i.e., power) to rival that of major components of the released energy in solar flares, and thus presumably in other astrophysical acceleration sites.

Turbulent Kinetic Energy in the Energy Balance of a Solar Flare.

PubMed

Kontar, E P; Perez, J E; Harra, L K; Kuznetsov, A A; Emslie, A G; Jeffrey, N L S; Bian, N H; Dennis, B R

2017-04-14

The energy released in solar flares derives from a reconfiguration of magnetic fields to a lower energy state, and is manifested in several forms, including bulk kinetic energy of the coronal mass ejection, acceleration of electrons and ions, and enhanced thermal energy that is ultimately radiated away across the electromagnetic spectrum from optical to x rays. Using an unprecedented set of coordinated observations, from a suite of instruments, we here report on a hitherto largely overlooked energy component-the kinetic energy associated with small-scale turbulent mass motions. We show that the spatial location of, and timing of the peak in, turbulent kinetic energy together provide persuasive evidence that turbulent energy may play a key role in the transfer of energy in solar flares. Although the kinetic energy of turbulent motions accounts, at any given time, for only ∼(0.5-1)% of the energy released, its relatively rapid (∼1-10  s) energization and dissipation causes the associated throughput of energy (i.e., power) to rival that of major components of the released energy in solar flares, and thus presumably in other astrophysical acceleration sites.

Modeling of the dispersion of depleted uranium aerosol.

PubMed

Mitsakou, C; Eleftheriadis, K; Housiadas, C; Lazaridis, M

2003-04-01

Depleted uranium is a low-cost radioactive material that, in addition to other applications, is used by the military in kinetic energy weapons against armored vehicles. During the Gulf and Balkan conflicts concern has been raised about the potential health hazards arising from the toxic and radioactive material released. The aerosol produced during impact and combustion of depleted uranium munitions can potentially contaminate wide areas around the impact sites or can be inhaled by civilians and military personnel. Attempts to estimate the extent and magnitude of the dispersion were until now performed by complex modeling tools employing unclear assumptions and input parameters of high uncertainty. An analytical puff model accommodating diffusion with simultaneous deposition is developed, which can provide a reasonable estimation of the dispersion of the released depleted uranium aerosol. Furthermore, the period of the exposure for a given point downwind from the release can be estimated (as opposed to when using a plume model). The main result is that the depleted uranium mass is deposited very close to the release point. The deposition flux at a couple of kilometers from the release point is more than one order of magnitude lower than the one a few meters near the release point. The effects due to uncertainties in the key input variables are addressed. The most influential parameters are found to be atmospheric stability, height of release, and wind speed, whereas aerosol size distribution is less significant. The output from the analytical model developed was tested against the numerical model RPM-AERO. Results display satisfactory agreement between the two models.

A General Model of Synaptic Transmission and Short-Term Plasticity

PubMed Central

Pan, Bin; Zucker, Robert S.

2011-01-01

SUMMARY Some synapses transmit strongly to action potentials (APs), but weaken with repeated activation; others transmit feebly at first, but strengthen with sustained activity. We measured synchronous and asynchronous transmitter release at “phasic” crayfish neuromuscular junctions (NMJs) showing depression and at facilitating “tonic” junctions, and define the kinetics of depression and facilitation. We offer a comprehensive model of presynaptic processes, encompassing mobilization of reserve vesicles, priming of docked vesicles, their association with Ca2+ channels, and refractoriness of release sites, while accounting for data on presynaptic buffers governing Ca2+ diffusion. Model simulations reproduce many experimentally defined aspects of transmission and plasticity at these synapses. Their similarity to vertebrate central synapses suggests that the model might be of general relevance to synaptic transmission. PMID:19477155

Relationship between Surface Properties and In Vitro Drug Release from Compressed Matrix Containing Polymeric Materials with Different Hydrophobicity Degrees

PubMed Central

Yarce, Cristhian J.; Echeverri, Juan D.; Palacio, Mario A.; Rivera, Carlos A.; Salamanca, Constain H.

2017-01-01

This work is the continuation of a study focused on establishing relations between surface thermodynamic properties and in vitro release mechanisms using a model drug (ampicillin trihydrate), besides analyzing the granulometric properties of new polymeric materials and thus establishing the potential to be used in the pharmaceutical field as modified delivery excipients. To do this, we used copolymeric materials derived from maleic anhydride with decreasing polarity corresponding to poly(isobutylene-alt-maleic acid) (hydrophilic), sodium salt of poly(maleic acid-alt-octadecene) (amphiphilic), poly(maleic anhydride-alt-octadecene) (hydrophobic) and the reference polymer hydroxyl-propyl-methyl-cellulose (HPMC). Each material alone and in blends underwent spectroscopic characterization by FTIR, thermal characterization by DSC and granulometric characterization using flow and compaction tests. Each tablet was prepared at different polymer ratios of 0%, 10%, 20%, 30% and 40%, and the surface properties were determined, including the roughness by micro-visualization, contact angle and water absorption rate by the sessile drop method and obtaining Wadh and surface free energy (SFE) using the semi-empirical models of Young–Dupré and  Owens-Wendt-Rabel-Käelbe (OWRK), respectively. Dissolution profiles were determined simulating physiological conditions in vitro, where the kinetic models of order-zero, order-one, Higuchi and Korsmeyer–Peppas were evaluated. The results showed a strong relationship between the proportion and nature of the polymer to the surface thermodynamic properties and kinetic release mechanism. PMID:28125020

Model Validation for Propulsion - On the TFNS and LES Subgrid Models for a Bluff Body Stabilized Flame

NASA Technical Reports Server (NTRS)

Wey, Thomas

2017-01-01

This paper summarizes the reacting results of simulating a bluff body stabilized flame experiment of Volvo Validation Rig using a releasable edition of the National Combustion Code (NCC). The turbulence models selected to investigate the configuration are the sub-grid scaled kinetic energy coupled large eddy simulation (K-LES) and the time-filtered Navier-Stokes (TFNS) simulation. The turbulence chemistry interaction used is linear eddy mixing (LEM).

Influences of pH and CO2 on the formation of Metasilicate mineral water in Changbai Mountain, Northeast China

NASA Astrophysics Data System (ADS)

Yan, Baizhong; Xiao, Changlai; Liang, Xiujuan; Wu, Shili

2017-07-01

Mineral dissolution reactions actively participate in controlling the composition of mineral water. In this study, water soluble, acidic-alkaline and carbonated solution experiments were designed, and mineral reaction mechanisms were researched using chemical kinetics and the minimum free-energy method. The results showed that the release of metasilicate was controlled by pH, CO2, and rock characteristics. In the water soluble experiment, the release process of metasilicate in powdered rocks reached equilibrium after 40 days, while metasilicate in solid rocks took 170 days. The release process of metasilicate in solid rocks satisfied an asymptotic model, while in powdered rocks it accorded with the Stanford reaction kinetic model. In the acidic-alkaline experiment, metasilicate was released earlier under acidic conditions (2.46 < pH < 7) than under alkaline conditions (7 < pH < 10.61). The release process of metasilicate under acidic conditions reached equilibrium in 40 days, compared with 60 days for alkaline conditions. The addition of CO2 to the water solution was beneficial to the formation of metasilicate. Under neutral pH conditions, the reaction barely occurred. Under alkaline conditions, metasilicate was produced by the hydrolysis of metasilicate minerals. Under acidic and additional CO2 conditions, metasilicate formation was mainly via the reaction of H+, CO2, and metasilicate minerals. From these results, we concluded that the metasilicate mineral water from the Changbai Mountains, Jingyu County, is generated by a combination of the hydrolysis of metasilicate minerals and the reaction of H+, CO2, and metasilicate minerals. These results can contribute to a better development and protection of the mineral water resources in the Changbai Mountains.

Bioerodible System for Sequential Release of Multiple Drugs

PubMed Central

Sundararaj, Sharath C.; Thomas, Mark V.; Dziubla, Thomas D.; Puleo, David A.

2013-01-01

Because many complex physiological processes are controlled by multiple biomolecules, comprehensive treatment of certain disease conditions may be more effectively achieved by administration of more than one type of drug. Thus, the objective of the present research was to develop a multilayered, polymer-based system for sequential delivery of multiple drugs. The polymers used were cellulose acetate phthalate (CAP) complexed with Pluronic F-127 (P). After evaluating morphology of the resulting CAPP system, in vitro release of small molecule drugs and a model protein was studied from both single and multilayered devices. Drug release from single-layered CAPP films followed zero-order kinetics related to surface erosion of the association polymer. Release studies from multilayered CAPP devices showed the possibility of achieving intermittent release of one type of drug as well as sequential release of more than one type of drug. Mathematical modeling accurately predicted the release profiles for both single layer and multilayered devices. The present CAPP association polymer-based multilayer devices can be used for localized, sequential delivery of multiple drugs for the possible treatment of complex disease conditions, and perhaps for tissue engineering applications, that require delivery of more than one type of biomolecule. PMID:24096151

Transgenic mouse α- and β-cardiac myosins containing the R403Q mutation show isoform-dependent transient kinetic differences.

PubMed

Lowey, Susan; Bretton, Vera; Gulick, James; Robbins, Jeffrey; Trybus, Kathleen M

2013-05-24

Familial hypertrophic cardiomyopathy (FHC) is a major cause of sudden cardiac death in young athletes. The discovery in 1990 that a point mutation at residue 403 (R403Q) in the β-myosin heavy chain (MHC) caused a severe form of FHC was the first of many demonstrations linking FHC to mutations in muscle proteins. A mouse model for FHC has been widely used to study the mechanochemical properties of mutated cardiac myosin, but mouse hearts express α-MHC, whereas the ventricles of larger mammals express predominantly β-MHC. To address the role of the isoform backbone on function, we generated a transgenic mouse in which the endogenous α-MHC was partially replaced with transgenically encoded β-MHC or α-MHC. A His6 tag was cloned at the N terminus, along with R403Q, to facilitate isolation of myosin subfragment 1 (S1). Stopped flow kinetics were used to measure the equilibrium constants and rates of nucleotide binding and release for the mouse S1 isoforms bound to actin. For the wild-type isoforms, we found that the affinity of MgADP for α-S1 (100 μM) is ~ 4-fold weaker than for β-S1 (25 μM). Correspondingly, the MgADP release rate for α-S1 (350 s(-1)) is ~3-fold greater than for β-S1 (120 s(-1)). Introducing the R403Q mutation caused only a minor reduction in kinetics for β-S1, but R403Q in α-S1 caused the ADP release rate to increase by 20% (430 s(-1)). These transient kinetic studies on mouse cardiac myosins provide strong evidence that the functional impact of an FHC mutation on myosin depends on the isoform backbone.

HPMA-based block copolymers promote differential drug delivery kinetics for hydrophobic and amphiphilic molecules.

PubMed

Tomcin, Stephanie; Kelsch, Annette; Staff, Roland H; Landfester, Katharina; Zentel, Rudolf; Mailänder, Volker

2016-04-15

We describe a method how polymeric nanoparticles stabilized with (2-hydroxypropyl)methacrylamide (HPMA)-based block copolymers are used as drug delivery systems for a fast release of hydrophobic and a controlled release of an amphiphilic molecule. The versatile method of the miniemulsion solvent-evaporation technique was used to prepare polystyrene (PS) as well as poly-d/l-lactide (PDLLA) nanoparticles. Covalently bound or physically adsorbed fluorescent dyes labeled the particles' core and their block copolymer corona. Confocal laser scanning microscopy (CLSM) in combination with flow cytometry measurements were applied to demonstrate the burst release of a fluorescent hydrophobic drug model without the necessity of nanoparticle uptake. In addition, CLSM studies and quantitative calculations using the image processing program Volocity® show the intracellular detachment of the amphiphilic block copolymer from the particles' core after uptake. Our findings offer the possibility to combine the advantages of a fast release for hydrophobic and a controlled release for an amphiphilic molecule therefore pointing to the possibility to a 'multi-step and multi-site' targeting by one nanocarrier. We describe thoroughly how different components of a nanocarrier end up in cells. This enables different cargos of a nanocarrier having a consecutive release and delivery of distinct components. Most interestingly we demonstrate individual kinetics of distinct components of such a system: first the release of a fluorescent hydrophobic drug model at contact with the cell membrane without the necessity of nanoparticle uptake. Secondly, the intracellular detachment of the amphiphilic block copolymer from the particles' core after uptake occurs. This offers the possibility to combine the advantages of a fast release for a hydrophobic substance at the time of interaction of the nanoparticle with the cell surface and a controlled release for an amphiphilic molecule later on therefore pointing to the possibility to a 'multi-step and multisite' targeting by one nanocarrier. We therefore feel that this could be used for many cellular systems where the combined and orchestrated delivery of components is prerequisite in order to obtain the highest efficiency. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Release mechanism of insulin encapsulated in trehalose ester derivative microparticles delivered via inhalation.

PubMed

Davidson, Iain G; Langner, Eric J; Plowman, Steven V; Blair, Julian A

2003-03-26

The aim of this study was to evaluate properties of amorphous oligosaccharide ester derivative (OED) microparticles in order to determine drug release mechanisms in the lung. Trehalose OEDs with a wide range of properties were synthesised using conventional methods. The interaction of spray dried amorphous microparticles (2-3 microm) with water was investigated using attenuated total reflectance Fourier transform infra-red spectroscopy (ATR-FTIR) and dynamic vapour sorption (DVS). The in vivo performance of insulin/OED microparticles was assessed using a modified Higuchi kinetic model. A modified Hansen solvent parameter approach was used to analyse the interactions with water and in vivo trends. In water or high humidity, OED powders absorb water, lose relaxation energy and crystallise. The delay of the onset of crystallisation depends on the OED and the amount of water present. Crystallisation follows first order Arrhenius kinetics and release of insulin from OED microparticles closely matches the degree of crystallisation. The induction period depends on dispersive interactions between the OED and water while crystallisation is governed by polarity and hydrogen bonding. Drug release from OED microparticles is, therefore, controlled by crystallisation of the matrix on contact with water. The pulmonary environment was found to resemble one of high humidity rather than a liquid medium. Copyright 2003 Elsevier Science B.V.

Shear rheology and in-vitro release kinetic study of apigenin from lyotropic liquid crystal.

PubMed

Fan, Jun; Liu, Feng; Wang, Zhongni

2016-01-30

Apigenin is a flavonoid compound with diverse pharmacological functions which could develop health benefit products, but its formulation is hampered by its poor water solubility and bioavailability. In this paper, in order to overcome these difficulties, apigenin was encapsulated in LLC formed by polyoxyethylene-10-oleyl ether (Brij 97) and sodium deoxycholate (NaDC) mixtures. The hexagonal liquid crystalline phase (H) and the cubic liquid crystalline phase (C) were found in this system. The shear rheology was used to study the structure change with temperature. It was shown that C3 (Brij 97-NaDC/IPM-PEG400/H2O=36:9:55) was C at low temperature. But above 35.6°C, the matrix of C3 completely transformed to polymer solution. The matrix of H3 was H (Brij 97-NaDC:IPM-PEG 400:H2O=50:9:41) below 50°C, but the structural strength change was obvious. Vitro release experiment was used to study drug release kinetics. It was indicated that apigenin encapsulated in LLC conformed to the concentration diffusion model, and cumulative percentage of apigenin released from C3 and H3 had corresponding relationship with the shear rheology at different temperatures. Copyright © 2015. Published by Elsevier B.V.

Enhanced Healing of Rat Calvarial Defects with MSCs Loaded on BMP-2 Releasing Chitosan/Alginate/Hydroxyapatite Scaffolds

PubMed Central

He, Xiaoning; Liu, Yang; Yuan, Xue; Lu, Li

2014-01-01

In this study, we designed a chitosan/alginate/hydroxyapatite scaffold as a carrier for recombinant BMP-2 (CAH/B2), and evaluated the release kinetics of BMP-2. We evaluated the effect of the CAH/B2 scaffold on the viability and differentiation of bone marrow mesenchymal stem cells (MSCs) by scanning electron microscopy, MTS, ALP assay, alizarin-red staining and qRT-PCR. Moreover, MSCs were seeded on scaffolds and used in a 8 mm rat calvarial defect model. New bone formation was assessed by radiology, hematoxylin and eosin staining 12 weeks postoperatively. We found the release kinetics of BMP-2 from the CAH/B2 scaffold were delayed compared with those from collagen gel, which is widely used for BMP-2 delivery. The BMP-2 released from the scaffold increased MSC differentiation and did not show any cytotoxicity. MSCs exhibited greater ALP activity as well as stronger calcium mineral deposition, and the bone-related markers Col1α, osteopontin, and osteocalcin were upregulated. Analysis of in vivo bone formation showed that the CAH/B2 scaffold induced more bone formation than other groups. This study demonstrates that CAH/B2 scaffolds might be useful for delivering osteogenic BMP-2 protein and present a promising bone regeneration strategy. PMID:25084008

Critical evaluation of Jet-A spray combustion using propane chemical kinetics in gas turbine combustion simulated by KIVA-2

NASA Technical Reports Server (NTRS)

Nguyen, H. L.; Ying, S.-J.

1990-01-01

Jet-A spray combustion has been evaluated in gas turbine combustion with the use of propane chemical kinetics as the first approximation for the chemical reactions. Here, the numerical solutions are obtained by using the KIVA-2 computer code. The KIVA-2 code is the most developed of the available multidimensional combustion computer programs for application of the in-cylinder combustion dynamics of internal combustion engines. The released version of KIVA-2 assumes that 12 chemical species are present; the code uses an Arrhenius kinetic-controlled combustion model governed by a four-step global chemical reaction and six equilibrium reactions. Researchers efforts involve the addition of Jet-A thermophysical properties and the implementation of detailed reaction mechanisms for propane oxidation. Three different detailed reaction mechanism models are considered. The first model consists of 131 reactions and 45 species. This is considered as the full mechanism which is developed through the study of chemical kinetics of propane combustion in an enclosed chamber. The full mechanism is evaluated by comparing calculated ignition delay times with available shock tube data. However, these detailed reactions occupy too much computer memory and CPU time for the computation. Therefore, it only serves as a benchmark case by which to evaluate other simplified models. Two possible simplified models were tested in the existing computer code KIVA-2 for the same conditions as used with the full mechanism. One model is obtained through a sensitivity analysis using LSENS, the general kinetics and sensitivity analysis program code of D. A. Bittker and K. Radhakrishnan. This model consists of 45 chemical reactions and 27 species. The other model is based on the work published by C. K. Westbrook and F. L. Dryer.

Studies on the formation of polymeric nano-emulsions obtained via low-energy emulsification and their use as templates for drug delivery nanoparticle dispersions.

PubMed

Calderó, G; Montes, R; Llinàs, M; García-Celma, M J; Porras, M; Solans, C

2016-09-01

Ethylcellulose nanoparticles have been obtained from O/W nano-emulsions of the water/polyoxyethylene 10 oleyl ether/[ethyl acetate+4wt% ethylcellulose] system by low energy-energy emulsification at 25°C. Nano-emulsions with droplet sizes below 200nm and high kinetic stability were chosen for solubilising dexamethasone (DXM). Phase behaviour, conductivity and optical analysis studies of the system have evidenced for the first time that both, the polymer and the drug play a role on the structure of the aggregates formed along the emulsification path. Nano-emulsion formation may take place by both, phase inversion and self-emulsification. Spherical polymeric nanoparticles containing surfactant, showing sizes below 160nm have been obtained from the nano-emulsions by organic solvent evaporation. DXM loading in the nanoparticles was high (>90%). The release kinetics of nanoparticle dispersions with similar particle size and encapsulated DXM but different polymer to surfactant ratio were studied and compared to an aqueous DXM solution. Drug release from the nanoparticle dispersions was slower than from the aqueous solution. While the DXM solution showed a Fickian release pattern, the release behaviour from the nanoparticle dispersions was faster than that expected from a pure Fickian release. A coupled diffusion/relaxation model fitted the results very well, suggesting that polymer chains undergo conformational changes enhancing drug release. The contribution of diffusion and relaxation to drug transport in the nanoparticle dispersions depended on their composition and release time. Surfactant micelles present in the nanoparticle dispersion may exert a mild reservoir effect. The small particle size and the prolonged DXM release provided by the ethylcellulose nanoparticle dispersions make them suitable vehicles for controlled drug delivery applications. Copyright © 2016 Elsevier B.V. All rights reserved.

How to adjust desired drug release patterns from ethylcellulose-coated dosage forms.

PubMed

Siepmann, F; Hoffmann, A; Leclercq, B; Carlin, B; Siepmann, J

2007-06-04

The aim of this study was to provide an easy and efficient tool to adjust desired drug release kinetics from (aqueous) ethylcellulose-coated solid dosage forms and to better understand the underlying mass transport mechanisms. Pure ethylcellulose films are poorly permeable for many substances and can result in very low release rates for certain drugs from coated dosage forms, if the film coatings are completely formed and remain intact upon exposure to the release media. To increase the permeability of the polymeric membranes, different amounts of a water-soluble poly(vinyl alcohol)-poly(ethylene glycol) graft copolymer (PVA-PEG graft copolymer) were added to an aqueous ethylcellulose dispersion (Aquacoat ECD). Importantly, the presence of only a low percentage of this hydrophilic copolymer significantly increased the resulting water uptake rate and extent, dry weight loss and drug permeability of the films. In contrast to hydroxypropyl methylcellulose (HPMC), the PVA-PEG graft copolymer does not cause flocculation of the colloidal coating dispersion (leading to potentially variable release rates). Interestingly, the transport of water as well as of the model drug theophylline through the polymeric networks was primarily controlled by pure diffusion. The penetration kinetics could be quantitatively described by Fick's law of diffusion, irrespective of the type of release medium and PVA-PEG graft copolymer content. Most important from a practical point of view, a broad spectrum of pH-independent drug release rates can easily be obtained from drug-loaded pellets by simply varying the PVA-PEG graft copolymer content. An appropriate curing step after coating is required, but interestingly the investigated curing conditions (differing in time and relative humidity) resulted in very similar drug release patterns, indicating that stable film structures are likely to be achieved.

The relationship between Q gamma and Ca release from the sarcoplasmic reticulum in skeletal muscle

PubMed Central

1991-01-01

Asymmetric membrane currents and fluxes of Ca2+ release were determined in skeletal muscle fibers voltage clamped in a Vaseline-gap chamber. The conditioning pulse protocol 1 for suppressing Ca2+ release and the "hump" component of charge movement current (I gamma), described in the first paper of this series, was applied at different test pulse voltages. The amplitude of the current suppressed during the ON transient reached a maximum at slightly suprathreshold test voltages (- 50 to -40 mV) and decayed at higher voltages. The component of charge movement current suppressed by 20 microM tetracaine also went through a maximum at low pulse voltages. This anomalous voltage dependence is thus a property of I gamma, defined by either the conditioning protocol or the tetracaine effect. A negative (inward-going) phase was often observed in the asymmetric current during the ON of depolarizing pulses. This inward phase was shown to be an intramembranous charge movement based on (a) its presence in the records of total membrane current, (b) its voltage dependence, with a maximum at slightly suprathreshold voltages, (c) its association with a "hump" in the asymmetric current, (d) its inhibition by interventions that reduce the "hump", (e) equality of ON and OFF areas in the records of asymmetric current presenting this inward phase, and (f) its kinetic relationship with the time derivative of Ca release flux. The nonmonotonic voltage dependence of the amplitude of the hump and the possibility of an inward phase of intramembranous charge movement are used as the main criteria in the quantitative testing of a specific model. According to this model, released Ca2+ binds to negatively charged sites on the myoplasmic face of the voltage sensor and increases the local transmembrane potential, thus driving additional charge movement (the hump). This model successfully predicts the anomalous voltage dependence and all the kinetic properties of I gamma described in the previous papers. It also accounts for the inward phase in total asymmetric current and in the current suppressed by protocol 1. According to this model, I gamma accompanies activating transitions at the same set of voltage sensors as I beta. Therefore it should open additional release channels, which in turn should cause more I gamma, providing a positive feedback mechanism in the regulation of calcium release. PMID:1650812

Chitosan nanoparticles for the linear release of model cationic Peptide.

PubMed

Piras, Anna Maria; Sandreschi, Stefania; Maisetta, Giuseppantonio; Esin, Semih; Batoni, Giovanna; Chiellini, Federica

2015-07-01

The present study is focused on the development of a model drug delivery system (DDS) based on Chitosan (CS) nanoparticles using Renin substrate I (RSI) as model agent. RSI shares the main chemical-physical features of several biologically active antimicrobial peptides (AMPs). AMPs have a great therapeutic potential that is hampered by their lability in the biological fluids and as such they are perfect candidates for DDS. The development studies of quality DDS loaded with AMPs would require highly sensitive and specific quantification assays. The use of RSI allowed for the fine-tuning and optimization of the formulation parameters to promote the hydrophobic interactions between CS and the cationic peptide, favour the loading of the active ingredient and enhance the release properties of the carrier. RSI was encapsulated in chitosan NPs by mean of ionic gelation and a chromogenic enzymatic essay was carried out for the release kinetics evaluation. The developed formulations displayed almost 100% of encapsulation efficacy, low burst percentages, and a linear release of the model peptide. A release model was created showing a direct dependence on both the amount of RSI and NPs radius. Although CS has always been formulated with negatively charged active agents (e.g. oligonucleotides or anionic proteins), the use of ionotropic gelation in presence of a small cationic active agent promoted the formation of "core-shell" NPs. The described model, with tuneable linear release rates, appears eligible for further exploitation such as the loading of therapeutically active AMPs.

Electrically atomised formulations of timolol maleate for direct and on-demand ocular lens coatings.

PubMed

Mehta, Prina; Al-Kinani, Ali A; Haj-Ahmad, Rita; Arshad, Muhammad Sohail; Chang, Ming-Wei; Alany, Raid G; Ahmad, Zeeshan

2017-10-01

Advances in nanotechnology have enabled solutions for challenging drug delivery targets. While the eye presents numerous emerging opportunities for delivery, analysis and sensing; issues persist for conventional applications. This includes liquid phase formulation localisation on the ocular surface once administered as formulated eye-drops; with the vast majority of dosage (>90%) escaping from the administered site due to tear production and various drainage mechanisms. The work presented here demonstrates a single needle electrohydrodynamic (EHD) engineering process to nano-coat (as an on demand and controllable fiber depositing method) the surface of multiple contact lenses rendering formulations to be stationary on the lens and at the bio-interface. The coating process was operational based on ejected droplet charge and glaucoma drug timolol maleate (TM) was used to demonstrate surface coating optimisation, bio-surface permeation properties (flux, using a bovine model) and various kinetic models thereafter. Polymers PVP, PNIPAM and PVP:PNIPAM (50:50%w/w) were used to encapsulate the active. Nano-fibrous and particulate samples were characterised using SEM, FTIR, DSC and TGA to confirm structural and thermal stability of surface coated formulations. More than 52% of nano-structured coatings (for all formulations) were <200nm in diameter. In vitro studies show coatings to exhibit biphasic release profiles; an initial burst release followed by sustained release; with TM-loaded PNIPAM coating releasing most drug after 24h (89.8%). Kinetic modelling (Higuchi, Korsmeyer-Peppas) was indicative of quasi-Fickian diffusion whilst biological evaluation demonstrates adequate ocular tolerability. Results from permeation studies indicate coated lenses are ideal to reduce dosing regimen, which in turn will reduce systemic drug absorption. Florescent microscopy demonstrated probe and probe embedded coating behaviour from lens surface in vitro. The multiple lens surface coating method demonstrates sustained drug release yielding promising results; suggesting both novel device and method to enhance drug activity at the eyes surface which will reduce formulation drainage. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

Progesterone binding nano-carriers based on hydrophobically modified hyperbranched polyglycerols

NASA Astrophysics Data System (ADS)

Alizadeh Noghani, M.; Brooks, D. E.

2016-02-01

Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The results provide evidence to justify more detailed studies of interactions with biological systems, both single cells and in animal models.Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The results provide evidence to justify more detailed studies of interactions with biological systems, both single cells and in animal models. Electronic supplementary information (ESI) available: Fig. S-1: chemical structure of progesterone (Pro). Fig. S-2: 1H NMR spectrum of HPG-C8-MPEG. Fig. S-3: GPC chromatogram of HPG-C8-MPEG. Fig. S-4: 1H NMR spectrum of HPG-C12-MPEG. Fig. S-5: GPC chromatogram of HPG-C8-MPEG. Fig. S-6: FTIR spectrum of HPG-C8-MPEG. Fig. S-7: inverse-gated 13C NMR spectrum of HPG-C8-MPEG in methanol-d4. Fig. S-8: semi-log plot to determine initial rapid release kinetics for HPG-C8-MPEG/Pro in PBS. Fig. S-9: semi-log plot to determine secondary slow release kinetics for HPG-C8-MPEG/Pro in PBS. Fig. S-10: semi-log plot illustrating the kinetics of Pro release from HPG-C8-MPEG/Pro in plasma. Fig. S-11: dependence of k1 and Vp - Va. Fig. S-12: correlation between the maximum binding capacity of HPG-Cn-MPEG polymeric systems for binding Pro and their total mass of alkyl carbon external to the oxygen (R2 = 0.77 and p < 0.025). Table S-1: effect of loaded Pro on HPG-Cn-MPEG size. Fig. S-13. DLS size determination of HPG-C10-MPEG at 2 mg ml-1 (on the left) and HPG-C10-MPEG/Pro at 2 mg ml-1 of polymer and 25 μg ml-1 of Pro (on the right). The minor population of larger particles was reduced in diameter by Pro binding, illustrated above, consistent with an earlier report.11 See DOI: 10.1039/c5nr08175k

Long-term Controlled Drug Release from bi-component Electrospun Fibers

NASA Astrophysics Data System (ADS)

Xu, Shanshan; Zhang, Zixin; Xia, Qinghua; Han, Charles

Multi-drug delivery systems with timed programmed release are hard to be produced due to the complex drug release kinetics which mainly refers to the diffusion of drug molecules from the fiber and the degradation of the carrier. This study focused on the whole life-time story of the long-term drug releasing fibrous systems. Electrospun membrane utilizing FDA approved polymers and broad-spectrum antibiotics showed specific drug release profiles which could be divided into three stages based on the profile slope. With throughout morphology observation, cumulative release amount and releasing duration, releasing kinetics and critical factors were fully discussed during three stages. Through changing the second component, approximately linear drug release profile and a drug release duration about 13 days was prepared, which is perfect for preventing post-operative infection. The addition of this semi-crystalline polymer in turn influenced the fiber swelling and created drug diffusion channels. In conclusion, through adjusting and optimization of the blending component, initial burst release, delayed release for certain duration, and especially the sustained release profile could all be controlled, as well as specific anti-bacterial behavior could be obtained.

Nanostructured ultra-thin patches for ultrasound-modulated delivery of anti-restenotic drug

PubMed Central

Vannozzi, Lorenzo; Ricotti, Leonardo; Filippeschi, Carlo; Sartini, Stefania; Coviello, Vito; Piazza, Vincenzo; Pingue, Pasqualantonio; La Motta, Concettina; Dario, Paolo; Menciassi, Arianna

2016-01-01

This work aims to demonstrate the possibility to fabricate ultra-thin polymeric films loaded with an anti-restenotic drug and capable of tunable drug release kinetics for the local treatment of restenosis. Vascular nanopatches are composed of a poly(lactic acid) supporting membrane (thickness: ~250 nm) on which 20 polyelectrolyte bilayers (overall thickness: ~70 nm) are alternatively deposited. The anti-restenotic drug is embedded in the middle of the polyelectrolyte structure, and released by diffusion mechanisms. Nanofilm fabrication procedure and detailed morphological characterization are reported here. Barium titanate nanoparticles (showing piezoelectric properties) are included in the polymeric support and their role is investigated in terms of influence on nanofilm morphology, drug release kinetics, and cell response. Results show an efficient drug release from the polyelectrolyte structure in phosphate-buffered saline, and a clear antiproliferative effect on human smooth muscle cells, which are responsible for restenosis. In addition, preliminary evidences of ultrasound-mediated modulation of drug release kinetics are reported, thus evaluating the influence of barium titanate nanoparticles on the release mechanism. Such data were integrated with quantitative piezoelectric and thermal measurements. These results open new avenues for a fine control of local therapies based on smart responsive materials. PMID:26730191

Application of Physiologically Based Absorption Modeling to Characterize the Pharmacokinetic Profiles of Oral Extended Release Methylphenidate Products in Adults

PubMed Central

Yang, Xiaoxia; Duan, John; Fisher, Jeffrey

2016-01-01

A previously presented physiologically-based pharmacokinetic model for immediate release (IR) methylphenidate (MPH) was extended to characterize the pharmacokinetic behaviors of oral extended release (ER) MPH formulations in adults for the first time. Information on the anatomy and physiology of the gastrointestinal (GI) tract, together with the biopharmaceutical properties of MPH, was integrated into the original model, with model parameters representing hepatic metabolism and intestinal non-specific loss recalibrated against in vitro and in vivo kinetic data sets with IR MPH. A Weibull function was implemented to describe the dissolution of different ER formulations. A variety of mathematical functions can be utilized to account for the engineered release/dissolution technologies to achieve better model performance. The physiological absorption model tracked well the plasma concentration profiles in adults receiving a multilayer-release MPH formulation or Metadate CD, while some degree of discrepancy was observed between predicted and observed plasma concentration profiles for Ritalin LA and Medikinet Retard. A local sensitivity analysis demonstrated that model parameters associated with the GI tract significantly influenced model predicted plasma MPH concentrations, albeit to varying degrees, suggesting the importance of better understanding the GI tract physiology, along with the intestinal non-specific loss of MPH. The model provides a quantitative tool to predict the biphasic plasma time course data for ER MPH, helping elucidate factors responsible for the diverse plasma MPH concentration profiles following oral dosing of different ER formulations. PMID:27723791

Establishing Structure Property Relationship in Drug Partitioning into and Release from Niosomes: Physical Chemistry Insights with Anti-Inflammatory Drugs.

PubMed

Dasgupta, Moumita; Kishore, Nand

2017-09-28

Understanding the physical chemistry underlying interactions of drugs with delivery formulations is extremely important in devising effective drug delivery systems. The partitioning and release kinetics of diclofenac sodium and naproxen from Brij 30 and Triton X-100 niosomal formulations have been addressed based on structural characterization, partitioning energetics, and release kinetics, thus establishing a relationship between structures and observed properties. Both the drugs partition in nonpolar regions of TX-100 niosomes via stacking of aromatic rings. The combined effects of interactions of the drugs with polar head groups and the rigidity of the niosome vesicles determine entry and partitioning of drugs into niosomes. The observed slower rate of release of the drugs from the drug encapsulated niosomes of TX-100 than those of Brij 30, suggest stable complexation of drugs in the nonpolar interior of the former. No release of drugs from the niosomes was observed until 24 h even upon varying pH conditions without SDS. However, SDS in drug loaded niosomes led to release of drugs in as early as 6 h. The sustained pattern of in vitro release kinetics of the drugs thus observed from our niosomal preparations suggest these vesicular systems to be promising for pharamaceutical applications as potential drug delivery vehicles.

Effect of particle size of calcium phosphate based bioceramic drug delivery carrier on the release kinetics of ciprofloxacin hydrochloride: an in vitro study

NASA Astrophysics Data System (ADS)

Sasikumar, Swamiappan

2013-09-01

Hydroxyapatite (HAP) is the constituent of calcium phosphate based bone cement and it is extensively used as a bone substitute and drug delivery vehicle in various biomedical applications. In the present study we investigated the release kinetics of ciprofloxacin loaded HAP and analyzed its ability to function as a targeted and sustained release drug carrier. Synthesis of HAP was carried out by combustion method using tartaric acid as a fuel and nitric acid as an oxidizer. Powder XRD and FTIR techniques were employed to characterize the phase purity of the drug carrier and to verify the chemical interaction between the drug and carrier. The synthesized powders were sieve separated to make two different drug carriers with different particle sizes and the surface topography of the pellets of the drug carrier was imaged by AFM. Surface area and porosity of the drug carrier was carried out using surface area analyzer. The in-vitro drug release kinetics was performed in simulated body fluid, at 37.3°C. The amount of ciprofloxacin released is measured using UV-visible spectroscopy following the characteristic λ max of 278 nm. The release saturates around 450 h which indicates that it can be used as a targeted and sustained release carrier for bone infections.

Kinetic characterization of a novel endo-β-N-acetylglucosaminidase on concentrated bovine colostrum whey to release bioactive glycans.

PubMed

Karav, Sercan; Parc, Annabelle Le; de Moura Bell, Juliana Maria Leite Nobrega; Rouquié, Camille; Mills, David A; Barile, Daniela; Block, David E

2015-09-01

EndoBI-1 is a recently isolated endo-β-N-acetylglucosaminidase, which cleaves the N-N'-diacetyl chitobiose moiety found in the N-glycan core of high mannose, hybrid and complex N-glycans. These N-glycans have selective prebiotic activity for a key infant gut microbe, Bifidobacterium longum subsp. infantis. The broad specificity of EndoBI-1 suggests the enzyme may be useful for many applications, particularly for deglycosylating milk glycoproteins in dairy processing. To facilitate its commercial use, we determined kinetic parameters for EndoBI-1 on the model substrates ribonuclease B and bovine lactoferrin, as well as on concentrated bovine colostrum whey. Km values ranging from 0.25 to 0.49, 0.43 to 1.00 and 0.90 to 3.18 mg/mL and Vmax values ranging from 3.5×10(-3) to 5.09×10(-3), 4.5×10(-3) to 7.75×10(-3) and 1.9×10(-2)to 5.2×10(-2) mg/mL×min were determined for ribonuclease B, lactoferrin and whey, respectively. In general, EndoBI-1 showed the highest apparent affinity for ribonuclease B, while the maximum reaction rate was the highest for concentrated whey. EndoBI-1-released N-glycans were quantified by a phenol-sulphuric total carbohydrate assay and the resultant N-glycan structures monitored by nano-LC-Chip-Q-TOF MS. The kinetic parameters and structural characterization of glycans released suggest EndoBI-1 can facilitate large-scale release of complex, bioactive glycans from a variety of glycoprotein substrates. Moreover, these results suggest that whey, often considered as a waste product, can be used effectively as a source of prebiotic N-glycans. Copyright © 2015. Published by Elsevier Inc.

Desorption kinetics of ciprofloxacin in municipal biosolids determined by diffusion gradient in thin films.

PubMed

D'Angelo, E; Starnes, D

2016-12-01

Ciprofloxacin (CIP) is a commonly-prescribed antibiotic that is largely excreted by the body, and is often found at elevated concentrations in treated sewage sludge (biosolids) at municipal wastewater treatment plants. When biosolids are applied to soils, they could release CIP to surface runoff, which could adversely affect growth of aquatic organisms that inhabit receiving water bodies. The hazard risk largely depends on the amount of antibiotic in the solid phase that can be released to solution (labile CIP), its diffusion coefficient, and sorption/desorption exchange rates in biosolids particles. In this study, these processes were evaluated in a Class A Exceptional Quality Biosolids using a diffusion gradient in thin films (DGT) sampler that continuously removed CIP from solution, which induced desorption and diffusion in biosolids. Mass accumulation of antibiotic in the sampler over time was fit by a diffusion transport and exchange model available in the software tool 2D-DIFS to derive the distribution coefficient of labile CIP (K dl ) and sorption/desorption rate constants in the biosolids. The K dl was 13 mL g -1 , which equated to 16% of total CIP in the labile pool. Although the proportion of labile CIP was considerable, release rates to solution were constrained by slow desorption kinetics (desorption rate constant = 4 × 10 -6 s -1 ) and diffusion rate (effective diffusion coefficient = 6 × 10 -9  cm 2  s -1 . Studies are needed to investigate how changes in temperature, water content, pH and other physical and chemical characteristics can influence antibiotic release kinetics and availability and mobility in biosolid-amended soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nitric oxide-releasing chitosan film for enhanced antibacterial and in vivo wound-healing efficacy.

PubMed

Kim, Jong Oh; Noh, Jin-Ki; Thapa, Raj Kumar; Hasan, Nurhasni; Choi, Moonjeong; Kim, Jeong Hwan; Lee, Joon-Hee; Ku, Sae Kwang; Yoo, Jin-Wook

2015-08-01

Nitric oxide (NO) is a promising therapeutic agent with antibacterial and wound-healing properties. However, the gaseous state and short half-life of NO necessitate a formulation that can control its storage and release. In this study, we developed NO-releasing films (CS/NO film) composed of chitosan (CS) and S-nitrosoglutathione (GSNO) as a NO donor. Thermal analysis demonstrated molecular dispersion of GSNO in the films. In vitro release study revealed that NO release from CS/NO films followed Korsmeyer-Peppas model with Fickian diffusion kinetics. Moreover, the CS/NO film showed a stronger antibacterial activity against Pseudomonas aeruginosa (Gram-negative) and Staphylococcus aureus (Gram-positive) than the CS film. Further, the CS/NO film accelerated wound healing and epithelialization in a rat model of full-thickness wounds as compared to the CS film. Histopathological studies revealed that CS/NO films favorably enhanced the re-epithelialization and reconstruction of wounded skin. Therefore, our results suggest that CS/NO films could be a suitable formulation for treating full-thickness wounds. Copyright © 2015 Elsevier B.V. All rights reserved.

Encapsulation of anticancer drug copper bis(8-hydroxyquinoline) in hydroxyapatite for pH-sensitive targeted delivery and slow release.

PubMed

Weerasuriya, D R K; Wijesinghe, W P S L; Rajapakse, R M G

2017-02-01

There is a conspicuous progress in increasing anticancer drug delivery through the utilization of nanoparticles (NPs) as drug delivery agents. Hydroxyapatite (HA) gives improved clinical effectiveness of drugs by reducing systemic toxicity and broadening the spectrum of drug delivery since it is biocompatible and it can be targeted towards tumor cells. Herein, investigation of the potential of enhancing controlled drug release of the template model drug, copper bis-(8-hydroxyquinoline), by encapsulating it in hollow hydroxyapatite nano-carriers, is presented. Hydroxyapatite nanoparticles are synthesized by following four different routes to optimize its efficacy of drug loading. Copper bis-(8-hydroxyquinoline) is encapsulated by Method (a) which was effected by stirring the model drug and porous HA NPs in colloidal solution and Method (b) which was done during synthesis of hydroxyapatite nanoparticles in a solution of the model drug. In synthesizing nanoporous HA NPs, calcium carbonate is used as a template to create voids in HA. In each method, Ca/P ratio was ensured to be kept at 1.67:1. Appealing results are reported for the encapsulated product which was prepared by Method (a2). Method (a) was done at three different molar ratios of PO 4 3- :CO 3 2- and best result was obtained for that utilized 2.003:1 molar ratio (Method (a2).). It produced 98.67% of encapsulation efficiency and 2.9522mg/g of drug loading capacity. Release kinetics was studied at a range of pH values; the lower the pH of the medium the higher is the drug release. For instance, when considering the product which exhibited high encapsulation efficiency and high drug loading capacity, at pH3.5 during the first 8h it elicited about 13% of release, at pH5.0 about 8% release while at pH6.0 it was just 2.5%. During the 24-hour span, pH3.5 exhibited about 23.8%, at pH5.0 approximately 9% with an increasing trend of release and at pH6.0 showed a value just above 2.5%. As such, acidity of the cancerous cells can be made use to increase the drug slow-release kinetics at the vicinity of the cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Optimized in vivo detection of dopamine release using 18F-fallypride PET.

PubMed

Ceccarini, Jenny; Vrieze, Elske; Koole, Michel; Muylle, Tom; Bormans, Guy; Claes, Stephan; Van Laere, Koen

2012-10-01

The high-affinity D(2/3) PET radioligand (18)F-fallypride offers the possibility of measuring both striatal and extrastriatal dopamine release during activation paradigms. When a single (18)F-fallypride scanning protocol is used, task timing is critical to the ability to explore both striatal and extrastriatal dopamine release simultaneously. We evaluated the sensitivity and optimal timing of task administration for a single (18)F-fallypride PET protocol and the linearized simplified reference region kinetic model in detecting both striatal and extrastriatal reward-induced dopamine release, using human and simulation studies. Ten healthy volunteers underwent a single-bolus (18)F-fallypride PET protocol. A reward responsiveness learning task was initiated at 100 min after injection. PET data were analyzed using the linearized simplified reference region model, which accounts for time-dependent changes in (18)F-fallypride displacement. Voxel-based statistical maps, reflecting task-induced D(2/3) ligand displacement, and volume-of-interest-based analysis were performed to localize areas with increased ligand displacement after task initiation, thought to be proportional to changes in endogenous dopamine release (γ parameter). Simulated time-activity curves for baseline and hypothetical dopamine release functions (different peak heights of dopamine and task timings) were generated using the enhanced receptor-binding kinetic model to investigate γ as a function of these parameters. The reward task induced increased ligand displacement in extrastriatal regions of the reward circuit, including the medial orbitofrontal cortex, ventromedial prefrontal cortex, and dorsal anterior cingulate cortex. For task timing of 100 min, ligand displacement was found for the striatum only when peak height of dopamine was greater than 240 nM, whereas for frontal regions, γ was always positive for all task timings and peak heights of dopamine. Simulation results for a peak height of dopamine of 200 nM showed that an effect of striatal ligand displacement could be detected only when task timing was greater than 120 min. The prefrontal and anterior cingulate cortices are involved in reward responsiveness that can be measured using (18)F-fallypride PET in a single scanning session. To measure both striatal and extrastriatal dopamine release, the height of dopamine released and task timing need to be considered in designing activation studies depending on regional D(2/3) density.

Time-Temperature Indicator Based on Enzymatic Degradation of Dye-Loaded Polyhydroxybutyrate.

PubMed

Anbukarasu, Preetam; Sauvageau, Dominic; Elias, Anastasia L

2017-09-01

An enzyme activated time-temperature indicator (TTI) which produces a direct colour change concomitant to variations in integrated time and temperature conditions is described. This direct colour change is realised by degrading a dye-loaded polyhydroxybutyrate (PHB) film by a depolymerase enzyme. The degradation of the PHB film by the enzyme causes the release of the dye in solution, which in turn undergoes an optical transition from clear to coloured with elapsing time. Macroscopic and microscopic optical observations confirms the uniform distribution of the dye in the PHB film. The dye release kinetics, mediated by the enzymatic reaction, are tested at different temperatures ranging from 4 to 37 °C, and are used to determine the suitability of a dye-loaded PHB as a time-temperature indicator for fresh food products based on kinetic parameters previously reported. The kinetic analysis shows that the activation energy of the dye release process is 74 kJ mol -1 , and that, at 37 °C, the dye would be totally released within 6 h. However, when incubated at 4 °C, the TTI requires in the range of 168 h (7 days) to release all the dye. These kinetics values highlight the potential of the TTI for monitoring fresh food products that have optimum shelf life around 4 °C. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Formation of polymeric toroidal-spiral particles.

PubMed

Sharma, Vishal; Szymusiak, Magdalena; Shen, Hao; Nitsche, Ludwig C; Liu, Ying

2012-01-10

Compared to spherical matrices, particles with well-defined internal structure provide large surface to volume ratio and predictable release kinetics for the encapsulated payloads. We describe self-assembly of polymeric particles, whereby competitive kinetics of viscous sedimentation, diffusion, and cross-linking yield a controllable toroidal-spiral (T-S) structure. Precursor polymeric droplets are splashed through the surface of a less dense, miscible solution, after which viscous forces entrain the surrounding bulk solution into the sedimenting polymer drop to form T-S channels. The intricate structure forms because low interfacial tension between the two miscible solutions is dominated by viscous forces. The biocompatible polymer, poly(ethylene glycol) diacrylate (PEG-DA), is used to demonstrate the solidification of the T-S shapes at various configurational stages by UV-triggered cross-linking. The dimensions of the channels are controlled by Weber number during impact on the surface, and Reynolds number and viscosity ratio during subsequent sedimentation. We anticipate applications of the T-S particle in drug delivery, wherein diffusion through these T-S channels and the polymer matrix would offer parallel release pathways for molecules of different sizes. Polyphosphate, as a model macromolecule, is entrained in T-S particles during their formation. The in vitro release kinetics of polyphosphate from the T-S particles with various channel length and width is reported. In addition, self-assembly of T-S particles occurs in a single step under benign conditions for delicate macromolecules, and appears conducive to scaleup.

Tycho 2: A Proxy Application for Kinetic Transport Sweeps

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

Garrett, Charles Kristopher; Warsa, James S.

2016-09-14

Tycho 2 is a proxy application that implements discrete ordinates (SN) kinetic transport sweeps on unstructured, 3D, tetrahedral meshes. It has been designed to be small and require minimal dependencies to make collaboration and experimentation as easy as possible. Tycho 2 has been released as open source software. The software is currently in a beta release with plans for a stable release (version 1.0) before the end of the year. The code is parallelized via MPI across spatial cells and OpenMP across angles. Currently, several parallelization algorithms are implemented.

Pinosylvin-Based Polymers: Biodegradable Poly(Anhydride-Esters) for Extended Release of Antibacterial Pinosylvin.

PubMed

Bien-Aime, Stephan; Yu, Weiling; Uhrich, Kathryn E

2016-07-01

Pinosylvin is a natural stilbenoid known to exhibit antibacterial bioactivity against foodborne bacteria. In this work, pinosylvin is chemically incorporated into a poly(anhydride-ester) (PAE) backbone via melt-condensation polymerization, and characterized with respect to its physicochemical and thermal properties. In vitro release studies demonstrate that pinosylvin-based PAEs hydrolytically degrade over 40 d to release pinosylvin. Pseudo-first order kinetic experiments on model compounds, butyric anhydride and 3-butylstilbene ester, indicate that the anhydride linkages hydrolyze first, followed by the ester bonds to ultimately release pinosylvin. An antibacterial assay shows that the released pinosylvin exhibit bioactivity, while in vitro cytocompatibility studies demonstrate that the polymer is noncytotoxic toward fibroblasts. These preliminary findings suggest that the pinosylvin-based PAEs can serve as food preservatives in food packaging materials by safely providing antibacterial bioactivity over extended time periods. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Enhanced gastric retention and drug release via development of novel floating microspheres based on Eudragit E100 and polycaprolactone: synthesis and in vitro evaluation

PubMed Central

Farooq, Umar; Khan, Samiullah; Nawaz, Shahid; Ranjha, Nazar Mohammad; Haider, Malik Salman; Khan, Muhammad Muzamil; Dar, Eshwa; Nawaz, Ahmad

2017-01-01

Abstract Eudragit E 100 and polycaprolactone (PCL) floating microspheres for enhanced gastric retention and drug release were successfully prepared by oil in water solvent evaporation method. Metronidazole benzoate, an anti-protozoal drug, was used as a model drug. Polyvinyl alcohol was used as an emulsifier. The prepared microspheres were observed for % recovery, % degree of hydration, % water uptake, % drug loading, % buoyancy and % drug release. The physico-chemical properties of the microspheres were studied by calculating encapsulation efficiency of microspheres and drug release kinetics. Drug release characteristics of microspheres were studied in simulated gastric fluid and simulated intestinal fluid i.e., at pH 1.2 and 7.4 respectively. Fourier transform infrared spectroscopy was used to reveal the chemical interaction between drug and polymers. Scanning electron microscopy was conducted to study the morphology of the synthesized microspheres. PMID:29491813

High-pressure processing of apple juice: kinetics of pectin methyl esterase inactivation.

PubMed

Riahi, Esmaeil; Ramaswamy, Hosahalli S

2003-01-01

High-pressure (HP) inactivation kinetics of pectin methyl esterase (PME) in apple juice were evaluated. Commercial PME was dispensed in clarified apple juice, sealed in dual peel sterilizable plastic bags, and subjected to different high-pressure processing conditions (200-400 MPa, 0-180 min). Residual enzyme activity was determined by a titration method estimating the rate of free carboxyl group released by the enzyme acting on pectin substrate at pH 7.5 (30 degrees C). The effects of pressure level and pressure holding time on enzyme inactivation were significant (p < 0.05). PME from the microbial source was found to be more resistant (p < 0.05) to pressure inactivation than PME from the orange peel. Almost a full decimal reduction in the activity of commercial PME was achieved by HP treatment at 400 MPa for 25 min. Inactivation kinetics were evaluated on the basis of a dual effect model involving a pressure pulse effect and a first-order rate model, and the pressure sensitivity of rate constants was modeled by using the z-value concept.

The Disintegration Process in Microcrystalline Cellulose Based Tablets, Part 1: Influence of Temperature, Porosity and Superdisintegrants.

PubMed

Yassin, Samy; Goodwin, Daniel J; Anderson, Andrew; Sibik, Juraj; Wilson, D Ian; Gladden, Lynn F; Zeitler, J Axel

2015-10-01

Disintegration performance was measured by analysing both water ingress and tablet swelling of pure microcrystalline cellulose (MCC) and in mixture with croscarmellose sodium using terahertz pulsed imaging (TPI). Tablets made from pure MCC with porosities of 10% and 15% showed similar swelling and transport kinetics: within the first 15 s, tablets had swollen by up to 33% of their original thickness and water had fully penetrated the tablet following Darcy flow kinetics. In contrast, MCC tablets with a porosity of 5% exhibited much slower transport kinetics, with swelling to only 17% of their original thickness and full water penetration reached after 100 s, dominated by case II transport kinetics. The effect of adding superdisintegrant to the formulation and varying the temperature of the dissolution medium between 20°C and 37°C on the swelling and transport process was quantified. We have demonstrated that TPI can be used to non-invasively analyse the complex disintegration kinetics of formulations that take place on timescales of seconds and is a promising tool to better understand the effect of dosage form microstructure on its performance. By relating immediate-release formulations to mathematical models used to describe controlled release formulations, it becomes possible to use this data for formulation design. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3440-3450, 2015. © 2015 The Authors. Journal of Pharmaceutical Sciences published by Wiley Periodicals, Inc. and the American Pharmacists Association.

Controlled nerve growth factor release from multi-ply alginate/chitosan-based nerve conduits.

PubMed

Pfister, Lukas A; Alther, Eva; Papaloïzos, Michaël; Merkle, Hans P; Gander, Bruno

2008-06-01

The delivery kinetics of growth factors has been suggested to play an important role in the regeneration of peripheral nerves following axotomy. In this context, we designed a nerve conduit (NC) with adjustable release kinetics of nerve growth factor (NGF). A multi-ply system was designed where NC consisting of a polyelectrolyte alginate/chitosan complex was coated with layers of poly(lactide-co-glycolide) (PLGA) to control the release of embedded NGF. Prior to assessing the in vitro NGF release from NC, various release test media, with and without stabilizers for NGF, were evaluated to ensure adequate quantification of NGF by ELISA. Citrate (pH 5.0) and acetate (pH 5.5) buffered saline solutions containing 0.05% Tween 20 yielded the most reliable results for ELISA active NGF. The in vitro release experiments revealed that the best results in terms of reproducibility and release control were achieved when the NGF was embedded between two PLGA layers and the ends of the NC tightly sealed by the PLGA coatings. The release kinetics could be efficiently adjusted by accommodating NGF at different radial locations within the NC. A sustained release of bioactive NGF in the low nanogram per day range was obtained for at least 15days. In conclusion, the developed multi-ply NGF loaded NC is considered a suitable candidate for future implantation studies to gain insight into the relationship between local growth factor availability and nerve regeneration.

Impact of IGF-I release kinetics on bone healing: a preliminary study in sheep.

PubMed

Luginbuehl, Vera; Zoidis, Evangelos; Meinel, Lorenz; von Rechenberg, Brigitte; Gander, Bruno; Merkle, Hans P

2013-09-01

Spatiotemporal release of growth factors from a delivery device can profoundly affect the efficacy of bone growth induction. Here, we report on a delivery platform based on the encapsulation of insulin-like growth factor I (IGF-I) in different poly(D,L-lactide) (PLA) and poly(D,L-lactide-co-glycolide) (PLGA) microsphere (MS) formulations to control IGF-I release kinetics. In vitro IGF-I release profiles generally exhibited an initial burst (14-36% of total IGF-I content), which was followed by a more or less pronounced dormant phase with little release (2 to 34 days), and finally, a third phase of re-increased IGF-I release. The osteoinductive potential of these different IGF-I PL(G)A MS formulations was tested in studies using 8-mm metaphyseal drill hole bone defects in sheep. Histomorphometric analysis at 3 and 6 weeks after surgery showed that new bone formation was improved in the defects locally treated with IGF-I PL(G)A MS (n=5) as compared to defects filled with IGF-I-free PL(G)A MS (n=4). The extent of new bone formation was affected by the particular release kinetics, although a definitive relationship was not evident. Local administration of IGF-I resulted in down-regulation of inflammatory marker genes in all IGF-I treated defects. The over-expression of growth factor genes in response to IGF-I delivery was restricted to formulations that produced osteogenic responses. These experiments demonstrate the osteoinductive potential of sustained IGF-I delivery and show the importance of delivery kinetics for successful IGF-I-based therapies. Copyright © 2013 Elsevier B.V. All rights reserved.

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

Lombardo, N.J.; Marseille, T.J.; White, M.D.

TRUMP-BD (Boil Down) is an extension of the TRUMP (Edwards 1972) computer program for the analysis of nuclear fuel assemblies under severe accident conditions. This extension allows prediction of the heat transfer rates, metal-water oxidation rates, fission product release rates, steam generation and consumption rates, and temperature distributions for nuclear fuel assemblies under core uncovery conditions. The heat transfer processes include conduction in solid structures, convection across fluid-solid boundaries, and radiation between interacting surfaces. Metal-water reaction kinetics are modeled with empirical relationships to predict the oxidation rates of steam-exposed Zircaloy and uranium metal. The metal-water oxidation models are parabolic inmore » form with an Arrhenius temperature dependence. Uranium oxidation begins when fuel cladding failure occurs; Zircaloy oxidation occurs continuously at temperatures above 13000{degree}F when metal and steam are available. From the metal-water reactions, the hydrogen generation rate, total hydrogen release, and temporal and spatial distribution of oxide formations are computed. Consumption of steam from the oxidation reactions and the effect of hydrogen on the coolant properties is modeled for independent coolant flow channels. Fission product release from exposed uranium metal Zircaloy-clad fuel is modeled using empirical time and temperature relationships that consider the release to be subject to oxidation and volitization/diffusion ( bake-out'') release mechanisms. Release of the volatile species of iodine (I), tellurium (Te), cesium (Ce), ruthenium (Ru), strontium (Sr), zirconium (Zr), cerium (Cr), and barium (Ba) from uranium metal fuel may be modeled.« less

Reconnecting flux-rope dynamo.

PubMed

Baggaley, Andrew W; Barenghi, Carlo F; Shukurov, Anvar; Subramanian, Kandaswamy

2009-11-01

We develop a model of the fluctuation dynamo in which the magnetic field is confined to thin flux ropes advected by a multiscale model of turbulence. Magnetic dissipation occurs only via reconnection of the flux ropes. This model can be viewed as an implementation of the asymptotic limit R_{m}-->infinity for a continuous magnetic field, where magnetic dissipation is strongly localized to small regions of strong-field gradients. We investigate the kinetic-energy release into heat mediated by the dynamo action, both in our model and by solving the induction equation with the same flow. We find that a flux-rope dynamo is an order of magnitude more efficient at converting mechanical energy into heat. The probability density of the magnetic energy release in reconnections has a power-law form with the slope -3 , consistent with the solar corona heating by nanoflares.

Modulation of venlafaxine hydrochloride release from press coated matrix tablet.

PubMed

Gohel, M C; Soni, C D; Nagori, S A; Sarvaiya, K G

2008-01-01

The aim of present study was to prepare novel modified release press coated tablets of venlafaxine hydrochloride. Hydroxypropylmethylcellulose K4M and hydroxypropylmethylcellulose K100M were used as release modifier in core and coat, respectively. A 3(2) full factorial design was adopted in the optimization study. The drug to polymer ratio in core and coat were chosen as independent variables. The drug release in the first hour and drug release rate between 1 and 12 h were chosen as dependent variables. The tablets were characterized for dimension analysis, crushing strength, friability and in vitro drug release. A check point batch, containing 1:2.6 and 1:5.4 drug to polymer in core and coat respectively, was prepared. The tablets of check point batch were subjected to in vitro drug release in dissolution media with pH 5, 7.2 and distilled water. The kinetics of drug release was best explained by Korsmeyer and Peppas model (anomalous non-Fickian diffusion). The systematic formulation approach enabled us to develop modified release venlafaxine hydrochloride tablets.

Kinetics of zinc release from ground tire rubber and rubber ash in a calcareous soil as alternatives to Zn fertilizers

USDA-ARS?s Scientific Manuscript database

Ground rubber contains 15-20 g Zn/kg but very low levels of Cd and could serve as an inexpensive byproduct Zn fertilizer. The aim of this investigation was to test the kinetics of Zn release in a soil treated with ground tire rubber and rubber ash compared with commercial Zn fertilizer and a labora...

High-throughput screening of PLGA thin films utilizing hydrophobic fluorescent dyes for hydrophobic drug compounds.

PubMed

Steele, Terry W J; Huang, Charlotte L; Kumar, Saranya; Widjaja, Effendi; Chiang Boey, Freddy Yin; Loo, Joachim S C; Venkatraman, Subbu S

2011-10-01

Hydrophobic, antirestenotic drugs such as paclitaxel (PCTX) and rapamycin are often incorporated into thin film coatings for local delivery using implantable medical devices and polymers such as drug-eluting stents and balloons. Selecting the optimum coating formulation through screening the release profile of these drugs in thin films is time consuming and labor intensive. We describe here a high-throughput assay utilizing three model hydrophobic fluorescent compounds: fluorescein diacetate (FDAc), coumarin-6, and rhodamine 6G that were incorporated into poly(d,l-lactide-co-glycolide) (PLGA) and PLGA-polyethylene glycol films. Raman microscopy determined the hydrophobic fluorescent dye distribution within the PLGA thin films in comparison with that of PCTX. Their subsequent release was screened in a high-throughput assay and directly compared with HPLC quantification of PCTX release. It was observed that PCTX controlled-release kinetics could be mimicked by a hydrophobic dye that had similar octanol-water partition coefficient values and homogeneous dissolution in a PLGA matrix as the drug. In particular, FDAc was found to be the optimal hydrophobic dye at modeling the burst release as well as the total amount of PCTX released over a period of 30 days. Copyright © 2011 Wiley-Liss, Inc.

Modeling drug release from PVAc/PVP matrix tablets.

PubMed

Siepmann, F; Eckart, K; Maschke, A; Kolter, K; Siepmann, J

2010-01-25

Kollidon SR-based matrix tablets containing various amounts of diprophylline were prepared and thoroughly characterized in vitro. This includes drug release measurements in 0.1M HCl and phosphate buffer pH 7.4, monitoring of changes in the tablet's height and diameter, morphology as well as dry mass upon exposure to the release media. Based on these experimental results, a mechanistic realistic mathematical theory is proposed, taking into account the given initial and boundary conditions as well as radial and axial mass transport in cylinders. Importantly, good agreement between theory and experiment was obtained in all cases, indicating that drug diffusion with constant diffusivity is the dominant mass transport mechanism in these systems. Furthermore, the proposed theory was used to quantitatively predict the effects of the initial tablet height and diameter on the resulting drug release patterns. These theoretical predictions were compared with independently measured drug release kinetics. Good agreement was observed in all cases, proving the validity of the mathematical theory and illustrating the latter's practical benefit: The model can help to significantly facilitate the recipe optimization of this type of advanced drug delivery systems in order to achieve a desired release profile. Copyright 2009 Elsevier B.V. All rights reserved.

Hydrogen release from 800 MeV proton-irradiated tungsten

NASA Astrophysics Data System (ADS)

Oliver, B. M.; Venhaus, T. J.; Causey, R. A.; Garner, F. A.; Maloy, S. A.

2002-12-01

Tungsten irradiated in spallation neutron sources, such as those proposed for the accelerator production of tritium (APT) project, will contain large quantities of generated helium and hydrogen gas. Tungsten used in proposed fusion reactors will also be exposed to neutrons, and the generated protium will be accompanied by deuterium and tritium diffusing in from the plasma-facing surface. The release kinetics of these gases during various off-normal scenarios involving loss of coolant and after heat-induced rises in temperature are of particular interest for both applications. To determine the release kinetics of hydrogen from tungsten, tungsten rods irradiated with 800 MeV protons in the Los Alamos Neutron Science Center (LANSCE) to high exposures as part of the APT project have been examined. Hydrogen evolution from the tungsten has been measured using a dedicated mass-spectrometer system by subjecting the specimens to an essentially linear temperature ramp from ˜300 to ˜1500 K. Release profiles are compared with predictions obtained using the Tritium Migration Analysis Program (TMAP4). The measurements show that for high proton doses, the majority of the hydrogen is released gradually, starting at about 900 K and reaching a maximum at about 1400 K, where it drops fairly rapidly. Comparisons with TMAP show quite reasonable agreement using a trap energy of 1.4 eV and a trap density of ˜7%. There is a small additional release fraction occurring at ˜550 K, which is believed to be associated with low-energy trapping at or near the surface, and, therefore, was not included in the bulk TMAP model.

Quantitative diffusion and swelling kinetic measurements using large-angle interferometric refractometry.

PubMed

Saunders, John E; Chen, Hao; Brauer, Chris; Clayton, McGregor; Chen, Weijian; Barnes, Jack A; Loock, Hans-Peter

2015-12-07

The uptake and release of sorbates into films and coatings is typically accompanied by changes of the films' refractive index and thickness. We provide a comprehensive model to calculate the concentration of the sorbate from the average refractive index and the film thickness, and validate the model experimentally. The mass fraction of the analyte partitioned into a film is described quantitatively by the Lorentz-Lorenz equation and the Clausius-Mosotti equation. To validate the model, the uptake kinetics of water and other solvents into SU-8 films (d = 40-45 μm) were explored. Large-angle interferometric refractometry measurements can be used to characterize films that are between 15 μm to 150 μm thick and, Fourier analysis, is used to determine independently the thickness, the average refractive index and the refractive index at the film-substrate interface at one-second time intervals. From these values the mass fraction of water in SU-8 was calculated. The kinetics were best described by two independent uptake processes having different rates. Each process followed one-dimensional Fickian diffusion kinetics with diffusion coefficients for water into SU-8 photoresist film of 5.67 × 10(-9) cm(2) s(-1) and 61.2 × 10(-9) cm(2) s(-1).

Formulation development of physiological environment responsive periodontal drug delivery system for local delviery of metronidazole benzoate.

PubMed

Dabhi, Mahesh R; Sheth, Navin R

2013-03-01

The objective of the present investigation was to develop and evaluate physiological environment responsive periodontal drug delivery system (PERPDDS) for local delivery of metronidazole benzoate. Poly-ϵ-caprolactone an in situ precipitating polymer was used in combination with, carbopol 934P, a pH simulative polymer to develop PERPDDS. The prepared PERPDDS was evaluated for various parameters such as in vitro gelling capacity, viscosity, rheology, compatibility study, and in vitro diffusion study. A 3(2) full factorial design was used to investigate the influence of formulation variables. Drug release data from all formulations were fitted to different kinetic models and the korsemeyer-peppas model was found the best fit model. The value of diffusional exponent (n) was in between 0.3283 and 0.3979 indicating purely fickian diffusion release mechanism. Increasing the concentration of each polymeric component increases viscosity, and time for 50% and 90% drug release was observed and graphically represented by the surface response and contour plots.

An Approach to the Study of the Interactions between Ellagitannins and Oxygen during Oak Wood Aging.

PubMed

García-Estévez, Ignacio; Alcalde-Eon, Cristina; Martínez-Gil, Ana María; Rivas-Gonzalo, Julián C; Escribano-Bailón, M Teresa; Nevares, Ignacio; Del Alamo-Sanza, María

2017-08-09

During the aging of red wine in oak wood barrels, or in alternative aging systems, interactions between the compounds released from wood, the compounds of the wine, and oxygen can take place. The main objective of the present work was to study oxygen-ellagitannin interactions by monitoring their levels in three model systems, all containing the same amounts of French oak chips and differing only in the oxygen content: total absence, only the oxygen released from the chips, and air-saturated (model systems F, OW, and OS, respectively). This study has highlighted the influence of oxygen in the ellagitannins' evolution and the relevance of the oxygen trapped into the oak chips, reporting for the first time the kinetics of oxygen release to the model wine. Furthermore, the indirect contribution of oxygen to the ellagitannins' disappearance by boosting autoxidative reactions has also been pointed out. Vescalagin seems to be the ellagitannin most affected by the initial oxygen levels.

Ketorolac tromethamine floating beads for oral application: Characterization and in vitro/in vivo evaluation

PubMed Central

Abou el Ela, Amal El Sayeh F.; Hassan, Maha A.; El- Maraghy, Dalia A.

2013-01-01

The floating beads have been employed to make a sustained release of the drug in the stomach and to decrease the dose of the drug and hence overcome its side effects. The common benefits of the floating beads were it is easy preparation, without the need of a high temperature, and high percentage of the drug entrapment. In the present work, the Ketorolac tromethamine (KT) floating beads were prepared by extrusion congealing method utilizing calcium carbonate as a gas forming agent. The physical characters of the produced beads were investigated such as KT yield, KT loading, and entrapment efficiency of the drug. In addition, floating behavior, swelling, particle size, morphology and KT stability were also evaluated. In vitro drug release study was carried out, and the kinetics of the release was evaluated using the linear regression method. Furthermore, the in vivo analgesic effect of KT after oral administration of the selected formula of floating beads (F10) was carried out using hot plate and tail flick methods. Oral commercial KT tablets and KT solution were used for the comparison. The prepared beads remained floated for more than 8 h. The optimized formulation (F10) exhibited prolonged drug release (more than 8 h) and the drug release follows the Higuchi kinetic model, with a Fickian diffusion mechanism according to Korsmeyer-Peppas (n = 0.466). Moreover, F10 showed a sustained analgesic effect as compared to the commercial tablet. PMID:25161380

Indirect coupling of phosphate release to de novo tension generation during muscle contraction.

PubMed Central

Davis, J S; Rodgers, M E

1995-01-01

A key question in muscle contraction is how tension generation is coupled to the chemistry of the actomyosin ATPase. Biochemical and mechanochemical experiments link tension generation to a change in structure associated with phosphate release. Length-jump and temperature-jump experiments, on the other hand, implicate phase 2slow, a significantly faster, markedly strain-sensitive kinetic process in tension generation. We use a laser temperature jump to probe the kinetics and mechanism of tension generation in skinned rabbit psoas fibers--an appropriate method since both phosphate release and phase 2slow are readily perturbed by temperature. Kinetics characteristic of the structural change associated with phosphate release are observed only when phosphate is added to fibers. When present, it causes a reduction in fiber tension; otherwise, no force is generated when it is perturbed. We therefore exclude this step from tension generation. The kinetics of de novo tension generation by the temperature-jump equivalent of phase 2slow appear unaffected by phosphate binding. We therefore propose that phosphate release is indirectly coupled to de novo tension generation via a steady-state flux through an irreversible step. We conclude that tension generation occurs in the absence of chemical change as the result of an entropy-driven transition between strongly bound crossbridges in the actomyosin-ADP state. The mechanism resembles the operation of a clock, with phosphate release providing the energy to tension the spring, and the irreversible step functions as the escapement mechanism, which is followed in turn by tension generation as the movement of the hands. Images Fig. 6 PMID:7479824

The "trapped fraction" and interfacial jumps of concentration in fission products release from coated fuel particles

NASA Astrophysics Data System (ADS)

Ivanov, A. S.; Rusinkevich, A. A.; Taran, M. D.

2018-01-01

The FP Kinetics computer code [1] designed for calculation of fission products release from HTGR coated fuel particles was modified to allow consideration of chemical bonding, effects of limited solubility and component concentration jumps at interfaces between coating layers. Curves of Cs release from coated particles calculated with the FP Kinetics and PARFUME [2] codes were compared. It has been found that the consideration of concentration jumps at silicon carbide layer interfaces allows giving an explanation of some experimental data on Cs release obtained from post-irradiation heating tests. The need to perform experiments for measurement of solubility limits in coating materials was noted.

Coupling of exothermic and endothermic hydrogen storage materials

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

Brooks, Kriston P.; Bowden, Mark E.; Karkamkar, Abhijeet J.

2016-08-01

Chemical hydrogen storage (CHS) materials are a high-storage-density alternative to the gaseous compressed hydrogen currently used to provide hydrogen for fuel cell vehicles. One of the challenges of CHS materials is addressing the thermodynamic and kinetic barriers required to break the chemical bonds and release the hydrogen. Coupling CHS reactions that are endothermic and exothermic during the dehydrogenation can improve the system on-board energy efficiency and thermal control, making such materials viable. Acceptable coupling between reactions requires both thermodynamic and kinetics considerations. Models were developed to predict the reaction enthalpy and rate required to achieve high conversions for both reactionsmore » based on experimental measurements. These modeling results show that the efficiency of coupling of an exothermic and endothermic reaction is more sensitive the magnitude of the ratio of the exothermic and endothermic enthalpies than the ratio of the rates of the two steps. The modeling shows further that a slower rate of the endothermic step is desirable to permit sufficient heating of the reactor by the exothermic step. We look at two examples of a sequential and parallel reaction scheme and provide some of the first insight into the required temperature range to maximize the H2 release from 1,2-BN cyclohexane and indoline.« less

A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

PubMed Central

Guo, Jun; Ge, Jian-long; Hao, Mei; Sun, Zhi-cheng; Wu, Xin-sheng; Zhu, Jian-bing; Wang, Wei; Yao, Pan-tong; Lin, Wei; Xue, Lei

2015-01-01

Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP), and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles. PMID:25825223

Particle acceleration in a complex solar active region modelled by a Cellular automata model

NASA Astrophysics Data System (ADS)

Dauphin, C.; Vilmer, N.; Anastasiadis, A.

2004-12-01

The models of cellular automat allowed to reproduce successfully several statistical properties of the solar flares. We use a cellular automat model based on the concept of self-organised critical system to model the evolution of the magnetic energy released in an eruptive active area. Each burst of magnetic energy released is assimilated to a process of magnetic reconnection. We will thus generate several current layers (RCS) where the particles are accelerated by a direct electric field. We calculate the energy gain of the particles (ions and electrons) for various types of magnetic configuration. We calculate the distribution function of the kinetic energy of the particles after their interactions with a given number of RCS for each type of configurations. We show that the relative efficiency of the acceleration of the electrons and the ions depends on the selected configuration.

Analyzing and modeling the kinetics of amyloid beta pores associated with Alzheimer’s disease pathology

DOE PAGES

Ullah, Ghanim; Demuro, Angelo; Parker, Ian; ...

2015-09-08

Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca 2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca 2+) homeostasis. The resultant up-regulation of intracellular Ca 2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca 2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca 2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. Themore » fluorescence time-series data from individual pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca 2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca 2+ permeability transition into those with high open probability and Ca 2+ permeability.« less

In vitro dissolution kinetic study of theophylline from hydrophilic and hydrophobic matrices.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Abdulhalim, Abdulatif A

2006-01-01

Oral dosage forms containing 300 mg theophylline in matrix type tablets, were prepared by direct compression method using two kinds of matrices, glycerylbehenate (hydrophobic), and (hydroxypropyl)methyl cellulose (hydrophilic). The in vitro release kinetics of these formulations were studied at pH 6.8 using the USP dissolution apparatus with the paddle assemble. The kinetics of the dissolution process were studied by analyzing the dissolution data using four kinetic equations, the zero-order equation, the first-order equation, the Higuchi square root equation and the Hixson-Crowell cube root law. The analysis of the dissolution kinetic data for the theophylline preparations in this study shows that it follows the first order kinetics and the release process involves erosion / diffusion and an alteration in the surface area and diameter of the matrix system, as well as in the diffusion path length from the matrix drug load during the dissolution process. This relation is best described by the use of both the first-order equation and the Hixson-Crowell cube root law.

Modelling biological Cr(VI) reduction in aquifer microcosm column systems.

PubMed

Molokwane, Pulane E; Chirwa, Evans M N

2013-01-01

Several chrome processing facilities in South Africa release hexavalent chromium (Cr(VI)) into groundwater resources. Pump-and-treat remediation processes have been implemented at some of the sites but have not been successful in reducing contamination levels. The current study is aimed at developing an environmentally friendly, cost-effective and self-sustained biological method to curb the spread of chromium at the contaminated sites. An indigenous Cr(VI)-reducing mixed culture of bacteria was demonstrated to reduce high levels of Cr(VI) in laboratory samples. The effect of Cr(VI) on the removal rate was evaluated at concentrations up to 400 mg/L. Following the detailed evaluation of fundamental processes for biological Cr(VI) reduction, a predictive model for Cr(VI) breakthrough through aquifer microcosm reactors was developed. The reaction rate in batch followed non-competitive rate kinetics with a Cr(VI) inhibition threshold concentration of approximately 99 mg/L. This study evaluates the application of the kinetic parameters determined in the batch reactors to the continuous flow process. The model developed from advection-reaction rate kinetics in a porous media fitted best the effluent Cr(VI) concentration. The model was also used to elucidate the logistic nature of biomass growth in the reactor systems.

Reactive transport modelling of groundwater chemistry in a chalk aquifer at the watershed scale

NASA Astrophysics Data System (ADS)

Mangeret, A.; De Windt, L.; Crançon, P.

2012-09-01

This study investigates thermodynamics and kinetics of water-rock interactions in a carbonate aquifer at the watershed scale. A reactive transport model is applied to the unconfined chalk aquifer of the Champagne Mounts (France), by considering both the chalk matrix and the interconnected fracture network. Major element concentrations and main chemical parameters calculated in groundwater and their evolution along flow lines are in fair agreement with field data. A relative homogeneity of the aquifer baseline chemistry is rapidly reached in terms of pH, alkalinity and Ca concentration since calcite equilibrium is achieved over the first metres of the vadose zone. However, incongruent chalk dissolution slowly releases Ba, Mg and Sr in groundwater. Introducing dilution effect by rainwater infiltration and a local occurrence of dolomite improves the agreement between modelling and field data. The dissolution of illite and opal-CT, controlling K and SiO2 concentrations in the model, can be approximately tackled by classical kinetic rate laws, but not the incongruent chalk dissolution. An apparent kinetic rate has therefore been fitted on field data by inverse modelling: 1.5 × 10- 5 molchalk L - 1water year - 1. Sensitivity analysis indicates that the CO2 partial pressure of the unsaturated zone is a critical parameter for modelling the baseline chemistry over the whole chalk aquifer.

Morphogen and proinflammatory cytokine release kinetics from PRGF-Endoret fibrin scaffolds: evaluation of the effect of leukocyte inclusion.

PubMed

Anitua, E; Zalduendo, M M; Prado, R; Alkhraisat, M H; Orive, G

2015-03-01

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cytokines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.

Engineering multi-stage nanovectors for controlled degradation and tunable release kinetics

PubMed Central

Martinez, Jonathan O.; Chiappini, Ciro; Ziemys, Arturas; Faust, Ari M.; Kojic, Milos; Liu, Xuewu; Ferrari, Mauro; Tasciotti, Ennio

2013-01-01

Nanovectors hold substantial promise in abating the off-target effects of therapeutics by providing a means to selectively accumulate payloads at the target lesion, resulting in an increase in the therapeutic index. A sophisticated understanding of the factors that govern the degradation and release dynamics of these nanovectors is imperative to achieve these ambitious goals. In this work, we elucidate the relationship that exists between variations in pore size and the impact on the degradation, loading, and release of multistage nanovectors. Larger pored vectors displayed faster degradation and higher loading of nanoparticles, while exhibiting the slowest release rate. The degradation of these particles was characterized to occur in a multi-step progression where they initially decreased in size leaving the porous core isolated, while the pores gradually increased in size. Empirical loading and release studies of nanoparticles along with diffusion modeling revealed that this prolonged release was modulated by the penetration within the porous core of the vectors regulated by their pore size. PMID:23911070

Determination of differential cross sections and kinetic energy release of co-products from central sliced images in photo-initiated dynamic processes.

PubMed

Chen, Kuo-mei; Chen, Yu-wei

2011-04-07

For photo-initiated inelastic and reactive collisions, dynamic information can be extracted from central sliced images of state-selected Newton spheres of product species. An analysis framework has been established to determine differential cross sections and the kinetic energy release of co-products from experimental images. When one of the reactants exhibits a high recoil speed in a photo-initiated dynamic process, the present theory can be employed to analyze central sliced images from ion imaging or three-dimensional sliced fluorescence imaging experiments. It is demonstrated that the differential cross section of a scattering process can be determined from the central sliced image by a double Legendre moment analysis, for either a fixed or continuously distributed recoil speeds in the center-of-mass reference frame. Simultaneous equations which lead to the determination of the kinetic energy release of co-products can be established from the second-order Legendre moment of the experimental image, as soon as the differential cross section is extracted. The intensity distribution of the central sliced image, along with its outer and inner ring sizes, provide all the clues to decipher the differential cross section and the kinetic energy release of co-products.

Oxidative dissolution of silver nanoparticles: A new theoretical approach.

PubMed

Adamczyk, Zbigniew; Oćwieja, Magdalena; Mrowiec, Halina; Walas, Stanisław; Lupa, Dawid

2016-05-01

A general model of an oxidative dissolution of silver particle suspensions was developed that rigorously considers the bulk and surface solute transport. A two-step surface reaction scheme was proposed that comprises the formation of the silver oxide phase by direct oxidation and the acidic dissolution of this phase leading to silver ion release. By considering this, a complete set of equations is formulated describing oxygen and silver ion transport to and from particles' surfaces. These equations are solved in some limiting cases of nanoparticle dissolution in dilute suspensions. The obtained kinetic equations were used for the interpretation of experimental data pertinent to the dissolution kinetics of citrate-stabilized silver nanoparticles. In these kinetic measurements the role of pH and bulk suspension concentration was quantitatively evaluated by using the atomic absorption spectrometry (AAS). It was shown that the theoretical model adequately reflects the main features of the experimental results, especially the significant increase in the dissolution rate for lower pH. Also the presence of two kinetic regimes was quantitatively explained in terms of the decrease in the coverage of the fast dissolving oxide layer. The overall silver dissolution rate constants characterizing these two regimes were determined. Copyright © 2015 Elsevier Inc. All rights reserved.

Aging of vitrified wastes: An experimental and analogical approach

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

Sterpenich, J.; Forestier, L. Le; Libourel, G.

1995-12-31

In order to tackle the problems of the longevity of vitrified wastes, the authors used two complementary approaches: an analogical approach to examine the leaching processes of vitreous matrices as a function of time and to evaluate the longevity of vitrified wastes, and an experimental approach based on leaching experiments which allowed the determination of the rate and the kinetics of release of each element under well known conditions. Despite the very different durations of alteration, around 1,000 years for the medieval stained glasses and several weeks for leaching experiments, the authors show that the results obtained in laboratory andmore » under natural conditions are comparable. Thus, studies of medieval stained glasses allow prediction of the alteration of vitreous matrices and in particular, of vitrified wastes, and can be used to determine the rates and kinetics of release of pollutants. Medieval stained glasses furnish an excellent model for understanding the aging of vitrified wastes over time periods of up to a thousand years.« less

Transient loading of CD34+ hematopoietic progenitor cells with polystyrene nanoparticles.

PubMed

Deville, Sarah; Hadiwikarta, Wahyu Wijaya; Smisdom, Nick; Wathiong, Bart; Ameloot, Marcel; Nelissen, Inge; Hooyberghs, Jef

2017-01-01

CD34 + hematopoietic progenitor cells (HPCs) offer great opportunities to develop new treatments for numerous malignant and non-malignant diseases. Nanoparticle (NP)-based strategies can further enhance this potential, and therefore a thorough understanding of the loading behavior of HPCs towards NPs is essential for a successful application. The present study focusses on the interaction kinetics of 40 nm sized carboxylated polystyrene (PS) NPs with HPCs. Interestingly, a transient association of the NPs with HPCs is observed, reaching a maximum within 1 hour and declining afterwards. This behavior is not seen in dendritic cells (CD34-DCs) differentiated from HPCs, which display a monotonic increase in NP load. We demonstrate that this transient interaction requires an energy-dependent cellular process, suggesting active loading and release of NPs by HPCs. This novel observation offers a unique approach to transiently equip HPCs. A simple theoretical approach modeling the kinetics of NP loading and release is presented, contributing to a framework of describing this phenomenon.

Layered double hydroxide using hydrothermal treatment: morphology evolution, intercalation and release kinetics of diclofenac sodium

NASA Astrophysics Data System (ADS)

Joy, Mathew; Iyengar, Srividhya J.; Chakraborty, Jui; Ghosh, Swapankumar

2017-12-01

The present work demonstrates the possibilities of hydrothermal transformation of Zn-Al layered double hydroxide (LDH) nanostructure by varying the synthetic conditions. The manipulation in washing step before hydrothermal treatment allows control over crystal morphologies, size and stability of their aqueous solutions. We examined the crystal growth process in the presence and the absence of extra ions during hydrothermal treatment and its dependence on the drug (diclofenac sodium (Dic-Na)) loading and release processes. Hexagonal plate-like crystals show sustained release with ˜90% of the drug from the matrix in a week, suggesting the applicability of LDH nanohybrids in sustained drug delivery systems. The fits to the release kinetics data indicated the drug release as a diffusion-controlled release process. LDH with rod-like morphology shows excellent colloidal stability in aqueous suspension, as studied by photon correlation spectroscopy.

Direct evidence for kinetic effects associated with solar wind reconnection

PubMed Central

Xu, Xiaojun; Wang, Yi; Wei, Fengsi; Feng, Xueshang; Deng, Xiaohua; Ma, Yonghui; Zhou, Meng; Pang, Ye; Wong, Hon-Cheng

2015-01-01

Kinetic effects resulting from the two-fluid physics play a crucial role in the fast collisionless reconnection, which is a process to explosively release massive energy stored in magnetic fields in space and astrophysical plasmas. In-situ observations in the Earth's magnetosphere provide solid consistence with theoretical models on the point that kinetic effects are required in the collisionless reconnection. However, all the observations associated with solar wind reconnection have been analyzed in the context of magnetohydrodynamics (MHD) although a lot of solar wind reconnection exhausts have been reported. Because of the absence of kinetic effects and substantial heating, whether the reconnections are still ongoing when they are detected in the solar wind remains unknown. Here, by dual-spacecraft observations, we report a solar wind reconnection with clear Hall magnetic fields. Its corresponding Alfvenic electron outflow jet, derived from the decouple between ions and electrons, is identified, showing direct evidence for kinetic effects that dominate the collisionless reconnection. The turbulence associated with the exhaust is a kind of background solar wind turbulence, implying that the reconnection generated turbulence has not much developed. PMID:25628139

Direct evidence for kinetic effects associated with solar wind reconnection.

PubMed

Xu, Xiaojun; Wang, Yi; Wei, Fengsi; Feng, Xueshang; Deng, Xiaohua; Ma, Yonghui; Zhou, Meng; Pang, Ye; Wong, Hon-Cheng

2015-01-28

Kinetic effects resulting from the two-fluid physics play a crucial role in the fast collisionless reconnection, which is a process to explosively release massive energy stored in magnetic fields in space and astrophysical plasmas. In-situ observations in the Earth's magnetosphere provide solid consistence with theoretical models on the point that kinetic effects are required in the collisionless reconnection. However, all the observations associated with solar wind reconnection have been analyzed in the context of magnetohydrodynamics (MHD) although a lot of solar wind reconnection exhausts have been reported. Because of the absence of kinetic effects and substantial heating, whether the reconnections are still ongoing when they are detected in the solar wind remains unknown. Here, by dual-spacecraft observations, we report a solar wind reconnection with clear Hall magnetic fields. Its corresponding Alfvenic electron outflow jet, derived from the decouple between ions and electrons, is identified, showing direct evidence for kinetic effects that dominate the collisionless reconnection. The turbulence associated with the exhaust is a kind of background solar wind turbulence, implying that the reconnection generated turbulence has not much developed.

Cobalt, chromium and molybdenum ions kinetics in the human body: data gained from a total hip replacement with massive third body wear of the head and neuropathy by cobalt intoxication.

PubMed

Pazzaglia, U E; Apostoli, P; Congiu, T; Catalani, S; Marchese, M; Zarattini, G

2011-09-01

A patient with a total hip replacement developed optic, acoustic and peripheral neuropathy from metal ions intoxication, due to the wear products released from the prosthesis. Subsequently the kinetics of the metal ions was studied. Massive wear and acute intoxication allowed a study of the metal ions kinetics and of EDTA treatment. Plasma and other organic fluids were saturated by each of the metal ions released from the exposed surface according to the solubility of each ion; a larger fraction of Co ions was bound within red cells, while the plasmatic fraction appeared more movable. In a patient with a prosthesis subjected to wear, the ions released are from the prosthetic and from the debris surface (spread in the body). The latter is a function of the number and size of particles. Revision of the prosthesis from the point of view of the metal ions kinetics corresponded to a reduction of the releasing surface because of debris washed out by irrigation and tissue excision; however, the metal particles spread by lymphatic circulation continued to release ions even though the source of wear had been removed. Early diagnosis of high metal wear can be ascertained with mass spectrometry and after revision high levels of metal ions can only be reduced with repeated chelating treatment. It is preferable not to revise fractured ceramic components with a polyethylene-metal articulation.

Computational Modeling of Neurotransmitter Release Evoked by Electrical Stimulation: Nonlinear Approaches to Predicting Stimulation-Evoked Dopamine Release.

PubMed

Trevathan, James K; Yousefi, Ali; Park, Hyung Ook; Bartoletta, John J; Ludwig, Kip A; Lee, Kendall H; Lujan, J Luis

2017-02-15

Neurochemical changes evoked by electrical stimulation of the nervous system have been linked to both therapeutic and undesired effects of neuromodulation therapies used to treat obsessive-compulsive disorder, depression, epilepsy, Parkinson's disease, stroke, hypertension, tinnitus, and many other indications. In fact, interest in better understanding the role of neurochemical signaling in neuromodulation therapies has been a focus of recent government- and industry-sponsored programs whose ultimate goal is to usher in an era of personalized medicine by creating neuromodulation therapies that respond to real-time changes in patient status. A key element to achieving these precision therapeutic interventions is the development of mathematical modeling approaches capable of describing the nonlinear transfer function between neuromodulation parameters and evoked neurochemical changes. Here, we propose two computational modeling frameworks, based on artificial neural networks (ANNs) and Volterra kernels, that can characterize the input/output transfer functions of stimulation-evoked neurochemical release. We evaluate the ability of these modeling frameworks to characterize subject-specific neurochemical kinetics by accurately describing stimulation-evoked dopamine release across rodent (R 2 = 0.83 Volterra kernel, R 2 = 0.86 ANN), swine (R 2 = 0.90 Volterra kernel, R 2 = 0.93 ANN), and non-human primate (R 2 = 0.98 Volterra kernel, R 2 = 0.96 ANN) models of brain stimulation. Ultimately, these models will not only improve understanding of neurochemical signaling in healthy and diseased brains but also facilitate the development of neuromodulation strategies capable of controlling neurochemical release via closed-loop strategies.

Kinetic modeling of light limitation and sulfur deprivation effects in the induction of hydrogen production with Chlamydomonas reinhardtii: Part I. Model development and parameter identification.

PubMed

Fouchard, Swanny; Pruvost, Jérémy; Degrenne, Benoit; Titica, Mariana; Legrand, Jack

2009-01-01

Chlamydomonas reinhardtii is a green microalga capable of turning its metabolism towards H2 production under specific conditions. However this H2 production, narrowly linked to the photosynthetic process, results from complex metabolic reactions highly dependent on the environmental conditions of the cells. A kinetic model has been developed to relate culture evolution from standard photosynthetic growth to H2 producing cells. It represents transition in sulfur-deprived conditions, known to lead to H2 production in Chlamydomonas reinhardtii, and the two main processes then induced which are an over-accumulation of intracellular starch and a progressive reduction of PSII activity for anoxia achievement. Because these phenomena are directly linked to the photosynthetic growth, two kinetic models were associated, the first (one) introducing light dependency (Haldane type model associated to a radiative light transfer model), the second (one) making growth a function of available sulfur amount under extracellular and intracellular forms (Droop formulation). The model parameters identification was realized from experimental data obtained with especially designed experiments and a sensitivity analysis of the model to its parameters was also conducted. Model behavior was finally studied showing interdependency between light transfer conditions, photosynthetic growth, sulfate uptake, photosynthetic activity and O2 release, during transition from oxygenic growth to anoxic H2 production conditions.

A combined chitosan/nano-size hydroxyapatite system for the controlled release of icariin.

PubMed

Fan, Junjun; Bi, Long; Wu, Tao; Cao, Liangguo; Wang, Dexin; Nan, Kaihui; Chen, Jingdi; Jin, Dan; Jiang, Shan; Pei, Guoxian

2012-02-01

Icariin, a plant-derived flavonol glycoside, has been proved as an osteoinductive agent for bone regeneration. For this reason, we developed an icariin-loaded chitosan/nano-sized hydroxyapatite (IC-CS/HA) system which controls the release kinetics of icariin to enhance bone repairing. First, by Fourier transform infrared spectroscopy, we found that icariin was stable in the system developed without undergoing any chemical changes. On the other hand, X-ray diffraction, scanning electron microscopy and mechanical test revealed that the introduction of icariin did not remarkably change the phase, morphology, porosity and mechanical strength of the CS/HA composite. Then the hydrolytic degradation and drug release kinetics in vitro were investigated by incubation in phosphate buffered saline solution. The results indicated that the icariin was released in a temporally controlled manner and the release kinetics could be governed by degradation of both chitosan and hydroxyapatite matrix. Finally the in vitro bioactivity assay revealed that the loaded icariin was biologically active as evidenced by stimulation of bone marrow derived stroma cell alkaline phosphatase activity and formation of mineralized nodules. This successful IC-CS/HA system offers a new delivery method of osteoinductive agents and a useful scaffold design for bone regeneration.

Preparation and characterization of cross-linked excipient of coprocessed xanthan gum-acacia gum as matrix for sustained release tablets

NASA Astrophysics Data System (ADS)

Surini, Silvia; Wati, Dina Risma; Syahdi, Rezi Riadhi

2018-02-01

Sustained release tablet is solid dosage form which is designed to release drugs slowly in the body. This research was intended to prepare and characterize the cross-linked excipients of co-processed xanthan gum-acacia gum (CL-Co-XGGA) as matrices for sustained release tablets with gliclazide as a model drug. CL-Co-XGGA excipients were cross-linked materials of co-processed excipients of xanthan gum-acacia gum (Co-XGGA) using sodium trimetaphosphate. Co-processed excipients of xanthan gum-acacia gum were prepared in the ratio of each excipient 1:2, 1:1 and 2:1. Co-XGGA and CL-Co-XGGA excipients were characterized physically, chemically and functionally. Then, the sustained release (SR) tablets were formulated by wet granulation method using CL-Co-XGGA excipients as matrices. Also, the dissolution study of the gliclazide SR tablets was carried out in phosphate buffer medium pH 7,4 containing sodium lauryl sulphate 0.2% for 12 hours. The results showed that the degree of substitution (DS) of CL-Co-XGGA 1:2, 1:1, 2:1 excipients were respectively 0.067, 0.082 and 0.08. Besides that, the excipients gel strengths were 14.03, 17.27 and 20,70 gF, respectively. The cross-linked excipients had improved flow properties and swelling capability compared to the Co-XGGA excipients. The results of the gliclazide SR tablets evaluations showed that all tablets were passed all tablet requirements. Moreover, the gliclazide release from SR tablets F1 - F6 revealed the sustained release profile, which was following zero order kinetics (F1, F2, F3, F6) and Higuchi kinetics (F4 and F5). It could be concluded that the obtained CL-Co-XGGA excipients might be used as matrices for sustained release tablets and could retard drug release up to 8 until 32 hours.

Influence of polymer network parameters of tragacanth gum-based pH responsive hydrogels on drug delivery.

PubMed

Singh, Baljit; Sharma, Vikrant

2014-01-30

The present article deals with design of tragacanth gum-based pH responsive hydrogel drug delivery systems. The characterization of hydrogels has been carried out by SEMs, EDAX, FTIR, (13)C NMR, XRD, TGA/DTA/DTG and swelling studies. The correlation between reaction conditions and structural parameters of polymer networks such as polymer volume fraction in the swollen state (ϕ), Flory-Huggins interaction parameter (χ), molecular weight of the polymer chain between two neighboring cross links (M¯c), crosslink density (ρ) and mesh size (ξ) has been determined. The different kinetic models such as zero order, first order, Higuchi square root law, Korsmeyer-Peppas model and Hixson-Crowell cube root model were applied and it has been observed that release profile of amoxicillin best followed the first order model for the release of drug from the polymer matrix. The swelling of the hydrogels and release of drug from the drug loaded hydrogels occurred through non-Fickian diffusion mechanism in pH 7.4 solution. Copyright © 2013 Elsevier Ltd. All rights reserved.

A quantitative model for oxygen uptake and release in a family of hemeproteins.

PubMed

Bustamante, Juan P; Szretter, María E; Sued, Mariela; Martí, Marcelo A; Estrin, Darío A; Boechi, Leonardo

2016-06-15

Hemeproteins have many diverse functions that largely depend on the rate at which they uptake or release small ligands, like oxygen. These proteins have been extensively studied using either simulations or experiments, albeit only qualitatively and one or two proteins at a time. We present a physical-chemical model, which uses data obtained exclusively from computer simulations, to describe the uptake and release of oxygen in a family of hemeproteins, called truncated hemoglobins (trHbs). Through a rigorous statistical analysis we demonstrate that our model successfully recaptures all the reported experimental oxygen association and dissociation kinetic rate constants, thus allowing us to establish the key factors that determine the rates at which these hemeproteins uptake and release oxygen. We found that internal tunnels as well as the distal site water molecules control ligand uptake, whereas oxygen stabilization by distal site residues controls ligand release. Because these rates largely determine the functions of these hemeproteins, these approaches will also be important tools in characterizing the trHbs members with unknown functions. lboechi@ic.fcen.uba.ar Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Deposition and transport of Pseudomonas aeruginosa in porous media: lab-scale experiments and model analysis.

PubMed

Kwon, Kyu-Sang; Kim, Song-Bae; Choi, Nag-Choul; Kim, Dong-Ju; Lee, Soonjae; Lee, Sang-Hyup; Choi, Jae-Woo

2013-01-01

In this study, the deposition and transport of Pseudomonas aeruginosa on sandy porous materials have been investigated under static and dynamic flow conditions. For the static experiments, both equilibrium and kinetic batch tests were performed at a 1:3 and 3:1 soil:solution ratio. The batch data were analysed to quantify the deposition parameters under static conditions. Column tests were performed for dynamic flow experiments with KCl solution and bacteria suspended in (1) deionized water, (2) mineral salt medium (MSM) and (3) surfactant + MSM. The equilibrium distribution coefficient (K(d)) was larger at a 1:3 (2.43 mL g(-1)) than that at a 3:1 (0.28 mL g(-1)) soil:solution ratio. Kinetic batch experiments showed that the reversible deposition rate coefficient (k(att)) and the release rate coefficient (k(det)) at a soil:solution ratio of 3:1 were larger than those at a 1:3 ratio. Column experiments showed that an increase in ionic strength resulted in a decrease in peak concentration of bacteria, mass recovery and tailing of the bacterial breakthrough curve (BTC) and that the presence of surfactant enhanced the movement of bacteria through quartz sand, giving increased mass recovery and tailing. Deposition parameters under dynamic condition were determined by fitting BTCs to four different transport models, (1) kinetic reversible, (2) two-site, (3) kinetic irreversible and (4) kinetic reversible and irreversible models. Among these models, Model 4 was more suitable than the others since it includes the irreversible sorption term directly related to the mass loss of bacteria observed in the column experiment. Applicability of the parameters obtained from the batch experiments to simulate the column breakthrough data is evaluated.

Kinetic analysis of an anion exchange absorbent for CO2 capture from ambient air.

PubMed

Shi, Xiaoyang; Li, Qibin; Wang, Tao; Lackner, Klaus S

2017-01-01

This study reports a preparation method of a new moisture swing sorbent for CO2 capture from air. The new sorbent components include ion exchange resin (IER) and polyvinyl chloride (PVC) as a binder. The IER can absorb CO2 when surrounding is dry and release CO2 when surrounding is wet. The manuscript presents the studies of membrane structure, kinetic model of absorption process, performance of desorption process and the diffusivity of water molecules in the CO2 absorbent. It has been proved that the kinetic performance of CO2 absorption/desorption can be improved by using thin binder and hot water treatment. The fast kinetics of P-100-90C absorbent is due to the thin PVC binder, and high diffusion rate of H2O molecules in the sample. The impressive is this new CO2 absorbent has the fastest CO2 absorption rate among all absorbents which have been reported by other up-to-date literatures.

Kinetic analysis of an anion exchange absorbent for CO2 capture from ambient air

PubMed Central

Shi, Xiaoyang; Li, Qibin; Lackner, Klaus S.

2017-01-01

This study reports a preparation method of a new moisture swing sorbent for CO2 capture from air. The new sorbent components include ion exchange resin (IER) and polyvinyl chloride (PVC) as a binder. The IER can absorb CO2 when surrounding is dry and release CO2 when surrounding is wet. The manuscript presents the studies of membrane structure, kinetic model of absorption process, performance of desorption process and the diffusivity of water molecules in the CO2 absorbent. It has been proved that the kinetic performance of CO2 absorption/desorption can be improved by using thin binder and hot water treatment. The fast kinetics of P-100-90C absorbent is due to the thin PVC binder, and high diffusion rate of H2O molecules in the sample. The impressive is this new CO2 absorbent has the fastest CO2 absorption rate among all absorbents which have been reported by other up-to-date literatures. PMID:28640914

Pharmacokinetic modeling of 4,4'-methylenedianiline released from reused polyurethane dialyzer potting materials.

PubMed

Do Luu, H M; Hutter, J C

2000-01-01

4, 4'-Methylenedianiline (MDA) is a hydrolysis degradation product that can be released from polyurethanes commonly used in medical device applications. MDA is mutagenic and carcinogenic in animals. In humans, it is hepatotoxic, a known contact and respiratory allergen, and a suspected carcinogen. A physiologically based pharmacokinetic (PBPK) model was developed to estimate the absorption, distribution, metabolism, and excretion of MDA in patients exposed to MDA leached from the potting materials of hemodialyzers. A worst-case reuse situation and a single use case were investigated. The PBPK model included five tissue compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues, and richly perfused tissues. Physiological and chemical parameters of a healthy individual used in the model were obtained from the literature. The model was calibrated using previously published kinetic studies of IV administered doses of (14) C-MDA to rats. The model was validated using independent data published for MDA-exposed workers. The PBPK results indicated that dialysis patients who are exposed to MDA released from dialyzers (new or reused) could accumulate low levels of MDA and metabolites (total MDA) over time. Copyright 2000 John Wiley & Sons, Inc.

Poliovirus Cell Entry: Common Structural Themes in Viral Cell Entry Pathways

PubMed Central

Hogle, James M.

2006-01-01

Structural studies of polio- and closely related viruses have provided a series of snapshots along their cell entry pathways. Based on the structures and related kinetic, biochemical, and genetic studies, we have proposed a model for the cell entry pathway for polio- and closely related viruses. In this model a maturation cleavage of a capsid protein precursor locks the virus in a metastable state, and the receptor acts like a transition-state catalyst to overcome an energy barrier and release the mature virion from the metastable state. This initiates a series of conformational changes that allow the virus to attach to membranes, form a pore, and finally release its RNA genome into the cytoplasm. This model has striking parallels with emerging models for the maturation and cell entry of more complex enveloped viruses such as influenza virus and HIV. PMID:12142481

Controllable mineral coatings on scaffolds as carriers for growth factor release for bone tissue engineering

NASA Astrophysics Data System (ADS)

Saurez-Gonzalez, Darilis

The work presented in this document, focused on the development and characterization of mineral coatings on scaffold materials to serve as templates for growth factor binding and release. Mineral coatings were formed using a biomimetic approach that consisted in the incubation of scaffolds in modified simulated body fluids (mSBF). To modulate the properties of the mineral coating, which we hypothesized would dictate growth factor release, we used carbonate (HCO3) concentration in mSBF of 4.2 mM, 25mM, and 100mM. Analysis of the mineral coatings formed using scanning electron microscopy indicated growth of a continuous layer of mineral with different morphologies. X-ray diffraction analysis showed peaks associated with hydroxyapatite. FTIR data confirmed the substitution of HCO3 in the mineral. As the extent of HCO3 substitution increased, the coating exhibited more rapid dissolution kinetics in an environment deficient in calcium and phosphate. The mineral coatings provided an effective mechanism for bioactive growth factor binding and release. Peptide versions of vascular endothelial growth factor (VEGF) and bone morphogenetic protein 2 (BMP2) were bound with efficiencies up to 90% to mineral-coated PCL scaffolds. Recombinant human vascular endothelial growth factor (rhVEGF) also bound to mineral coated scaffolds with lower efficiency (20%) and released with faster release kinetics compared to peptides growth factor. Released rhVEGF induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro and enhanced blood vessel formation in vivo in an intramuscular sheep model. In addition to the use the mineral coatings for single growth factor release, we expanded the concept and bound both an angiogenic (rhVEGF) and osteogenic (mBMP2) growth factor by a simple double dipping process. Sustained release of both growth factors was demonstrated for over 60 days. Released rhVEGF enhanced blood vessel formation in vivo in sheep and its biological activity was not affected by the presence of mBMP2. The approach for growth factor binding and release from mineral coatings can be adapted to different materials and medical devices and provide a simple and adaptable mechanism for sustained release of single or dual growth factors.

Tellurium-containing polymer micelles: competitive-ligand-regulated coordination responsive systems.

PubMed

Cao, Wei; Gu, Yuwei; Meineck, Myriam; Li, Tianyu; Xu, Huaping

2014-04-02

Nanomaterials capable of achieving tunable cargo release kinetics are of significance in a fundamental sense and various biological or medical applications. We report a competitive coordination system based on a novel tellurium-containing polymer and its ligand-regulated release manners. Tellurium was introduced to water-soluble polymers for the first time as drug delivery vehicles. The coordination chemistry between platinum and tellurium was designed to enable the load of platinum-based drugs. Through the competitive coordination of biomolecules, the drugs could be released in a controlled manner. Furthermore, the release kinetics could be modulated by the competitive ligands involved due to their different coordination ability. This tellurium-containing polymer may enrich the family of delivery systems and provide a new platform for future biomedical nanotechnologies.

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products

DOE PAGES

Green, Amy M.; Barber, Victoria P.; Fang, Yi; ...

2017-11-06

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH 3CHOO. IR excitation of selectively deuterated syn-CD 3CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn-CD 3CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, whichmore » is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ~10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. Lastly, at 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn-CH 3CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ~50.« less

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

Cassingham, N.; Corkhill, C. L.; Backhouse, D. J.

The first comprehensive assessment of the dissolution kinetics of simulant Magnox–THORP blended UK high-level waste glass, obtained by performing a range of single-pass flow-through experiments, is reported here. Inherent forward rates of glass dissolution were determined over a temperature range of 23 to 70°C and an alkaline pH range of 8.0 to 12.0. Linear regression techniques were applied to the TST kinetic rate law to obtain fundamental parameters necessary to model the dissolution kinetics of UK high-level waste glass (the activation energy (Ea), pH power law coefficient (η) and the intrinsic rate constant (k0)), which is of importance to themore » post-closure safety case for the geological disposal of vitreous products. The activation energies based on B release ranged from 55 ± 3 to 83 ± 9 kJ mol–1, indicating that Magnox–THORP blend glass dissolution has a surface-controlled mechanism, similar to that of other high- level waste simulant glass compositions such as the French SON68 and LAW in the US. Forward dissolution rates, based on Si, B and Na release, suggested that the dissolution mechanism under dilute conditions, and pH and temperature ranges of this study, was not sensitive to composition as defined by HLW-incorporation rate.« less

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products

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

Green, Amy M.; Barber, Victoria P.; Fang, Yi

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH 3CHOO. IR excitation of selectively deuterated syn-CD 3CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn-CD 3CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, whichmore » is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ~10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. Lastly, at 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn-CH 3CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ~50.« less

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products.

PubMed

Green, Amy M; Barber, Victoria P; Fang, Yi; Klippenstein, Stephen J; Lester, Marsha I

2017-11-21

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH 3 CHOO. IR excitation of selectively deuterated syn -CD 3 CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn -CD 3 CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, which is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ∼10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. At 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn -CH 3 CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ∼50.

Selective deuteration illuminates the importance of tunneling in the unimolecular decay of Criegee intermediates to hydroxyl radical products

PubMed Central

Green, Amy M.; Barber, Victoria P.; Fang, Yi; Klippenstein, Stephen J.; Lester, Marsha I.

2017-01-01

Ozonolysis of alkenes, an important nonphotolytic source of hydroxyl (OH) radicals in the atmosphere, proceeds through unimolecular decay of Criegee intermediates. Here, we report a large kinetic isotope effect associated with the rate-limiting hydrogen-transfer step that releases OH radicals for a prototypical Criegee intermediate, CH3CHOO. IR excitation of selectively deuterated syn-CD3CHOO is shown to result in deuterium atom transfer and release OD radical products. Vibrational activation of syn-CD3CHOO is coupled with direct time-resolved detection of OD products to measure a 10-fold slower rate of unimolecular decay upon deuteration in the vicinity of the transition state barrier, which is confirmed by microcanonical statistical theory that incorporates quantum mechanical tunneling. The corresponding kinetic isotope effect of ∼10 is attributed primarily to the decreased probability of D-atom vs. H-atom transfer arising from tunneling. Master equation modeling is utilized to compute the thermal unimolecular decay rates for selectively and fully deuterated syn methyl-substituted Criegee intermediates under atmospheric conditions. At 298 K (1 atm), tunneling is predicted to enhance the thermal decay rate of syn-CH3CHOO compared with the deuterated species, giving rise to a significant kinetic isotope effect of ∼50. PMID:29109292

Darwin's bee-trap: The kinetics of Catasetum, a new world orchid.

PubMed

Nicholson, Charles C; Bales, James W; Palmer-Fortune, Joyce E; Nicholson, Robert G

2008-01-01

The orchid genera Catasetum employs a hair-trigger activated, pollen release mechanism, which forcibly attaches pollen sacs onto foraging insects in the New World tropics. This remarkable adaptation was studied extensively by Charles Darwin and he termed this rapid response "sensitiveness." Using high speed video cameras with a frame speed of 1000 fps, this rapid release was filmed and from the subsequent footage, velocity, speed, acceleration, force and kinetic energy were computed.

Processing of extraterrestrial materials by high temperature vacuum vaporization

NASA Technical Reports Server (NTRS)

Grimley, R. T.; Lipschutz, M. E.

1983-01-01

It is noted that problems associated with the extraction and concentration of elements and commpounds important for the construction and operation of space habitats have received little attention. High temperature vacuum vaporization is considered a promising approach; this is a technique for which the space environment offers advantages in the form of low ambient pressures and temperatures and the possibility of sustained high temperatures via solar thermal energy. To establish and refine this new technology, experimental determinations must be made of the material release profiles as a function of temperature, of the release kinetics and chemical forms of material being transported, and of the various means of altering release kinetics. Trace element data determined by neutron activation analysis of meteorites heated to 1400 C in vacuum is summarized. The principal tool, high temperature spectrometry, is used to examine the vaporization thermodynamics and kinetics of major and minor elements from complex multicomponent extraterrestrial materials.

Co-delivery of cisplatin and doxorubicin from calcium phosphate beads/matrix scaffolds for osteosarcoma therapy.

PubMed

Hess, Ulrike; Shahabi, Shakiba; Treccani, Laura; Streckbein, Philipp; Heiss, Christian; Rezwan, Kurosch

2017-08-01

Bone substitute materials with a controlled drug release ability can fill cavities caused by the resection of bone tumours and thereby combat any leftover bone cancer cells. The combined release of different cytostatics seems to enhance their toxicity. In this study, calcium phosphate beads and matrix scaffolds are combined for a long-term co-delivery of cis-diamminedichloroplatinum (cisplatin, CDDP) and doxorubicin hydrochloride (DOX) as clinical relevant model drugs. Tricalcium phosphate/alginate beads as additional drug carrier are produced by droplet extrusion with ionotropic gelation and incorporated in scaffold matrix by freeze gelation without sintering. CDDP shows a short burst release while DOX has a continuous release measurable over the entire study period of 40days. Drug release from matrix is decreased by ~30% compared to release from beads. Nevertheless, all formulations follow the Korsmeyer-Peppas release kinetic model and show Fickian diffusion. Cytotoxic activity was conducted on MG-63 osteosarcoma cells after 1, 4, and 7days with WST-1 cell viability assay. Co-loaded composites enhance activity towards MG-63 cells up to ~75% toxicity while reducing the released drug quantity. The results suggest that co-loaded beads/matrix scaffolds are highly promising for osteosarcoma therapy due to synergistic effects over a long period of more than a month. Copyright © 2017 Elsevier B.V. All rights reserved.

Lactose digestion by human jejunal biopsies: the relationship between hydrolysis and absorption.

PubMed Central

Dawson, D J; Lobley, R W; Burrows, P C; Miller, V; Holmes, R

1986-01-01

The relationship between lactose hydrolysis and absorption of released glucose was investigated by determining the kinetics of lactose digestion by jejunal biopsies incubated in vitro. Lactase activity in intact biopsies correlated with conventional assay of tissue homogenates (r = 0.85, p less than 0.001), and glucose uptake from 28 mM lactose was directly proportional to lactase activity (r = 0.95, p less than 0.001) in 21 subjects with normal lactase levels, six with hypolactasia (primary or secondary to coeliac disease) and two with lactose intolerance but normal lactase activity. Kinetic analysis at 0.56-56 mM lactose in five normal subjects showed saturable kinetics for hydrolysis (app Km = 33.9 +/- 2.2 mM; app Vmax = 26.5 +/- 1.1 nmol/min/mg dry weight) but glucose uptake could be fitted to a model either of saturable uptake (app Kt = 47.2 +/- 0.3 mM; app Jmax = 14.1 +/- 0.2 nmol/min/mg) or saturable uptake plus a linear component (app Kt = 21.3 +/- 1.15; app Jmax = 4.59 +/- 0.12; app Kd = 0.093 +/- 0.010 nmol/min/mg/mM). The proportion of glucose taken into the tissue did not significantly exceed 50% of the total released at any lactose concentration suggesting the lack of an efficient capture mechanism for the released glucose. The results suggest that lactose hydrolysis is the rate limiting step in the overall absorption of glucose from lactose in vitro, and that the relationship between hydrolysis and absorption is the same in normal subjects and in hypolactasic subjects. PMID:3084346

The Effect of Ethanol Addition to Gasoline on Low- and Intermediate-Temperature Heat Release under Boosted Conditions in Kinetically Controlled Engines

NASA Astrophysics Data System (ADS)

Vuilleumier, David Malcolm

The detailed study of chemical kinetics in engines has become required to further advance engine efficiency while simultaneously lowering engine emissions. This push for higher efficiency engines is not caused by a lack of oil, but by efforts to reduce anthropogenic carbon dioxide emissions, that cause global warming. To operate in more efficient manners while reducing traditional pollutant emissions, modern internal combustion piston engines are forced to operate in regimes in which combustion is no longer fully transport limited, and instead is at least partially governed by chemical kinetics of combusting mixtures. Kinetically-controlled combustion allows the operation of piston engines at high compression ratios, with partially-premixed dilute charges; these operating conditions simultaneously provide high thermodynamic efficiency and low pollutant formation. The investigations presented in this dissertation study the effect of ethanol addition on the low-temperature chemistry of gasoline type fuels in engines. These investigations are carried out both in a simplified, fundamental engine experiment, named Homogeneous Charge Compression Ignition, as well as in more applied engine systems, named Gasoline Compression Ignition engines and Partial Fuel Stratification engines. These experimental investigations, and the accompanying modeling work, show that ethanol is an effective scavenger of radicals at low temperatures, and this inhibits the low temperature pathways of gasoline oxidation. Further, the investigations measure the sensitivity of gasoline auto-ignition to system pressure at conditions that are relevant to modern engines. It is shown that at pressures above 40 bar and temperatures below 850 Kelvin, gasoline begins to exhibit Low-Temperature Heat Release. However, the addition of 20% ethanol raises the pressure requirement to 60 bar, while the temperature requirement remains unchanged. These findings have major implications for a range of modern engines. Low-Temperature Heat Release significantly enhances the auto-ignition process, which limits the conditions under which advanced combustion strategies may operate. As these advanced combustion strategies are required to meet emissions and fuel-economy regulations, the findings of this dissertation may benefit and be incorporated into future engine design toolkits, such as detailed chemical kinetic mechanisms.

Simultaneous recording of t-tubular electrical activity and Ca2+-release in heart failure

NASA Astrophysics Data System (ADS)

Crocini, C.; Coppini, R.; Ferrantini, C.; Yan, P.; Loew, L.; Tesi, C.; Poggesi, C.; Cerbai, E.; Pavone, F. S.; Sacconi, L.

2014-05-01

T-tubules (TT) are invaginations of the surface sarcolemma (SS) that mediate the rapid propagation of the action potential (AP) to the cardiomyocyte core. We employed the advantages of an ultrafast random access multi-photon (RAMP) microscope (Sacconi et al., PNAS 2012) with a double staining approach to optically record t-tubular AP and, simultaneously, the corresponding local Ca2+-release in different positions across the cardiomyocytes. Despite a uniform AP between SS and TT at steady-state stimulation, in control cardiomyocytes we observed a non-negligible be variability of local Ca2+-transient amplitude and kinetics. This variability was significantly reduced by applying 0.1μM Isoproterenol, which increases the opening probability of Ca2+-release units. In the rat heart failure model (HF), we previously demonstrated that some tubular elements fail to propagate AP. We found that the tubules unable to propagate AP, displayed a reduced correspondent Ca2+-transient amplitude as well as a slower Ca2+ rise compared to electrically coupled tubules. Moreover variability of Ca2+-transient kinetics were increased in HF. Finally, TT that did not show AP, occasionally exhibited spontaneous depolarizations that were never accompanied by local Ca2+-release in the absence of any pro-arrhythmogenic stimulation. Simultaneous recording of AP and Ca2+-transient allows us to probe the spatio-temporal variability of Ca2+-release, whereas the investigation of Ca2+-transient in HF discloses an unexpected uncoupling between t-tubular depolarization and Ca2+-release in remodeled tubules. This work was funded by the European Union 7th Framework Program (FP7/2007- 2013) under grant agreement n° 284464, 241526, by the Italian Ministry of University and Research (NANOMAX), and by Telethon-Italy (GGP13162).

Evaluation of acetylated moth bean starch as a carrier for controlled drug delivery

PubMed Central

Singh, Akhilesh V.; Nath, Lila K.

2012-01-01

The present investigation concerns with the development of controlled release tablets of lamivudine using acetylated moth bean starch. The acetylated starch was synthesized with acetic anhydride in pyridine medium. The acetylated moth bean starch was tested for acute toxicity and drug–excipient compatibility study. The formulations were evaluated for physical characteristics like hardness, friability, % drug content and weight variations. The in vitro release study showed that the optimized formulation exhibited highest correlation (R) value in case of Higuchi kinetic model and the release mechanism study proved that the formulation showed a combination of diffusion and erosion process. There was a significant difference in the pharmacokinetic parameters (Tmax, Cmax, AUC, Vd, T1/2 and MDT) of the optimized formulation as compared to the marketed conventional tablet Lamivir®, which proved controlled release potential of acetylated moth bean starch. PMID:22210486

PVP VA64 as a novel release-modifier for sustained-release mini-matrices prepared via hot melt extrusion.

PubMed

Li, Yongcheng; Lu, Ming; Wu, Chuanbin

2017-11-10

The purpose of this study was to explore poly(vinylpyrrolidone-co-vinyl acetate) (PVP VA64) as a novel release-modifier to tailor the drug release from ethylcellulose (EC)-based mini-matrices prepared via hot melt extrusion (HME). Quetiapine fumarate (QF) was selected as model drug. QF/EC/PVP VA64 mini-matrices were extruded with 30% drug loading. The physical state of QF in extruded mini-matrices was characterized using differential scanning calorimetry, X-ray powder diffraction, and confocal Raman microscopy. The release-controlled ability of PVP VA64 was investigated and compared with that of xanthan gum, crospovidone, and low-substituted hydroxypropylcellulose. The influences of PVP VA64 content and processing temperature on QF release behavior and mechanism were also studied. The results indicated QF dispersed as the crystalline state in all mini-matrices. The release of QF from EC was very slow as only 4% QF was released in 24 h. PVP VA64 exhibited the best ability to enhance the drug release as compared with other three release-modifiers. The drug release increased to 50-100% in 24 h with the addition of 20-40% PVP VA64. Increasing processing temperature slightly slowed down the drug release by decreasing free volume and pore size. The release kinetics showed good fit with the Ritger-Peppas model. The values of release exponent (n) increased as PVP VA64 is added (0.14 for pure EC, 0.41 for 20% PVP VA64, and 0.61 for 40% PVP VA64), revealing that the addition of PVP VA64 enhanced the erosion mechanism. This work presented a new polymer blend system of EC with PVP VA64 for sustained-release prepared via HME.

Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses.

PubMed

Helassa, Nordine; Dürst, Céline D; Coates, Catherine; Kerruth, Silke; Arif, Urwa; Schulze, Christian; Wiegert, J Simon; Geeves, Michael; Oertner, Thomas G; Török, Katalin

2018-05-22

Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGlu f ) and ultrafast (iGlu u ) variants with comparable brightness but increased K d for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGlu u has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGlu u is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGlu u responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons. Copyright © 2018 the Author(s). Published by PNAS.

Energy transformations associated with the synoptic and planetary scales during the evolution of a blocking anticyclone and an upstream explosively-developing cyclone

NASA Technical Reports Server (NTRS)

Smith, Phillip J.; Tsou, Chih-Hua

1992-01-01

The eddy kinetic energy (KE), release of eddy potential energy, generation of eddy kinetic energy, and exchange between eddy and zonal kinetic energy are investigated for a blocking anticyclone over the North Atlantic Ocean and an extratropical cyclone that developed during January 17-21, 1979. The results indicate that KE was maintained by baroclinic conversion of potential to kinetic. As released potential energy was being used to generate KE, a portion of the KE was barotropically converted to zonal KE. These transformations were dominated by the synoptic-scale component. While changes in the mass field depended not only on the synoptic scale but also on the interactions between the synoptic and planetary scales, the corresponding changes in the eddy motion fields responded largely to synoptic-scale processes.

Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage.

PubMed

Kaleemullah, M; Jiyauddin, K; Thiban, E; Rasha, S; Al-Dhalli, S; Budiasih, S; Gamal, O E; Fadli, A; Eddy, Y

2017-07-01

Currently, the use of natural gums and mucilage is of increasing importance in pharmaceutical formulations as valuable drug excipient. Natural plant-based materials are economic, free of side effects, biocompatible and biodegradable. Therefore, Ketoprofen matrix tablets were formulated by employing Hibiscus rosa-sinensis leaves mucilage as natural polymer and HPMC (K100M) as a synthetic polymer to sustain the drug release from matrix system. Direct compression method was used to develop sustained released matrix tablets. The formulated matrix tablets were evaluated in terms of physical appearance, weight variation, thickness, diameter, hardness, friability and in vitro drug release. The difference between the natural and synthetic polymers was investigated concurrently. Matrix tablets developed from each formulation passed all standard physical evaluation tests. The dissolution studies of formulated tablets revealed sustained drug release up to 24 h compared to the reference drug Apo Keto® SR tablets. The dissolution data later were fitted into kinetic models such as zero order equation, first order equation, Higuchi equation, Hixson Crowell equation and Korsmeyer-Peppas equation to study the release of drugs from each formulation. The best formulations were selected based on the similarity factor ( f 2 ) value of 50% and more. Through the research, it is found that by increasing the polymers concentration, the rate of drug release decreased for both natural and synthetic polymers. The best formulation was found to be F3 which contained 40% Hibiscus rosa-sinensis mucilage polymer and showed comparable dissolution profile to the reference drug with f 2 value of 78.03%. The release kinetics of this formulation has shown to follow non-Fickian type which involved both diffusion and erosion mechanism. Additionally, the statistical results indicated that there was no significant difference (p > 0.05) between the F3 and reference drug in terms of MDT and T50% with p-values of 1.00 and 0.995 respectively.

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

PubMed

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

2015-03-01

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

Insulin released from titanium discs with insulin coatings-Kinetics and biological activity.

PubMed

Malekzadeh, B Ö; Ransjo, M; Tengvall, P; Mladenovic, Z; Westerlund, A

2017-10-01

Local administration of insulin from a titanium surface has been demonstrated to increase bone formation in non-diabetic rats. The authors hypothesized that insulin was released from the titanium surface and with preserved biological activity after the release. Thus, in the present in vitro study, human recombinant insulin was immobilized onto titanium discs, and the insulin release kinetics was evaluated using Electro-chemiluminescence immunoassay. Neutral Red uptake assay and mineralization assay were used to evaluate the biological effects of the released insulin on human osteoblast-like MG-63 cells. The results confirmed that insulin was released from titanium surfaces during a six-week period. Etching the disc prior to insulin coating, thickening of the insulin coating and incubation of the discs in serum-enriched cell culture medium increased the release. However, longer storage time decreased the release of insulin. Furthermore, the released insulin had retained its biological activity, as demonstrated by the significant increase in cell number and a stimulated mineralization process, upon exposure to released insulin. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1847-1854, 2017. © 2016 Wiley Periodicals, Inc.

Impact of human milk pasteurization on the kinetics of peptide release during in vitro dynamic term newborn digestion.

PubMed

Deglaire, Amélie; De Oliveira, Samira C; Jardin, Julien; Briard-Bion, Valérie; Emily, Mathieu; Ménard, Olivia; Bourlieu, Claire; Dupont, Didier

2016-07-01

Holder pasteurization (62.5°C, 30 min) ensures sanitary quality of donor's human milk but also denatures beneficial proteins. Understanding whether this further impacts the kinetics of peptide release during gastrointestinal digestion of human milk was the aim of the present paper. Mature raw (RHM) or pasteurized (PHM) human milk were digested (RHM, n = 2; PHM, n = 3) by an in vitro dynamic system (term stage). Label-free quantitative peptidomics was performed on milk and digesta (ten time points). Ascending hierarchical clustering was conducted on "Pasteurization × Digestion time" interaction coefficients. Preproteolysis occurred in human milk (159 unique peptides; RHM: 91, PHM: 151), mostly on β-casein (88% of the endogenous peptides). The predicted cleavage number increased with pasteurization, potentially through plasmin activation (plasmin cleavages: RHM, 53; PHM, 76). During digestion, eight clusters resumed 1054 peptides from RHM and PHM, originating for 49% of them from β-casein. For seven clusters (57% of peptides), the kinetics of peptide release differed between RHM and PHM. The parent protein was significantly linked to the clustering (p-value = 1.4 E-09), with β-casein and lactoferrin associated to clusters in an opposite manner. Pasteurization impacted selectively gastric and intestinal kinetics of peptide release in term newborns, which may have further nutritional consequences. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Oral insulin delivery using P(MAA-g-EG) hydrogels: effects of network morphology on insulin delivery characteristics.

PubMed

Nakamura, Koji; Murray, Robert J; Joseph, Jeffrey I; Peppas, Nicholas A; Morishita, Mariko; Lowman, Anthony M

2004-03-24

Hydrogels of poly(methacrylic acid-g-ethylene glycol) were prepared using different reaction water contents in order to vary the network mesh size, swelling behavior and insulin loading/release kinetics. Gels prepared with greater reaction solvent contents swelled to a greater degree and had a larger network mesh size. All of the hydrogels were able to incorporate insulin and protected it from release in acidic media. At higher pH (7.4), the release rates increased with reaction solvent content. Using a closed loop animal model, all of the insulin loaded formulations produced significant insulin absorption in the upper small intestine combined with hypoglycemic effects. In these studies, bioavailabilities ranged from 4.6% to 7.2% and were dependent on reaction solvent content.

Investigation of surfactant/cosurfactant synergism impact on ibuprofen solubilization capacity and drug release characteristics of nonionic microemulsions.

PubMed

Djekic, Ljiljana; Primorac, Marija; Filipic, Slavica; Agbaba, Danica

2012-08-20

The current study investigates the performances of the multicomponent mixtures of nonionic surfactants regarding the microemulsion stabilisation, drug solubilization and in vitro drug release kinetic. The primary surfactant was PEG-8 caprylic/capric glycerides (Labrasol). The cosurfactants were commercially available mixtures of octoxynol-12 and polysorbate 20 without or with the addition of PEG-40 hydrogenated castor oil (Solubilisant gamma 2421 and Solubilisant gamma 2429, respectively). The oil phase of microemulsions was isopropyl myristate. Phase behaviour study of the pseudo-ternary systems Labrasol/cosurfactant/oil/water at surfactant-to-cosurfactant weight ratios (K(m)) 40:60, 50:50 and 60:40, revealed a strong synergism in the investigated tensides mixtures for stabilisation of microemulsions containing up to 80% (w/w) of water phase at surfactant +cosurfactant-to-oil weight ratio (SCoS/O) 90:10. Solubilization of a model drug ibuprofen in concentration common for topical application (5%, w/w) was achieved at the water contents below 50% (w/w). Drug free and ibuprofen-loaded microemulsions M1-M6, containing 45% (w/w) of water phase, were prepared and characterized by polarized light microscopy, conductivity, pH, rheological and droplet size measurements. In vitro ibuprofen release kinetics from the microemulsions was investigated using paddle-over-enhancer cell method and compared with the commercial 5% (w/w) ibuprofen hydrogel product (Deep Relief, Mentholatum Company Ltd., USA). The investigated microemulsions were isotropic, low viscous Bingham-type liquids with the pH value (4.70-6.61) suitable for topical application. The different efficiency of the tensides mixtures for microemulsion stabilisation was observed, depending on the cosurfactant type and K(m) value. Solubilisant gamma 2429 as well as higher K(m) (i.e., lower relative content of the cosurfactant) provided higher surfactant/cosurfactant synergism. The drug molecules were predominantly solubilized within the interface film. The amount of drug released from the formulations M3 (10.75%, w/w) and M6 (13.45%, w/w) (K(m) 60:40) was limited in comparison with the reference (22.22%, w/w) and follows the Higuchi model. Microemulsions M2 and M5 (K(m) 50:50) gave zero order drug release pattern and ∼15% (w/w) ibuprofen released. The release profiles from microemulsions M1 and M4 (K(m) 40:60) did not fit well with the models used for analysis, although the amounts of ibuprofen released (24.47%, w/w) and 17.99% (w/w), respectively) were comparable to that of the reference hydrogel. The drug release mechanism was related with the surfactant/cosurfactant synergism, thus the lower efficiency of the tensides corresponded to the faster drug release. Copyright © 2012 Elsevier B.V. All rights reserved.

A single mutation in a tunnel to the active site changes the mechanism and kinetics of product release in haloalkane dehalogenase LinB.

PubMed

Biedermannová, Lada; Prokop, Zbyněk; Gora, Artur; Chovancová, Eva; Kovács, Mihály; Damborsky, Jiří; Wade, Rebecca C

2012-08-17

Many enzymes have buried active sites. The properties of the tunnels connecting the active site with bulk solvent affect ligand binding and unbinding and also the catalytic properties. Here, we investigate ligand passage in the haloalkane dehalogenase enzyme LinB and the effect of replacing leucine by a bulky tryptophan at a tunnel-lining position. Transient kinetic experiments show that the mutation significantly slows down the rate of product release. Moreover, the mechanism of bromide ion release is changed from a one-step process in the wild type enzyme to a two-step process in the mutant. The rate constant of bromide ion release corresponds to the overall steady-state turnover rate constant, suggesting that product release became the rate-limiting step of catalysis in the mutant. We explain the experimental findings by investigating the molecular details of the process computationally. Analysis of trajectories from molecular dynamics simulations with a tunnel detection software reveals differences in the tunnels available for ligand egress. Corresponding differences are seen in simulations of product egress using a specialized enhanced sampling technique. The differences in the free energy barriers for egress of a bromide ion obtained using potential of mean force calculations are in good agreement with the differences in rates obtained from the transient kinetic experiments. Interactions of the bromide ion with the introduced tryptophan are shown to affect the free energy barrier for its passage. The study demonstrates how the mechanism of an enzymatic catalytic cycle and reaction kinetics can be engineered by modification of protein tunnels.

Temperature Dependence of Proton Electroreduction Kinetics at Gold(111) and (210) Surfaces

DTIC Science & Technology

1991-05-31

Temperature Dependence of Proton Electroreduction Kinetics at Gold (111) and (210) Surfaces 12 PERSONAL AUTHOR(S) A. Hamelin, L. Stoicoviciu, S.-C...Technical Report No. 98 Temperature Dependence of Proton Electroreduction Kinetics at Gold (lll) and (210) Surfaces by A. Hamelin, L. Stoicoviciu, S...approved for public release and sale: its distribution is unlimited. Temperature Dependence of Proton Electroreduction Kinetics at Gold (Ill) and (210

Polymer Nanosheet Containing Star-Like Copolymers: A Novel Scalable Controlled Release System.

PubMed

Cao, Peng-Fei; de Leon, Al; Rong, Lihan; Yin, Ke-Zhen; Abenojar, Eric C; Su, Zhe; Tiu, Brylee David B; Exner, Agata A; Baer, Eric; Advincula, Rigoberto C

2018-04-26

Poly(ε-caprolactone) (PCL)-based nanomaterials, such as nanoparticles and liposomes, have exhibited great potential as controlled release systems, but the difficulties in large-scale fabrication limit their practical applications. Among the various methods being developed to fabricate polymer nanosheets (PNSs) for different applications, such as Langmuir-Blodgett technique and layer-by-layer assembly, are very effort consuming, and only a few PNSs can be obtained. In this paper, poly(ε-caprolactone)-based PNSs with adjustable thickness are obtained in large quantity by simple water exposure of multilayer polymer films, which are fabricated via a layer multiplying coextrusion method. The PNS is also demonstrated as a novel controlled guest release system, in which release kinetics are adjustable by the nanosheet thickness, pH values of the media, and the presence of protecting layers. Theoretical simulations, including Korsmeyer-Peppas model and Finite-element analysis, are also employed to discern the observed guest-release mechanisms. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analytical solutions for coagulation and condensation kinetics of composite particles

NASA Astrophysics Data System (ADS)

Piskunov, Vladimir N.

2013-04-01

The processes of composite particles formation consisting of a mixture of different materials are essential for many practical problems: for analysis of the consequences of accidental releases in atmosphere; for simulation of precipitation formation in clouds; for description of multi-phase processes in chemical reactors and industrial facilities. Computer codes developed for numerical simulation of these processes require optimization of computational methods and verification of numerical programs. Kinetic equations of composite particle formation are given in this work in a concise form (impurity integrated). Coagulation, condensation and external sources associated with nucleation are taken into account. Analytical solutions were obtained in a number of model cases. The general laws for fraction redistribution of impurities were defined. The results can be applied to develop numerical algorithms considerably reducing the simulation effort, as well as to verify the numerical programs for calculation of the formation kinetics of composite particles in the problems of practical importance.

Study of Enzymatic Hydrolysis of Fructans from Agave salmiana Characterization and Kinetic Assessment

PubMed Central

Michel-Cuello, Christian; Ortiz-Cerda, Imelda; Moreno-Vilet, Lorena; Grajales-Lagunes, Alicia; Moscosa-Santillán, Mario; Bonnin, Johanne; González-Chávez, Marco Martín; Ruiz-Cabrera, Miguel

2012-01-01

Fructans were extracted from Agave salmiana juice, characterized and subjected to hydrolysis process using a commercial inulinase preparation acting freely. To compare the performance of the enzymatic preparation, a batch of experiments were also conducted with chicory inulin (reference). Hydrolysis was performed for 6 h at two temperatures (50, 60°C) and two substrate concentrations (40, 60 mg/ml). Hydrolysis process was monitored by measuring the sugars released and residual substrate by HPLC. A mathematical model which describes the kinetics of substrate degradation as well as fructose production was proposed to analyze the hydrolysis assessment. It was found that kinetics were significantly influenced by temperature, substrate concentration, and type of substrate (P < 0.01). The extent of substrate hydrolysis varied from 82 to 99%. Hydrolysis product was mainly constituted of fructose, obtaining from 77 to 96.4% of total reducing sugars. PMID:22629216

Influence of dialkyne structure on the properties of new click-gels based on hyaluronic acid.

PubMed

Testa, Gabriella; Di Meo, Chiara; Nardecchia, Stefania; Capitani, Donatella; Mannina, Luisa; Lamanna, Raffaele; Barbetta, Andrea; Dentini, Mariella

2009-08-13

Hydrogels have been widely used in tissue engineering as a support for tissue formation and/or to deliver drug locally. A novel procedure for the in situ rapid chemical gelation of aqueous solutions of hyaluronan (HA) was employed. HA was functionalised with an arm bearing a terminal azido group (HAAA). When HAAA was mixed with a series of dialkyne reagents of different length, a 1,3-dipolar cycloaddition ("click-chemistry") reaction took place in the presence of catalytic amount of Cu(I) resulting in fast gelation at room temperature. The resulting gels were characterised in terms of degree of cross-linking by (1)H HR-MAS NMR. The kinetic of gelation and the determination of elastic moduli as well as the degree of swelling and the controlled release of a model drug, were studied as a function of chemical nature of the dialkyne group, catalyst concentration, HAAA concentration and temperature. All these variables allowed the swelling ratio and the extent of release of a drug, doxorubicin, entrapped within the gel, to be modulated. In all cases the kinetic of release reached the stationary state within 150 h. The height of the plateau was dependent on the overall (chemical and topological) degree of cross-linking.

Qualification of CASMO5 / SIMULATE-3K against the SPERT-III E-core cold start-up experiments

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

Grandi, G.; Moberg, L.

SIMULATE-3K is a three-dimensional kinetic code applicable to LWR Reactivity Initiated Accidents. S3K has been used to calculate several international recognized benchmarks. However, the feedback models in the benchmark exercises are different from the feedback models that SIMULATE-3K uses for LWR reactors. For this reason, it is worth comparing the SIMULATE-3K capabilities for Reactivity Initiated Accidents against kinetic experiments. The Special Power Excursion Reactor Test III was a pressurized-water, nuclear-research facility constructed to analyze the reactor kinetic behavior under initial conditions similar to those of commercial LWRs. The SPERT III E-core resembles a PWR in terms of fuel type, moderator,more » coolant flow rate, and system pressure. The initial test conditions (power, core flow, system pressure, core inlet temperature) are representative of cold start-up, hot start-up, hot standby, and hot full power. The qualification of S3K against the SPERT III E-core measurements is an ongoing work at Studsvik. In this paper, the results for the 30 cold start-up tests are presented. The results show good agreement with the experiments for the reactivity initiated accident main parameters: peak power, energy release and compensated reactivity. Predicted and measured peak powers differ at most by 13%. Measured and predicted reactivity compensations at the time of the peak power differ less than 0.01 $. Predicted and measured energy release differ at most by 13%. All differences are within the experimental uncertainty. (authors)« less

ScrumPy: metabolic modelling with Python.

PubMed

Poolman, M G

2006-09-01

ScrumPy is a software package used for the definition and analysis of metabolic models. It is written using the Python programming language that is also used as a user interface. ScrumPy has features for both kinetic and structural modelling, but the emphasis is on structural modelling and those features of most relevance to analysis of large (genome-scale) models. The aim is at describing ScrumPy's functionality to readers with some knowledge of metabolic modelling, but implementation, programming and other computational details are omitted. ScrumPy is released under the Gnu Public Licence, and available for download from http://mudshark.brookes.ac.uk/ ScrumPy.

Mesoporous silica formulation strategies for drug dissolution enhancement: a review.

PubMed

McCarthy, Carol A; Ahern, Robert J; Dontireddy, Rakesh; Ryan, Katie B; Crean, Abina M

2016-01-01

Silica materials, in particular mesoporous silicas, have demonstrated excellent properties to enhance the oral bioavailability of poorly water-soluble drugs. Current research in this area is focused on investigating the kinetic profile of drug release from these carriers and manufacturing approaches to scale-up production for commercial manufacture. This review provides an overview of different methods utilized to load drugs onto mesoporous silica carriers. The influence of silica properties and silica pore architecture on drug loading and release are discussed. The kinetics of drug release from mesoporous silica systems is examined and the manufacturability and stability of these formulations are reviewed. Finally, the future prospects of mesoporous silica drug delivery systems are considered. Substantial progress has been made in the characterization and development of mesoporous drug delivery systems for drug dissolution enhancement. However, more research is required to fully understand the drug release kinetic profile from mesoporous silica materials. Incomplete drug release from the carrier and the possibility of drug re-adsorption onto the silica surface need to be investigated. Issues to be addressed include the manufacturability and regulation status of formulation approaches employing mesoporous silica to enhance drug dissolution. While more research is needed to support the move of this technology from the bench to a commercial medicinal product, it is a realistic prospect for the near future.

The ameliorated longevity and pharmacokinetics of valsartan released from a gel system of ultradeformable vesicles.

PubMed

Ahad, Abdul; Aqil, Mohd; Kohli, Kanchan; Sultana, Yasmin; Mujeeb, Mohd

2016-09-01

The present study traces the development and characterization of the gel formulation of valsartan-loaded ultradeformable vesicles for management of hypertension. The prepared gel formulation of ultradeformable vesicles was evaluated for in vitro skin permeation, release kinetics, skin irritation, pharmacokinetics, and stability. The in vitro skin permeation study showed that the gel formulation of ultradeformable vesicles presented a flux value of 368.74 μg/cm(2)/h, in comparison to that of the traditional liposomal gel formulation, with an enhancement ratio of 26.91, through rat skin. The data for release kinetics showed that the release profile followed zero-order kinetics, and that the drug release mechanism was non-Fickian. The results of the skin irritation study demonstrated that the prepared formulation was safe, less irritant, and well-tolerated for transdermal delivery. The results of the pharmacokinetic study demonstrated that the AUC value of valsartan after transdermal administration was apparently increased. The formulation stored under a refrigerated condition showed greater stability, and results were found to be within the specification under storage conditions. It is evident from this study that the gel formulation of ultradeformable vesicles of valsartan is a promising delivery system for lipophilic drugs, and has reasonably good stability characteristics.

Demonstration of Anisotropic Fluid Closure Capturing the Kinetic Structure of Magnetic Reconnection

NASA Astrophysics Data System (ADS)

Ohia, Obioma

2012-10-01

Magnetic reconnection in collisionless plasmas plays an important role in space and laboratory plasmas. Allowing magnetic stress to be reduced by a rearrangement of magnetic line topology, this process is often accompanied by a large release of magnetic field energy, which can heat the plasma, drive large scale flows, or accelerate particles. Reconnection has been widely studied through fluid models and kinetic simulations. While two-fluid models often reproduce the fast reconnection that is observed in nature and seen in kinetic simulations, it is found that the structure surrounding the electron diffusion region and the electron current layer differ vastly between fluid models and kinetic simulations [1]. Recently, using an adiabatic solution of the Vlasov equation, a new fluid closure has been obtained for electrons that relate parallel and perpendicular pressures to the density and magnetic field [2]. Here we present the results of fluid simulation, developed using the HiFi framework [3], that implements new equations of state for guide-field reconnection. The new fluid closure accurately accounts for the anisotropic electron pressure that builds in the reconnection region due to electric and magnetic trapping of electrons. In contrast to previous fluid models, our fluid simulation reproduces the detailed reconnection region as observed in fully kinetic simulations [4]. We hereby demonstrate that the new fluid closure self-consistently captures all the physics relevant to the structure of the reconnection region, providing a gateway to a renewed and deeper theoretical understanding for reconnection in weakly collisional regimes.[4pt] [1] Daughton W et al., Phys. Plasmas 13, 072101 (2006).[0pt] [2] Le A et al., Phys. Rev. Lett. 102, 085001 (2009). [0pt] [3] Lukin VS, Linton MG, Nonlinear Proc. Geoph. 18, 871 (2011). [0pt] [4] Ohia O, et al., Phys. Rev. Lett. In Press (2012).

Towards elucidation of the drug release mechanism from compressed hydrophilic matrices made of cellulose ethers. III. Critical use of thermodynamic parameters of activation for modeling the water penetration and drug release processes.

PubMed

Ferrero, Carmen; Massuelle, Danielle; Jeannerat, Damien; Doelker, Eric

2013-09-10

The two main purposes of this work were: (i) to critically consider the use of thermodynamic parameters of activation for elucidating the drug release mechanism from hydroxypropyl methylcellulose (HPMC) matrices, and (ii) to examine the effect of neutral (pH 6) and acidic (pH 2) media on the release mechanism. For this, caffeine was chosen as model drug and various processes were investigated for the effect of temperature and pH: caffeine diffusion in solution and HPMC gels, and drug release from and water penetration into the HPMC tablets. Generally, the kinetics of the processes was not significantly affected by pH. As for the temperature dependence, the activation energy (E(a)) values calculated from caffeine diffusivities were in the range of Fickian transport (20-40 kJ mol⁻¹). Regarding caffeine release from HPMC matrices, fitting the profiles using the Korsmeyer-Peppas model would indicate anomalous transport. However, the low apparent E(a) values obtained were not compatible with a swelling-controlled mechanism and can be assigned to the dimensional change of the system during drug release. Unexpectedly, negative apparent E(a) values were calculated for the water uptake process, which can be ascribed to the exothermic dissolution of water into the initially dry HPMC, the expansion of the matrix and the polymer dissolution. Taking these contributions into account, the true E(a) would fall into the range valid for Fickian diffusion. Consequently, a relaxation-controlled release mechanism can be dismissed. The apparent anomalous drug release from HPMC matrices results from a coupled Fickian diffusion-erosion mechanism, both at pH 6 and 2. Copyright © 2013 Elsevier B.V. All rights reserved.

Reactive transport modelling of groundwater chemistry in a chalk aquifer at the watershed scale.

PubMed

Mangeret, A; De Windt, L; Crançon, P

2012-09-01

This study investigates thermodynamics and kinetics of water-rock interactions in a carbonate aquifer at the watershed scale. A reactive transport model is applied to the unconfined chalk aquifer of the Champagne Mounts (France), by considering both the chalk matrix and the interconnected fracture network. Major element concentrations and main chemical parameters calculated in groundwater and their evolution along flow lines are in fair agreement with field data. A relative homogeneity of the aquifer baseline chemistry is rapidly reached in terms of pH, alkalinity and Ca concentration since calcite equilibrium is achieved over the first metres of the vadose zone. However, incongruent chalk dissolution slowly releases Ba, Mg and Sr in groundwater. Introducing dilution effect by rainwater infiltration and a local occurrence of dolomite improves the agreement between modelling and field data. The dissolution of illite and opal-CT, controlling K and SiO(2) concentrations in the model, can be approximately tackled by classical kinetic rate laws, but not the incongruent chalk dissolution. An apparent kinetic rate has therefore been fitted on field data by inverse modelling: 1.5×10(-5) mol(chalk)L (-1) water year (-1). Sensitivity analysis indicates that the CO(2) partial pressure of the unsaturated zone is a critical parameter for modelling the baseline chemistry over the whole chalk aquifer. Copyright © 2012 Elsevier B.V. All rights reserved.

A spring-matrix model for pigment translocation in the red ovarian chromatophores of the freshwater shrimp Macrobrachium olfersi (Crustacea, Decapoda).

PubMed

Boyle, Robert Tew; McNamara, John Campbell

2008-04-01

A model for intracellular transport of pigment granules in the red ovarian chromatophores of the freshwater shrimp Macrobrachium olfersi is proposed on the basis of shifts in the equilibrium of resting forces acting on an elastic pigment matrix. The model describes a pigment-transport mechanism in which mechanochemical protein motors like kinesin and myosin alternately stretch and compress a structurally unified, elastic pigment matrix. Quantifiable properties of the spring-matrix obey Hooke's Law during the rapid phases of pigment aggregation and dispersion. The spring-like response of the pigment mass is estimated from previous kinetic experiments on pigment translocation induced by red pigment concentrating hormone, or by the calcium ionophore A23187. Both translocation effectors trigger an initial phase of rapid pigment aggregation, and their removal or washout after complete aggregation produces a phase of rapid pigment dispersion, followed by slow pigment translocation. The rapid-phase kinetics of pigment transport are in reasonable agreement with Hooke's Law, suggesting that such phases represent the release of kinetic energy, probably produced by the mechanochemical protein motors and stored in the form of matrix deformation during the slow phases of translocation. This semiquantitative model should aid in analyzing intracellular transport systems that incorporate an elastic component.

Adsorption-desorption of oxytetracycline on marine sediments: Kinetics and influencing factors.

PubMed

Li, Jia; Zhang, Hua

2016-12-01

To reveal the kinetics and mechanisms of antibiotic adsorption/desorption processes, batch and stirred flow chamber (SFC) experiments were carried out with oxytetracycline (OTC) on two marine sediments. The OTC adsorption capacities of the marine sediments were relatively weak and related to their organic carbon (OC) and contents of fine particles. Sorption isotherms of OTC on marine sediment can be well described by both the Langmuir and Freundlich models. Langmuir adsorption maxima (q max ) and Freundlich distribution coefficients (K f ) increased with the decrease of salinity and pH, which indicated the importance of variable charged sites on sediment surfaces. A second order kinetic model successfully described adsorption and desorption kinetics of OTC and well reproduced the concentration change during stop-flow. The adsorption kinetic rates (k a ) for OTC under different experimental conditions ranged from 2.00 × 10 -4 to 1.97 × 10 -3  L (mg min) -1 . Results of SFC experiments indicated that diffusive mass transfer was the dominant mechanism of the time-dependent adsorption of OTC and its release from marine sediment was mildly hysteretic. The high desorption percentage (43-75% for LZB and 58-75% for BHB) implied that binding strength of OTC on two marine sediments was weak. In conclusion, marine sediment characteristics and environmental factors such as salinity, pH, and flow rate are critical factors determine extent of OTC sorption on marine sediment and need to be incorporated in modeling fate and transport of OTC in marine environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tamarind seed gum-hydrolyzed polymethacrylamide-g-gellan beads for extended release of diclofenac sodium using 32 full factorial design.

PubMed

Nandi, Gouranga; Nandi, Amit Kumar; Khan, Najim Sarif; Pal, Souvik; Dey, Sibasish

2018-07-15

Development of tamarind seed gum (TSG)-hydrolyzed polymethacrylamide-g-gellan (h-Pmaa-g-GG) composite beads for extended release of diclofenac sodium using 3 2 full factorial design is the main purpose of this study. The ratio of h-Pmaa-g-GG and TSG and concentration of cross-linker CaCl 2 were taken as independent factors with three different levels of each. Effects of polymer ratio and CaCl 2 on drug entrapment efficiency (DEE), drug release, bead size and swelling were investigated. Responses such as DEE and different drug release parameters were statistically analyzed by 3 2 full factorial design using Design-Expert software and finally the formulation factors were optimized to obtain USP-reference release profile. Drug release rate was found to decrease with decrease in the ratio of h-Pmaa-g-GG:TSG and increase in the concentration of Ca 2+ ions in cross-linking medium. The optimized formulation showed DEE of 93.25% and an extended drug release profile over a period of 10h with f 2 =80.13. Kinetic modeling unveiled case-I-Fickian diffusion based drug release mechanism. Copyright © 2018 Elsevier B.V. All rights reserved.

The Kinetic Reaction Mechanism of the Vibrio cholerae Sodium-dependent NADH Dehydrogenase*♦

PubMed Central

Tuz, Karina; Mezic, Katherine G.; Xu, Tianhao; Barquera, Blanca; Juárez, Oscar

2015-01-01

The sodium-dependent NADH dehydrogenase (Na+-NQR) is the main ion transporter in Vibrio cholerae. Its activity is linked to the operation of the respiratory chain and is essential for the development of the pathogenic phenotype. Previous studies have described different aspects of the enzyme, including the electron transfer pathways, sodium pumping structures, cofactor and subunit composition, among others. However, the mechanism of the enzyme remains to be completely elucidated. In this work, we have studied the kinetic mechanism of Na+-NQR with the use of steady state kinetics and stopped flow analysis. Na+-NQR follows a hexa-uni ping-pong mechanism, in which NADH acts as the first substrate, reacts with the enzyme, and the oxidized NAD leaves the catalytic site. In this conformation, the enzyme is able to capture two sodium ions and transport them to the external side of the membrane. In the last step, ubiquinone is bound and reduced, and ubiquinol is released. Our data also demonstrate that the catalytic cycle involves two redox states, the three- and five-electron reduced forms. A model that gathers all available information is proposed to explain the kinetic mechanism of Na+-NQR. This model provides a background to understand the current structural and functional information. PMID:26004776

In Vivo Efficacy of a "Smart" Antimicrobial Implant Coating.

PubMed

Stavrakis, Alexandra I; Zhu, Suwei; Hegde, Vishal; Loftin, Amanda H; Ashbaugh, Alyssa G; Niska, Jared A; Miller, Lloyd S; Segura, Tatiana; Bernthal, Nicholas M

2016-07-20

Postoperative infection is a devastating complication following arthroplasty. The goals of this study were to introduce a "smart" implant coating that combines passive elution of antibiotic with an active-release mechanism that "targets" bacteria, and to use an established in vivo mouse model of post-arthroplasty infection to longitudinally evaluate the efficacy of this polymer implant coating in decreasing bacterial burden. A novel, biodegradable coating using branched poly(ethylene glycol)-poly(propylene sulfide) (PEG-PPS) polymer was designed to deliver antibiotics both passively and actively. In vitro-release kinetics were studied using high-performance liquid chromatography (HPLC) quantification in conditions representing both the physiologic environment and the more oxidative, hyperinflammatory environment of periprosthetic infection. The in vivo efficacy of the PEG-PPS coating delivering vancomycin and tigecycline was tested using an established mouse model of post-arthroplasty infection. Noninvasive bioluminescence imaging was used to quantify the bacterial burden; radiography, to assess osseointegration and bone resorption; and implant sonication, for colony counts. In vitro-release kinetics confirmed passive elution above the minimum inhibitory concentration (MIC). A rapid release of antibiotic was noted when challenged with an oxidative environment (p < 0.05), confirming a "smart" active-release mechanism. The PEG-PPS coating with tigecycline significantly lowered the infection burden on all days, whereas PEG-PPS-vancomycin decreased infection on postoperative day (POD) 1, 3, 5, and 7 (p < 0.05). A mean of 0, 9, and 2.6 × 10(2) colony-forming units (CFUs) grew on culture from the implants treated with tigecycline, vancomycin, and PEG-PPS alone, respectively, and a mean of 1.2 × 10(2), 4.3 × 10(3), and 5.9 × 10(4) CFUs, respectively, on culture of the surrounding tissue (p < 0.05). The PEG-PPS coating provides a promising approach to preventing periprosthetic infection. This polymer is novel in that it combines both passive and active antibiotic-release mechanisms. The tigecycline-based coating outperformed the vancomycin-based coating in this study. PEG-PPS polymer provides a controlled, "smart" local delivery of antibiotics that could be used to prevent postoperative implant-related infections. Copyright © 2016 by The Journal of Bone and Joint Surgery, Incorporated.

Press-coated tablets for time-programmed release of drugs.

PubMed

Conte, U; Maggi, L; Torre, M L; Giunchedi, P; La Manna, A

1993-10-01

A new dry-coated device for the release of drug after a programmable period of time is proposed. It is intended to be used mainly in the therapy of those diseases which depend on circadian rhythms. Some core formulations, characterized by different release rates and mechanisms (containing diltiazem hydrochloride or sodium diclofenac as model drugs), were coated by compression with different polymeric barrier layers (press-coated systems). The shell formulations tested contained either gellable or erodible polymers. The dissolution profiles of uncoated cores and press-coated devices were compared. The gellable and/or erodible characteristics (properties) of the barrier formulations were also examined by means of a penetrometer. The coatings prevent drug release from the core until the polymeric shell is completely eroded or swollen. This delay in release start is not influenced by the core composition and depends only on the shell formulation. Except for the time-lag, the release kinetics of the drug contained in the core are not significantly influenced by the presence of the erodible barrier, but can be widely modulated using a swellable polymeric shell.

APTES-modified mesoporous silicas as the carriers for poorly water-soluble drug. Modeling of diflunisal adsorption and release

NASA Astrophysics Data System (ADS)

Geszke-Moritz, Małgorzata; Moritz, Michał

2016-04-01

Four mesoporous siliceous materials such as SBA-16, SBA-15, PHTS and MCF functionalized with (3-aminopropyl)triethoxysilane were successfully prepared and applied as the carriers for poorly water-soluble drug diflunisal. Several techniques including nitrogen sorption analysis, XRD, TEM, FTIR and thermogravimetric analysis were employed to characterize mesoporous matrices. Adsorption isotherms were analyzed using Langmuir, Freundlich, Temkin and Dubinin-Radushkevich models. In order to find the best-fit isotherm for each model, both linear and nonlinear regressions were carried out. The equilibrium data were best fitted by the Langmuir isotherm model revealing maximum adsorption capacity of 217.4 mg/g for aminopropyl group-modified SBA-15. The negative values of Gibbs free energy change indicated that the adsorption of diflunisal is a spontaneous process. Weibull release model was employed to describe the dissolution profile of diflunisal. At pH 4.5 all prepared mesoporous matrices exhibited the improvement of drug dissolution kinetics as compared to the dissolution rate of pure diflunisal.

Kinetics of Fe Release from Organic Ligand Complexes: Implications for Fe Isotopes?

NASA Astrophysics Data System (ADS)

Nuester, J.; Liermann, L. J.; Brantley, S. L.

2006-12-01

Although iron is the fourth most abundant element in the earth's surface, its bioavailability is limited by its natural tendency to form insoluble iron (oxyhydr)oxides in terrestrial and marine environments. Paradoxically, iron is an essential nutrient for virtually all living cells, so in order to survive, organisms must develop mechanisms to solubilize iron. To acquire iron, organisms synthesize and release iron-specific chelators called siderophores. These siderophores facilitate the transformation of insoluble crystal-bound iron to organically ligand-bound dissolved iron. The reverse process whereby ferric iron is released from siderophores resulting in the precipitation of iron (oxyhydr)oxides or complexation by other iron chelators is an important but not well studied process in the B-horizon of soils. Fe mobility is documented in soils where Fe is often extracted at the top and precipitated at depth. Both the concentration and isotopic signature of Fe varies with depth due to dissolution, precipitation, sorption, and biological processes. Our study is focused on measurement of isotopic fractionation during this reverse process. In a first approach to understand iron liberation form organic ligands, we mimic this process using a reductive mechanism. We use acetohydroxamic acid (aha), EDTA and desferrioxamine B (DFMB) as test ligands to investigate iron release by sodium ascorbate at varying pH. Our first kinetic measurements showed significant differences in iron release depending on pH and stability of the iron complex. Within one hour all iron is released from aha with a small pH effect in the pH range between 4 and 6. In contrast, the pH has a major influence on the iron release from EDTA and DFMB. Depending on pH, total iron is released from EDTA within 24 hours, while only an incomplete iron release from DFMB could be observed within two weeks. These strong kinetic differences in iron release as a consequence of iron reduction are expected to result in significant iron isotope effects, and we are testing for these effects. For example, we expect to see enrichment of light isotopes in the early released fractions as iron is reduced (like effects observed by Wiederhold et al. (2006) for ligand-controlled and reductive dissolution of goethite). Such kinetic isotope effects should be particularly strong for iron release from siderophores with high Fe affinities like DFMB (log ß_(Fe(III)) = 30.60). We are also investigating other mechanisms to liberate iron from organic ligands including a pathway with extracellular iron reductases.

Kinetics of lipid-nanoparticle-mediated intracellular mRNA delivery and function

NASA Astrophysics Data System (ADS)

Zhdanov, Vladimir P.

2017-10-01

mRNA delivery into cells forms the basis for one of the new and promising ways to treat various diseases. Among suitable carriers, lipid nanoparticles (LNPs) with a size of about 100 nm are now often employed. Despite high current interest in this area, the understanding of the basic details of LNP-mediated mRNA delivery and function is limited. To clarify the kinetics of mRNA release from LNPs, the author uses three generic models implying (i) exponential, (ii) diffusion-controlled, and (iii) detachment-controlled kinetic regimes, respectively. Despite the distinct differences in these kinetics, the associated transient kinetics of mRNA translation to the corresponding protein and its degradation are shown to be not too sensitive to the details of the mRNA delivery by LNPs (or other nanocarriers). In addition, the author illustrates how this protein may temporarily influence the expression of one gene or a few equivalent genes. The analysis includes positive or negative regulation of the gene transcription via the attachment of the protein without or with positive or negative feedback in the gene expression. Stable, bistable, and oscillatory schemes have been scrutinized in this context.

Kinetic rate laws of Cd, Pb, and Zn vaporization during municipal solid waste incineration.

PubMed

Falcoz, Quentin; Gauthier, Daniel; Abanades, Stéphane; Flamant, Gilles; Patisson, Fabrice

2009-03-15

The kinetic rate laws of heavy metal (HM) vaporization from municipal solid waste during its incineration were studied. Realistic artificial waste (RAW) samples spiked with Pb, Zn, and Cd were injected into a fluidized bed reactor. Metal vaporization wastracked by continuous measure ofthe above metals in exhaust gases. An inverse model of the reactor was used to calculate the metal vaporization rates from the concentration vs time profiles in the outlet gas. For each metal, experiments were carried out at several temperatures in order to determine the kinetic parameters and to obtain specific rate laws as functions of temperature. Temperature has a strong influence on the HM vaporization dynamics, especially on the vaporization kinetics profile. This phenomenon was attributed to internal diffusion control of the HM release. Two types of kinetic rate laws were established based on temperature: a fourth- or fifth-order polynomial rate law (r(x) = k0e(-E(A)/RT)p(x)) for temperatures lower than 740 degrees C and a first-order polynomial (r(x) = k0e(-E(A)/ RT(q-q(f) for temperatures higher than 740 degrees C.

Release kinetics and cell viability of ibuprofen nanocrystals produced by melt-emulsification.

PubMed

Fernandes, A R; Dias-Ferreira, J; Cabral, C; Garcia, M L; Souto, E B

2018-06-01

The clinical use of poorly water-soluble drugs has become a big challenge in pharmaceutical development due to the compromised bioavailability of the drugs in vivo. Nanocrystals have been proposed as a formulation strategy to improve the dissolution properties of these drugs. The benefits of using nanocrystals in drug delivery, when compared to other nanoparticles, are related to their production facilities, simple structure, and suitability for a variety of administration routes. High pressure homogenization (HPH) is the most promising production process, which can be employed at low or high temperatures. Ibuprofen nanocrystals with a mean size below 175 nm, and polydispersity below 0.18, have been produced by melt-emulsification, followed by HPH. Two nanocrystal formulations, differing on the surfactant composition, have been produced, their in vitro ibuprofen release tested in Franz diffusion cells and adjusted to several kinetic models (zero order, first order, Higuchi, Hixson-Crowell, Korsmeyer-Peppas, Baker-Lonsdale and Weibull model). Cell viability was assessed at 3, 6 and 24 h of incubation on human epithelial colorectal cells (Caco-2) by AlamarBlue ® colorimetric assay. For both formulations, Caco-2 cells viability was dependent on the drug concentration and time of exposure. Copyright © 2018 Elsevier B.V. All rights reserved.

Altered Exocytosis in Chromaffin Cells from Mouse Models of Neurodegenerative Diseases.

PubMed

de Diego, Antonio M G; García, Antonio G

2018-05-09

Chromaffin cells from the adrenal gland (CCs) have extensively been used to explore the molecular structure and function of the exocytotic machinery, neurotransmitter release and synaptic transmission. The CC is integrated in the sympathoadrenal axis that helps the body maintain homeostasis during both routine life and in acute stress conditions. This function is exquisitely controlled by the cerebral cortex and the hypothalamus. We propose the hypothesis that damage undergone by the brain during neurodegenerative diseases is also affecting the neurosecretory function of adrenal medullary CCs. In this context we review here the following themes: (i) how the discharge of catecholamines is centrally and peripherally regulated at the sympatho-adrenal axis; (ii) which are the intricacies of the amperometric techniques used to study the quantal release of single-vesicle exocytotic events; (iii) which are the alterations of the exocytotic fusion pore so far reported, in CCs of mouse models of neurodegenerative diseases; (iv) how some proteins linked to neurodegenerative pathologies affects the kinetics of exocytotic events; (v) finally we try to integrate available data into a hypothesis to explain how the centrally originated neurodegenerative diseases may alter the kinetics of single-vesicle exocytotic events in peripheral adrenal medullary CCs. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Quantitative pharmacological analysis of antagonist binding kinetics at CRF1 receptors in vitro and in vivo

PubMed Central

Ramsey, Simeon J; Attkins, Neil J; Fish, Rebecca; van der Graaf, Piet H

2011-01-01

BACKGROUND AND PURPOSE A series of novel non-peptide corticotropin releasing factor type-1 receptor (CRF1) antagonists were found to display varying degrees of insurmountable and non-competitive behaviour in functional in vitro assays. We describe how we attempted to relate this behaviour to ligand receptor-binding kinetics in a quantitative manner and how this resulted in the development and implementation of an efficient pharmacological screening method based on principles described by Motulsky and Mahan. EXPERIMENTAL APPROACH A non-equilibrium binding kinetic assay was developed to determine the receptor binding kinetics of non-peptide CRF1 antagonists. Nonlinear, mixed-effects modelling was used to obtain estimates of the compounds association and dissociation rates. We present an integrated pharmacokinetic–pharmacodynamic (PKPD) approach, whereby the time course of in vivo CRF1 receptor binding of novel compounds can be predicted on the basis of in vitro assays. KEY RESULTS The non-competitive antagonist behaviour appeared to be correlated to the CRF1 receptor off-rate kinetics. The integrated PKPD model suggested that, at least in a qualitative manner, the in vitro assay can be used to triage and select compounds for further in vivo investigations. CONCLUSIONS AND IMPLICATIONS This study provides evidence for a link between ligand offset kinetics and insurmountable/non-competitive antagonism at the CRF1 receptor. The exact molecular pharmacological nature of this association remains to be determined. In addition, we have developed a quantitative framework to study and integrate in vitro and in vivo receptor binding kinetic behaviour of CRF1 receptor antagonists in an efficient manner in a drug discovery setting. PMID:21449919

Compositional effects on the ignition of FACE gasolines [Compositional effects on the ignition of FACE gasoline fuels: experiments, surrogate fuel formulation, and chemical kinetic modeling

DOE PAGES

Sarathy, S. Mani; Kukkadapu, Goutham; Mehl, Marco; ...

2016-05-08

As regulatory measures for improved fuel economy and decreased emissions are pushing gasoline engine combustion technologies towards extreme conditions (i.e., boosted and intercooled intake with exhaust gas recirculation), fuel ignition characteristics become increasingly important for enabling stable operation. Here, this study explores the effects of chemical composition on the fundamental ignition behavior of gasoline fuels. Two well-characterized, high-octane, non-oxygenated FACE (Fuels for Advanced Combustion Engines) gasolines, FACE F and FACE G, having similar antiknock indices but different octane sensitivities and chemical compositions are studied. Ignition experiments were conducted in shock tubes and a rapid compression machine (RCM) at nominal pressuresmore » of 20 and 40 atm, equivalence ratios of 0.5 and 1.0, and temperatures ranging from 650 to 1270 K. Results at temperatures above 900 K indicate that ignition delay time is similar for these fuels. However, RCM measurements below 900 K demonstrate a stronger negative temperature coefficient behavior for FACE F gasoline having lower octane sensitivity. In addition, RCM pressure profiles under two-stage ignition conditions illustrate that the magnitude of low-temperature heat release (LTHR) increases with decreasing fuel octane sensitivity. However, intermediate-temperature heat release is shown to increase as fuel octane sensitivity increases. Various surrogate fuel mixtures were formulated to conduct chemical kinetic modeling, and complex multicomponent surrogate mixtures were shown to reproduce experimentally observed trends better than simpler two- and three-component mixtures composed of n-heptane, iso-octane, and toluene. Measurements in a Cooperative Fuels Research (CFR) engine demonstrated that the multicomponent surrogates accurately captured the antiknock quality of the FACE gasolines. Simulations were performed using multicomponent surrogates for FACE F and G to reveal the underlying chemical kinetics linking fuel composition with ignition characteristics. Finally, a key discovery of this work is the kinetic coupling between aromatics and naphthenes, which affects the radical pool population and thereby controls ignition.« less

Compositional effects on the ignition of FACE gasolines [Compositional effects on the ignition of FACE gasoline fuels: experiments, surrogate fuel formulation, and chemical kinetic modeling

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

Sarathy, S. Mani; Kukkadapu, Goutham; Mehl, Marco

As regulatory measures for improved fuel economy and decreased emissions are pushing gasoline engine combustion technologies towards extreme conditions (i.e., boosted and intercooled intake with exhaust gas recirculation), fuel ignition characteristics become increasingly important for enabling stable operation. Here, this study explores the effects of chemical composition on the fundamental ignition behavior of gasoline fuels. Two well-characterized, high-octane, non-oxygenated FACE (Fuels for Advanced Combustion Engines) gasolines, FACE F and FACE G, having similar antiknock indices but different octane sensitivities and chemical compositions are studied. Ignition experiments were conducted in shock tubes and a rapid compression machine (RCM) at nominal pressuresmore » of 20 and 40 atm, equivalence ratios of 0.5 and 1.0, and temperatures ranging from 650 to 1270 K. Results at temperatures above 900 K indicate that ignition delay time is similar for these fuels. However, RCM measurements below 900 K demonstrate a stronger negative temperature coefficient behavior for FACE F gasoline having lower octane sensitivity. In addition, RCM pressure profiles under two-stage ignition conditions illustrate that the magnitude of low-temperature heat release (LTHR) increases with decreasing fuel octane sensitivity. However, intermediate-temperature heat release is shown to increase as fuel octane sensitivity increases. Various surrogate fuel mixtures were formulated to conduct chemical kinetic modeling, and complex multicomponent surrogate mixtures were shown to reproduce experimentally observed trends better than simpler two- and three-component mixtures composed of n-heptane, iso-octane, and toluene. Measurements in a Cooperative Fuels Research (CFR) engine demonstrated that the multicomponent surrogates accurately captured the antiknock quality of the FACE gasolines. Simulations were performed using multicomponent surrogates for FACE F and G to reveal the underlying chemical kinetics linking fuel composition with ignition characteristics. Finally, a key discovery of this work is the kinetic coupling between aromatics and naphthenes, which affects the radical pool population and thereby controls ignition.« less

Rapid rates of aerobic methane oxidation at the feather edge of gas hydrate stability in the waters of Hudson Canyon, US Atlantic Margin

NASA Astrophysics Data System (ADS)

Leonte, Mihai; Kessler, John D.; Kellermann, Matthias Y.; Arrington, Eleanor C.; Valentine, David L.; Sylva, Sean P.

2017-05-01

Aerobic oxidation is an important methane sink in seawater overlying gas seeps. Recent surveys have identified active methane seeps in the waters of Hudson Canyon, US Atlantic Margin near the updip limit of methane clathrate hydrate stability. The close proximity of these seeps to the upper stability limit of methane hydrates suggests that changing bottom water temperatures may influence the release rate of methane into the overlying water column. In order to assess the significance of aerobic methane oxidation in limiting the atmospheric expression of methane released from Hudson Canyon, the total extent of methane oxidized along with integrated oxidation rates were quantified. These calculations were performed by combining the measurements of the natural levels of methane concentrations, stable carbon isotopes, and water current velocities into kinetic isotope models yielding rates ranging from 22.8 ± 17 to 116 ± 76 nM/day with an average of 62.7 ± 37 nM/day. Furthermore, an average of 63% of methane released into the water column from an average depth of 515 m was oxidized before leaving this relatively small study area (6.5 km2). Results from the kinetic isotope model were compared to previously-published but concurrently-sampled ex situ measurements of oxidation potential performed using 13C-labeled methane. Ex situ rates were substantially lower, ranging from 0.1 to 22.5 nM/day with an average of 5.6 ± 2.3 nM/day, the discrepancy likely due to the inherent differences between these two techniques. Collectively, the results reveal exceptionally-rapid methane oxidation, with turnover times for methane as low as 0.3-3.7 days, indicating that methane released to the water column is removed quantitatively within the greater extent of Hudson Canyon. The red line represents the original Rayleigh model output, Eq. (1), detailed in the text. The red line represents the original Rayleigh model output, Eq. (1), detailed in the text.

Intercalation and controlled release properties of vitamin C intercalated layered double hydroxide

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

Gao, Xiaorui, E-mail: gxr_1320@sina.com; School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189; Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA

Two drug-inorganic composites involving vitamin C (VC) intercalated in Mg–Al and Mg–Fe layered double hydroxides (LDHs) have been synthesized by the calcination–rehydration (reconstruction) method. Powder X-ray diffraction (XRD), Fourier transform infrared (FTIR), and UV–vis absorption spectroscopy indicate a successful intercalation of VC into the interlayer galleries of the LDH host. Studies of VC release from the LDHs in deionised water and in aqueous CO{sub 3}{sup 2−} solutions imply that Mg{sub 3}Al–VC LDH is a better controlled release system than Mg{sub 3}Fe–VC LDH. Analysis of the release profiles using a number of kinetic models suggests a solution-dependent release mechanism, and amore » diffusion-controlled deintercalation mechanism in deionised water, but an ion exchange process in CO{sub 3}{sup 2−} solution. - Graphical abstract: Vitamin C anions have been intercalated in the interlayer space of layered double hydroxide and released in CO{sub 3}{sup 2−} solution and deionised water. - Highlights: • Vitamin C intercalated Mg–Al and Mg–Fe layered double hydroxides were prepared. • Release property of vitamin C in aqueous CO{sub 3}{sup 2−} solution is better. • Avrami-Erofe’ev and first-order models provide better fit for release results. • Diffusion-controlled and ion exchange processes occur in deionised water. • An ion exchange process occurs in CO{sub 3}{sup 2−} solution.« less

Silver particle monolayers — Formation, stability, applications.

PubMed

Oćwieja, Magdalena; Adamczyk, Zbigniew; Morga, Maria; Kubiak, Katarzyna

2015-08-01

The formation of silver particle monolayers at solid substrates in self-assembly processes is thoroughly reviewed. Initially, various silver nanoparticle synthesis routes are discussed with the emphasis focused on the chemical reduction in aqueous media. Subsequently, the main experimental methods aimed at bulk suspension characterization are critically reviewed by pointing out their advantages and limitations. Also, various methods enabling the in situ studies of particle deposition and release kinetics, especially the streaming potential method are discussed. In the next section, experimental data are invoked illustrating the most important features of particle monolayer formation, in particular, the role of bulk suspension concentration, particle size, ionic strength, temperature and pH. Afterward, the stability of monolayers and particle release kinetics are extensively discussed. The results obtained by the ex situ AFM/SEM imaging of particles are compared with the in situ streaming potential measurements. An equivalency of both methods is demonstrated, especially in respect to the binding energy determination. It is shown that these experimental results can be adequately interpreted in terms of the hybrid theoretical approach that combines the bulk transport step with the surface blocking effects derived from the random sequential adsorption model. It is also concluded that the particle release kinetics is governed by the discrete electrostatic interactions among ion pairs on particle and substrate surfaces. The classical theories based on the mean-field (averaged) zeta potential concept proved inadequate. Using the ion pair concept the minor dependence of the binding energy on particle size, ionic strength, pH and temperature is properly explained. The final sections of this review are devoted to the application of silver nanoparticles and their monolayers in medicine, analytical chemistry and catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

Correlation of in vitro and in vivo paracetamol availability from layered excipient suppositories.

PubMed

Chicco, D; Grabnar, I; Skerjanec, A; Vojnovic, D; Maurich, V; Realdon, N; Ragazzi, E; Belic, A; Karba, R; Mrhar, A

1999-11-05

An in vivo investigation of paracetamol availability was carried out on eight healthy volunteers, comparing two paracetamol suppository formulations prepared using two different gliceride bases, a fast drug-releasing one and a slow drug-releasing one, i.e. Witepsol H15 and W35, respectively. The formulations were selected on the basis of a previous in vitro drug release study, which showed that, by superimposing the excipients in two layers within the same suppository, the drug release kinetics could be modulated using different ratios between the two layers. The comparison between the two different formulations in terms of plasma profiles and total amounts of drug excreted in urine revealed an increase in the extent of drug absorption from the layered excipient suppository. As the W35 has a higher monoglyceride content than the H15, this improved paracetamol availability could be ascribed to the absorption-enhancing effect of the monoglycerides. Moreover, the W35 has also a higher viscosity, which could possibly cause the suppository to be retained for a longer time in the lower part of the rectum, where the blood is drained directly to the systemic circulation. It was therefore hypothesized that the enhanced paracetamol availability could be also due to a liver bypass mechanism. For a further examination of the paracetamol absorption kinetics after rectal administration, a one-compartment model was fitted to the drug plasma concentration data. This approach allowed to draw absorption versus time profiles, which showed that a retardation actually occurred in paracetamol absorption when using suppositories containing the slow drug releasing excipient W35. These absorption data were then employed for an A level in vitro-in vivo correlation testing, and a linear relationship was found between in vitro release rate and in vivo absorption rate, both for fast releasing and for the layered excipient suppositories.

Stability of lime essential oil microparticles produced with protein-carbohydrate blends.

PubMed

Campelo, Pedro Henrique; Sanches, Edgar Aparecido; Fernandes, Regiane Victória de Barros; Botrel, Diego Alvarenga; Borges, Soraia Vilela

2018-03-01

The objective of this work was to analyze the influence of maltodextrin equivalent dextrose on the lime essential oil reconstitution, storage, release and protection properties. Four treatments were evaluated: whey protein concentrate (WPC), and blends of maltodextrin with dextrose equivalents of 5 (WM5), 10 (WM10) and 20 (WM20). The reconstitution and storage properties of the microparticles (solubility, wettability and density), water kinetics adsorption, sorption isotherms, thermogravimetric properties, controlled release and degradation kinetics of encapsulated lime essential oil were studied to measure the quality of the encapsulated materials. The results of the study indicated that the DE degree influences the characteristics of reconstitution, storage, controlled release and degradation characteristics of encapsulated bioactive compounds. The increase in dextrose equivalent improves microparticle solubility, wettability and density, mainly due to the size of the maltodextrin molecules. The adsorption kinetics and sorption isotherm curves confirmed the increase in the hygroscopicity of maltodextrins with higher degrees of polymerization. The size of the maltodextrin chains influenced the release and protection of the encapsulated lime essential oil. Finally, the maltodextrin polymerization degree can be considered a parameter that will influence the physicochemical properties of microencapsulated food. Copyright © 2017 Elsevier Ltd. All rights reserved.

Mechanism of drug release from silica-gelatin aerogel-Relationship between matrix structure and release kinetics.

PubMed

Veres, Péter; Kéri, Mónika; Bányai, István; Lázár, István; Fábián, István; Domingo, Concepción; Kalmár, József

2017-04-01

Specific features of a silica-gelatin aerogel (3 wt.% gelatin content) in relation to drug delivery has been studied. It was confirmed that the release of both ibuprofen (IBU) and ketoprofen (KET) is about tenfold faster from loaded silica-gelatin aerogel than from pure silica aerogel, although the two matrices are structurally very similar. The main goal of the study was to understand the mechanistic background of the striking difference between the delivery properties of these closely related porous materials. Hydrated and dispersed silica-gelatin aerogel has been characterized by NMR cryoporometry, diffusiometry and relaxometry. The pore structure of the silica aerogel remains intact when it disintegrates in water. In contrast, dispersed silica-gelatin aerogel develops a strong hydration sphere, which reshapes the pore walls and deforms the pore structure. The drug release kinetics was studied on a few minutes time scale with 1s time resolution. Simultaneous evaluation of all relevant kinetic and structural information confirmed that strong hydration of the silica-gelatin skeleton facilitates the rapid desorption and dissolution of the drugs from the loaded aerogel. Such a driving force is not operative in pure silica aerogels. Copyright © 2017 Elsevier B.V. All rights reserved.

Coordination responsive tellurium-containing multilayer film for controlled delivery.

PubMed

Cao, Wei; Wang, Lu; Xu, Huaping

2015-03-28

A coordination-responsive tellurium containing film was fabricated for controlled release. The coordination chemistry between telluride molecules and cisplatin was utilized for the loading of cisplatin, while competitive ligands were used for triggered release. This work could enrich the coordination responsive system and further tune the release kinetics of cisplatin.

Silicon Impurity Release and Surface Transformation of TiO2 Anatase and Rutile Nanoparticles in Water Environments

EPA Science Inventory

Surface transformation can affect the stability, reactivity, and toxicity of titanium dioxide (TiO2) nanoparticles (NPs) when released to water environments. Herein, we investigated the release kinetics of Si impurity frequently introduced during NP synthesis and the resulting ef...

Chitosan nanoparticles as a modified diclofenac drug release system

NASA Astrophysics Data System (ADS)

Duarte Junior, Anivaldo Pereira; Tavares, Eraldo José Madureira; Alves, Taís Vanessa Gabbay; de Moura, Márcia Regina; da Costa, Carlos Emmerson Ferreira; Silva Júnior, José Otávio Carréra; Ribeiro Costa, Roseane Maria

2017-08-01

This study evaluated a modified nanostructured release system employing diclofenac as a drug model. Biodegradable chitosan nanoparticles were prepared with chitosan concentrations between 0.5 and 0.8% ( w/ v) by template polymerization method using methacrylic acid in aqueous solution. Chitosan-poly(methacrylic acid) (CS-PMAA) nanoparticles showed uniform size around 50-100 nm, homogeneous morphology, and spherical shape. Raw material and chitosan nanoparticles were characterized by thermal analysis, Fourier transform infrared spectroscopy (FT-IR), and transmission electron microscopy (TEM), confirming the interaction between chitosan and methacrylic acid during nanoparticles preparation. Diclofenac sorption on the chitosan nanoparticles surface was achieved by incubation in water/ethanol (1:1) drug solution in concentrations of 0.5 and 0.8 mg/mL. The diclofenac amount sorbed per gram of CS-PMAA nanoparticles, when in a 0.5 mg/mL sodium diclofenac solution, was as follows: 12.93, 15, 20.87, and 29.63 mg/g for CS-PMAA nanoparticles 0.5, 0.6, 0.7, and 0.8% ( w/ v), respectively. When a 0.8 mg/mL sodium diclofenac solution was used, higher sorption efficiencies were obtained: For CS-PMAA nanoparticles with chitosan concentrations of 0.5, 0.6, 0.7, and 0.8% ( w/ v), the sorption efficiencies were 33.39, 49.58, 55.23, and 67.2 mg/g, respectively. Diclofenac sorption kinetics followed a second-order kinetics. Drug release from nanoparticles occurred in a period of up to 48 h and obeyed Korsmeyer-Peppas model, which was characterized mainly by Fickian diffusion transport. [Figure not available: see fulltext.

Novel mechanism of antibodies to hepatitis B virus in blocking viral particle release from cells.

PubMed

Neumann, Avidan U; Phillips, Sandra; Levine, Idit; Ijaz, Samreen; Dahari, Harel; Eren, Rachel; Dagan, Shlomo; Naoumov, Nikolai V

2010-09-01

Antibodies are thought to exert antiviral activities by blocking viral entry into cells and/or accelerating viral clearance from circulation. In particular, antibodies to hepatitis B virus (HBV) surface antigen (HBsAg) confer protection, by binding circulating virus. Here, we used mathematical modeling to gain information about viral dynamics during and after single or multiple infusions of a combination of two human monoclonal anti-HBs (HepeX-B) antibodies in patients with chronic hepatitis B. The antibody HBV-17 recognizes a conformational epitope, whereas antibody HBV-19 recognizes a linear epitope on the HBsAg. The kinetic profiles of the decline of serum HBV DNA and HBsAg revealed partial blocking of virion release from infected cells as a new antiviral mechanism, in addition to acceleration of HBV clearance from the circulation. We then replicated this approach in vitro, using cells secreting HBsAg, and compared the prediction of the mathematical modeling obtained from the in vivo kinetics. In vitro, HepeX-B treatment of HBsAg-producing cells showed cellular uptake of antibodies, resulting in intracellular accumulation of viral particles. Blocking of HBsAg secretion also continued after HepeX-B was removed from the cell culture supernatants. These results identify a novel antiviral mechanism of antibodies to HBsAg (anti-HBs) involving prolonged blocking of the HBV and HBsAg subviral particles release from infected cells. This may have implications in designing new therapies for patients with chronic HBV infection and may also be relevant in other viral infections.

Mixing and non-equilibrium chemical reaction in a compressible mixing layer. M.S. Thesis Final Report

NASA Technical Reports Server (NTRS)

Steinberger, Craig J.

1991-01-01

The effects of compressibility, chemical reaction exothermicity, and non-equilibrium chemical modeling in a reacting plane mixing layer were investigated by means of two dimensional direct numerical simulations. The chemical reaction was irreversible and second order of the type A + B yields Products + Heat. The general governing fluid equations of a compressible reacting flow field were solved by means of high order finite difference methods. Physical effects were then determined by examining the response of the mixing layer to variation of the relevant non-dimensionalized parameters. The simulations show that increased compressibility generally results in a suppressed mixing, and consequently a reduced chemical reaction conversion rate. Reaction heat release was found to enhance mixing at the initial stages of the layer growth, but had a stabilizing effect at later times. The increased stability manifested itself in the suppression or delay of the formation of large coherent structures within the flow. Calculations were performed for a constant rate chemical kinetics model and an Arrhenius type kinetic prototype. The choice of the model was shown to have an effect on the development of the flow. The Arrhenius model caused a greater temperature increase due to reaction than the constant kinetic model. This had the same effect as increasing the exothermicity of the reaction. Localized flame quenching was also observed when the Zeldovich number was relatively large.

Release and Decay Kinetics of Copeptin vs AVP in Response to Osmotic Alterations in Healthy Volunteers.

PubMed

Fenske, Wiebke K; Schnyder, Ingeborg; Koch, Gilbert; Walti, Carla; Pfister, Marc; Kopp, Peter; Fassnacht, Martin; Strauss, Konrad; Christ-Crain, Mirjam

2018-02-01

Copeptin is the C-terminal fragment of the arginine vasopressin (AVP) prohormone whose measurement is more robust than that of AVP. Similar release and clearance characteristics have been suggested promoting copeptin as a surrogate marker. To characterize the physiology of osmotically regulated copeptin release and its half-life in direct comparison with plasma AVP. Ninety-one healthy volunteers underwent a standardized three-phase test protocol including (1) osmotic stimulation into the hypertonic range by hypertonic-saline infusion followed by osmotic suppression via (2) oral water load and (3) subsequent glucose infusion. Plasma copeptin, AVP, serum sodium, and osmolality levels were measured in regular intervals. In phase 1, an increase in median osmotic pressure [289 (286; 291) to 311 (309; 314) mOsm/kg H2O] caused similar release kinetics of plasma copeptin [4 (3.1; 6) to 29.3 (18.6; 48.2) pmol/L] and AVP [1 (0.7; 1.6) to 10.3 (6.8; 18.8) pg/mL]. Subsequent osmotic suppression to 298 (295; 301) mOsm/kg at the end of phase 3 revealed markedly different decay kinetics between both peptides-an estimated initial half-life of copeptin being approximately 2 times longer than that of AVP (26 vs 12 minutes). Copeptin is released in equimolar amounts with AVP in response to osmotic stimulation, suggesting its high potential as an AVP surrogate for differentiation of osmotic disorders. Furthermore, we here describe the decay kinetics of copeptin in response to osmotic depression enabling to identify a half-life for copeptin in direct comparison with AVP. Copyright © 2017 Endocrine Society

Combustion-acoustic stability analysis for premixed gas turbine combustors

NASA Technical Reports Server (NTRS)

Darling, Douglas; Radhakrishnan, Krishnan; Oyediran, Ayo; Cowan, Lizabeth

1995-01-01

Lean, prevaporized, premixed combustors are susceptible to combustion-acoustic instabilities. A model was developed to predict eigenvalues of axial modes for combustion-acoustic interactions in a premixed combustor. This work extends previous work by including variable area and detailed chemical kinetics mechanisms, using the code LSENS. Thus the acoustic equations could be integrated through the flame zone. Linear perturbations were made of the continuity, momentum, energy, chemical species, and state equations. The qualitative accuracy of our approach was checked by examining its predictions for various unsteady heat release rate models. Perturbations in fuel flow rate are currently being added to the model.

Effects of membrane composition on release of model hydrophilic compound from osmotic delivery systems.

PubMed

Ozdemir, N; Ozalp, Y; Ozkan, Y

2000-01-01

In this study, the effects of surface-active agents in different types and concentrations, added into the coating solution, on release of model hydrophilic compound have been examined. For this purpose, the tablets, prepared with the use of methylene blue as a model substance, were coated by spray coating technique with cellulose acetate solution containing polyethylene glycol 400 as a plasticizer. In addition, cetylpyridinium chloride as cationic surface-active agent and sodium lauryl sulphate as anionic surface-active agent were added into coating solution in different concentrations. After creating a delivery orifice by a microdrill on the tablets, release of model hydrophilic compound was tested by the USP paddle method. The data obtained were evaluated according to the different kinetics and the mechanism of release from the preparations was examined. The surface properties of the coating material were investigated by scanning electron microscope taken before and after the contact with medium fluid, as well as the mechanical properties by tensile tests. In conclusion, it has been found that the cationic surface active agent, cetylpyridinium chloride reduced the lag time, observed during the release of model hydrophilic compound, as a result of its enhancing effect on wettability of tablets by reducing the contact angle between the medium fluid and the coating material. On the other hand, the anionic surface active agent, sodium lauryl sulphate has been inactivated possibly due to the interaction with model hydrophilic compound that has cationic properties and/or substances contained in membrane composition; thus, the lag time has not decreased and furthermore, a significant decrease in the delivery rate of model hydrophilic compound has been observed.

Sorption and Release of Organics by Primary, Anaerobic, and Aerobic Activated Sludge Mixed with Raw Municipal Wastewater

PubMed Central

Modin, Oskar; Saheb Alam, Soroush; Persson, Frank; Wilén, Britt-Marie

2015-01-01

New activated sludge processes that utilize sorption as a major mechanism for organics removal are being developed to maximize energy recovery from wastewater organics, or as enhanced primary treatment technologies. To model and optimize sorption-based activated sludge processes, further knowledge about sorption of organics onto sludge is needed. This study compared primary-, anaerobic-, and aerobic activated sludge as sorbents, determined sorption capacity and kinetics, and investigated some characteristics of the organics being sorbed. Batch sorption assays were carried out without aeration at a mixing velocity of 200 rpm. Only aerobic activated sludge showed net sorption of organics. Sorption of dissolved organics occurred by a near-instantaneous sorption event followed by a slower process that obeyed 1st order kinetics. Sorption of particulates also followed 1st order kinetics but there was no instantaneous sorption event; instead there was a release of particles upon mixing. The 5-min sorption capacity of activated sludge was 6.5±10.8 mg total organic carbon (TOC) per g volatile suspend solids (VSS) for particulate organics and 5.0±4.7 mgTOC/gVSS for dissolved organics. The observed instantaneous sorption appeared to be mainly due to organics larger than 20 kDa in size being sorbed, although molecules with a size of about 200 Da with strong UV absorbance at 215–230 nm were also rapidly removed. PMID:25768429

A Drug-Eluting Contact Lens

PubMed Central

Ciolino, Joseph B.; Hoare, Todd R.; Iwata, Naomi G.; Behlau, Irmgard; Dohlman, Claes H.; Langer, Robert; Kohane, Daniel S.

2014-01-01

Purpose To formulate and characterize a drug-eluting contact lens designed to provide extended, controlled release of a drug. Methods Prototype contact lenses were created by coating PLGA (poly[lactic-co-glycolic acid]) films containing test compounds with pHEMA (poly[hydroxyethyl methacrylate]) by ultraviolet light polymerization. The films, containing encapsulated fluorescein or ciprofloxacin, were characterized by scanning electron microscopy. Release studies were conducted in phosphate-buffered saline at 37°C with continuous shaking. Ciprofloxacin eluted from the contact lens was studied in an antimicrobial assay to verify antimicrobial effectiveness. Results After a brief and minimal initial burst, the prototype contact lenses demonstrated controlled release of the molecules studied, with zero-order release kinetics under infinite sink conditions for over 4 weeks. The rate of drug release was controlled by changing either the ratio of drug to PLGA or the molecular mass of the PLGA used. Both the PLGA and the pHEMA affected release kinetics. Ciprofloxacin released from the contact lenses inhibited ciprofloxacin-sensitive Staphylococcus aureus at all time-points tested. Conclusions A prototype contact lens for sustained drug release consisting of a thin drug-PLGA film coated with pHEMA could be used as a platform for ocular drug delivery with widespread therapeutic applications. PMID:19136709

Sensitivity of Combustion-Acoustic Instabilities to Boundary Conditions for Premixed Gas Turbine Combustors

NASA Technical Reports Server (NTRS)

Darling, Douglas; Radhakrishnan, Krishnan; Oyediran, Ayo

1995-01-01

Premixed combustors, which are being considered for low NOx engines, are susceptible to instabilities due to feedback between pressure perturbations and combustion. This feedback can cause damaging mechanical vibrations of the system as well as degrade the emissions characteristics and combustion efficiency. In a lean combustor instabilities can also lead to blowout. A model was developed to perform linear combustion-acoustic stability analysis using detailed chemical kinetic mechanisms. The Lewis Kinetics and Sensitivity Analysis Code, LSENS, was used to calculate the sensitivities of the heat release rate to perturbations in density and temperature. In the present work, an assumption was made that the mean flow velocity was small relative to the speed of sound. Results of this model showed the regions of growth of perturbations to be most sensitive to the reflectivity of the boundary when reflectivities were close to unity.

Comparative evaluation of thermal oxidative decomposition for oil-plant residues via thermogravimetric analysis: Thermal conversion characteristics, kinetics, and thermodynamics.

PubMed

Chen, Jianbiao; Wang, Yanhong; Lang, Xuemei; Ren, Xiu'e; Fan, Shuanshi

2017-11-01

Thermal oxidative decomposition characteristics, kinetics, and thermodynamics of rape straw (RS), rapeseed meal (RM), camellia seed shell (CS), and camellia seed meal (CM) were evaluated via thermogravimetric analysis (TGA). TG-DTG-DSC curves demonstrated that the combustion of oil-plant residues proceeded in three stages, including dehydration, release and combustion of organic volatiles, and chars oxidation. As revealed by combustion characteristic parameters, the ignition, burnout, and comprehensive combustion performance of residues were quite distinct from each other, and were improved by increasing heating rate. The kinetic parameters were determined by Coats-Redfern approach. The results showed that the most possible combustion mechanisms were order reaction models. The existence of kinetic compensation effect was clearly observed. The thermodynamic parameters (ΔH, ΔG, ΔS) at peak temperatures were calculated through the activated complex theory. With the combustion proceeding, the variation trends of ΔH, ΔG, and ΔS for RS (RM) similar to those for CS (CM). Copyright © 2017 Elsevier Ltd. All rights reserved.

Computational study of sodium magnesium hydride for hydrogen storage applications

NASA Astrophysics Data System (ADS)

Soto Valle, Fernando Antonio

Hydrogen offers considerable potential benefits as an energy carrier. However, safe and convenient storage of hydrogen is one of the biggest challenges to be resolved in the near future. Sodium magnesium hydride (NaMgH 3) has attracted attention as a hydrogen storage material due to its light weight and high volumetric hydrogen density of 88 kg/m3. Despite the advantages, hydrogen release in this material occurs at approximately 670 K, which is well above the operable range for on-board hydrogen storage applications. In this regard, hydrogen release may be facilitated by substitution doping of transition-metals. This dissertation describes first-principles computational methods that enable an examination of the hydrogen storage properties of NaMgH3. The novel contribution of this dissertation includes a combination of crystal, supercell, and surface slab calculations that provides new and relevant insights about the thermodynamic and kinetic properties of NaMgH3. First-principles calculations on the pristine crystal structure provide a starting reference point for the study of this material as a hydrogen storage material. To the best of our knowledge, it is reported for the first time that a 25% mol doping concentration of Ti, V, Cu, and Zn dopants reduce the reaction enthalpy of hydrogen release for NaMgH3. The largest decrease in the DeltaH(298 K) value corresponds to the Zn-doped model (67.97 kJ/(mol H2)). Based on cohesive energy calculations, it is reported that at the 6.25% mol doping concentration, Ti and Zn dopants are the only transition metals that destabilize the NaMgH3 hydride. In terms of hydrogen removal energy, it is quantified that the energy cost to remove a single H from the Ti-doped supercell model is 0.76 eV, which is lower with respect to the pristine model and other prototypical hydrogen storage materials. From the calculation of electronic properties such as density of states, electron density difference, and charge population analysis schemes it is shown that the effectiveness of these two dopants is due to the modified chemical bonding induce by the overlap of d orbitals. For the surface slab calculations, a key finding is that the preferred layer for the simultaneous substitution of Ti and Zn dopants at two different Na sites is the outermost layer with substitution energy values of -5.27 eV and -5.24 eV, respectively. The kinetic barrier for hydrogen desorption from the (001) surface is studied using DFT calculations, LST/QST, and NEB methods. We find that for the pristine model, the direct recombination of a H 2 molecule has a kinetic barrier of 1.16 eV. More importantly, we find that the calculated kinetic barrier of H2 desorption when the (001) surface is co-doped with Ti and Zn is 0.42 eV. These results show that the combined use of a Ti dopant and a Zn dopant is the best mix for reducing the energy barrier to release hydrogen from the (001) NaMgH3 surface.

Applications of cyclodextrins in medical textiles - review.

PubMed

Radu, Cezar-Doru; Parteni, Oana; Ochiuz, Lacramioara

2016-02-28

This paper presents data on the general properties and complexing ability of cyclodextrins and assessment methods (phase solubility, DSC tests and X-ray diffraction, FTIR spectra, analytical method). It focuses on the formation of drug deposits on the surface of a textile underlayer, using a cyclodextrin compound favoring the inclusion of a drug/active principle and its release onto the dermis of patients suffering from skin disorders, or for protection against insects. Moreover, it presents the kinetics, duration, diffusion flow and release media of the cyclodextrin drug for in vitro studies, as well as the release modeling of the active principle. The information focuses on therapies: antibacterial, anti-allergic, antifungal, chronic venous insufficiency, psoriasis and protection against insects. The pharmacodynamic agents/active ingredients used on cotton, woolen and synthetic textile fabrics are presented. Copyright © 2016 Elsevier B.V. All rights reserved.

Spectroscopic and chemical-kinetic analysis of the phases of HCCI autoignition and combustion for single- and two-stage ignition fuels

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

Hwang, Wontae; Dec, John; Sjoeberg, Magnus

The temporal phases of autoignition and combustion in an HCCI engine have been investigated in both an all-metal engine and a matching optical engine. Gasoline, a primary reference fuel mixture (PRF80), and several representative real-fuel constituents were examined. Only PRF80, which is a two-stage ignition fuel, exhibited a ''cool-flame'' low-temperature heat-release (LTHR) phase. For all fuels, slow exothermic reactions occurring at intermediate temperatures raised the charge temperature to the hot-ignition point. In addition to the amount of LTHR, differences in this intermediate-temperature heat-release (ITHR) phase affect the fuel ignition quality. Chemiluminescence images of iso-octane show a weak and uniform lightmore » emission during this phase. This is followed by the main high-temperature heat-release (HTHR) phase. Finally, a ''burnout'' phase was observed, with very weak uniform emission and near-zero heat-release rate (HRR). To better understand these combustion phases, chemiluminescence spectroscopy and chemical-kinetic analysis were applied for the single-stage ignition fuel, iso-octane, and the two-stage fuel, PRF80. For both fuels, the spectrum obtained during the ITHR phase was dominated by formaldehyde chemiluminescence. This was similar to the LTHR spectrum of PRF80, but the emission intensity and the temperature were much higher, indicating differences between the ITHR and LTHR phases. Chemical-kinetic modeling clarified the differences and similarities between the LTHR and ITHR phases and the cause of the enhanced ITHR with PRF80. The HTHR spectra for both fuels were dominated by a broad CO continuum with some contribution from bands of HCO, CH, and OH. The modeling showed that the CO+ O{yields}CO{sub 2}+h{nu} reaction responsible for the CO continuum emission tracks the HTHR well, explaining the strong correlation observed experimentally between the total chemiluminescence and HRR during the HTHR phase. It also showed that the CO continuum does not contribute to the ITHR and LTHR chemiluminescence. Bands of H{sub 2}O and O{sub 2} in the red and IR regions were also detected during the HTHR, which the data indicated were most likely due to thermal excitation. The very weak light emission in the ''burnout'' phase also appeared to be thermal emission from H{sub 2}O and O{sub 2}. (author)« less

The Stability of Silver Nanoparticles in a Model of Pulmonary Surfactant

PubMed Central

Fen, Leo Bey; Chen, Shu; Kyo, Yoshihiko; Herpoldt, Karla-Luise; Terrill, Nicholas J.; Dunlop, Iain E.; McPhail, David S.; Shaffer, Milo S.; Schwander, Stephan; Gow, Andrew; Zhang, Junfeng (Jim); Chung, Kian Fan; Tetley, Teresa D.; Porter, Alexandra E.; Ryan, Mary P.

2013-01-01

The growing use of silver nanoparticles (AgNPs) in consumer products has raised concerns about their potential impact on the environment and human health. Whether AgNPs dissolve and release Ag+ ions, or coarsen to form large aggregates, is critical in determining their potential toxicity. In this work, the stability of AgNPs in dipalmitoylphosphatidylcholine (DPPC), the major component of pulmonary surfactant, was investigated as a function of pH. Spherical, citrate-capped AgNPs with average diameters of 14 ± 1.6 nm (n=200) were prepared by a chemical bath reduction. The kinetics of Ag+ ion release was strongly pH-dependent. After 14 days of incubation in sodium perchlorate (NaClO4) or perchloric acid (HClO4) solutions, the total fraction of AgNPs dissolved varied from ~10 % at pH 3, to ~2 % at pH 5, with negligible dissolution at pH 7. A decrease in pH from 7 to 3 also promoted particle aggregation and coarsening. DPPC (100 mg.L−1) delayed the release of Ag+ ions, but did not significantly alter the total amount of Ag+ released after two weeks. In addition, DPPC improved the dispersion of the AgNPs and inhibited aggregation and coarsening. TEM images revealed that the AgNPs were coated with a DPPC layer serving as a semi-permeable layer. Hence, lung lining fluid, particularly DPPC, can modify the aggregation state and kinetics of Ag+ ion release of inhaled AgNPs in the lung. These observations have important implications for predicting the potential reactivity of AgNPs in the lung and the environment. PMID:23988335

Release kinetics of vanadium from vanadium titano-magnetite: The effects of pH, dissolved oxygen, temperature and foreign ions.

PubMed

Hu, Xingyun; Yue, Yuyan; Peng, Xianjia

2018-02-01

As part of a broader study of the environmental geochemistry behavior of vanadium (V), the release kinetics of V from the dissolution of natural vanadium titano-magnetite under environmentally relevant conditions was investigated. In both the acidic and basic domains, the V release rate was found to be proportional to fractional powers of hydrogen ion and dissolved oxygen activities. The dependence of the rate on dissolved oxygen can also be described in terms of the Langmuir adsorption model. The empirical rate equation is given by: r [Formula: see text] where, α=0.099-0.265, k'=3.2×10 -6 -1.7×10 -5 , K=2.7×10 4 -3.9×10 4 mol/L in acid solution (pH4.1), and α=-0.494-(-0.527), k'=2.0×10 4 -2.5×10 -11 , and K=4.1×10 3 -6.5×10 3 mol/L in basic solution (pH8.8) at 20°C. Based on the effect of temperature on the release rate of V, the activation energies of minerals at pH8.8 were determined to be 148-235kJ/mol, suggesting that the dissolution of vanadium titano-magnetite is a surface-controlled process. The presence of Na + , Ca 2+ , Mg 2+ , K + , NO 3 - , Cl - , SO 4 2- and CO 3 2- was found to accelerate the V release rates. This study improves the understanding of both the V pollution risk in some mine areas and the fate of V in the environment. Copyright © 2017. Published by Elsevier B.V.

SNARE-mediated Fusion of Single Proteoliposomes with Tethered Supported Bilayers in a Microfluidic Flow Cell Monitored by Polarized TIRF Microscopy

PubMed Central

Nikolaus, Joerg; Karatekin, Erdem

2016-01-01

In the ubiquitous process of membrane fusion the opening of a fusion pore establishes the first connection between two formerly separate compartments. During neurotransmitter or hormone release via exocytosis, the fusion pore can transiently open and close repeatedly, regulating cargo release kinetics. Pore dynamics also determine the mode of vesicle recycling; irreversible resealing results in transient, "kiss-and-run" fusion, whereas dilation leads to full fusion. To better understand what factors govern pore dynamics, we developed an assay to monitor membrane fusion using polarized total internal reflection fluorescence (TIRF) microscopy with single molecule sensitivity and ~15 msec time resolution in a biochemically well-defined in vitro system. Fusion of fluorescently labeled small unilamellar vesicles containing v-SNARE proteins (v-SUVs) with a planar bilayer bearing t-SNAREs, supported on a soft polymer cushion (t-SBL, t-supported bilayer), is monitored. The assay uses microfluidic flow channels that ensure minimal sample consumption while supplying a constant density of SUVs. Exploiting the rapid signal enhancement upon transfer of lipid labels from the SUV to the SBL during fusion, kinetics of lipid dye transfer is monitored. The sensitivity of TIRF microscopy allows tracking single fluorescent lipid labels, from which lipid diffusivity and SUV size can be deduced for every fusion event. Lipid dye release times can be much longer than expected for unimpeded passage through permanently open pores. Using a model that assumes retardation of lipid release is due to pore flickering, a pore "openness", the fraction of time the pore remains open during fusion, can be estimated. A soluble marker can be encapsulated in the SUVs for simultaneous monitoring of lipid and soluble cargo release. Such measurements indicate some pores may reseal after losing a fraction of the soluble cargo. PMID:27585113

Phosphate release coupled to rotary motion of F1-ATPase

PubMed Central

Okazaki, Kei-ichi; Hummer, Gerhard

2013-01-01

F1-ATPase, the catalytic domain of ATP synthase, synthesizes most of the ATP in living organisms. Running in reverse powered by ATP hydrolysis, this hexameric ring-shaped molecular motor formed by three αβ-dimers creates torque on its central γ-subunit. This reverse operation enables detailed explorations of the mechanochemical coupling mechanisms in experiment and simulation. Here, we use molecular dynamics simulations to construct a first atomistic conformation of the intermediate state following the 40° substep of rotary motion, and to study the timing and molecular mechanism of inorganic phosphate (Pi) release coupled to the rotation. In response to torque-driven rotation of the γ-subunit in the hydrolysis direction, the nucleotide-free αβE interface forming the “empty” E site loosens and singly charged Pi readily escapes to the P loop. By contrast, the interface stays closed with doubly charged Pi. The γ-rotation tightens the ATP-bound αβTP interface, as required for hydrolysis. The calculated rate for the outward release of doubly charged Pi from the αβE interface 120° after ATP hydrolysis closely matches the ∼1-ms functional timescale. Conversely, Pi release from the ADP-bound αβDP interface postulated in earlier models would occur through a kinetically infeasible inward-directed pathway. Our simulations help reconcile conflicting interpretations of single-molecule experiments and crystallographic studies by clarifying the timing of Pi exit, its pathway and kinetics, associated changes in Pi protonation, and changes of the F1-ATPase structure in the 40° substep. Important elements of the molecular mechanism of Pi release emerging from our simulations appear to be conserved in myosin despite the different functional motions. PMID:24062450

Decomposition mechanisms and kinetics of novel energetic molecules BNFF-1 and ANFF-1: quantum-chemical modeling.

PubMed

Tsyshevsky, Roman V; Kuklja, Maija M

2013-07-18

Decomposition mechanisms, activation barriers, Arrhenius parameters, and reaction kinetics of the novel explosive compounds, 3,4-bis(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole (BNFF-1), and 3-(4-amino-1,2,5-oxadiazol-3-yl)-4-(4-nitro-1,2,5-oxadiazol-3-yl)-1,2,5-oxadiazole (ANFF-1) were explored by means of density functional theory with a range of functionals combined with variational transition state theory. BNFF-1 and ANFF-1 were recently suggested to be good candidates for insensitive high energy density materials. Our modeling reveals that the decomposition initiation in both BNFF-1 and ANFF-1 molecules is triggered by ring cleavage reactions while the further process is defined by a competition between two major pathways, the fast C-NO₂ homolysis and slow nitro-nitrite isomerization releasing NO. We discuss insights on design of new energetic materials with targeted properties gained from our modeling.

The controlled release of tilmicosin from silica nanoparticles.

PubMed

Song, Meirong; Li, Yanyan; Fai, Cailing; Cui, Shumin; Cui, Baoan

2011-06-01

The aim of this study was to use silica nanoparticles as the carrier for controlled release of tilmicosin. Tilmicosin was selected as a drug model molecule because it has a lengthy elimination half-life and a high concentration in milk after subcutaneous administration. Three samples of tilmicosin-loaded silica nanoparticles were prepared with different drug-loading weight. The drug-loading weight in three samples, as measured by thermal gravimetric analysis, was 29%, 42%, and 64%, respectively. With increased drug-loading weight, the average diameter of the drug-loaded silica nanoparticles was increased from 13.4 to 25.7 nm, and the zeta potential changed from-30.62 to-6.78 mV, indicating that the stability of the drug-loaded particles in the aqueous solution decreases as drug-loading weight increases. In vitro release studies in phosphate-buffered saline showed the sample with 29% drug loading had a slow and sustained drug release, reaching 44% after 72 h. The release rate rose with increased drug-loading weight; therefore, the release of tilmicosin from silica nanoparticles was well-controlled by adjusting the drug loading. Finally, kinetics analysis suggested that drug released from silica nanoparticles was mainly a diffusion-controlled process.

Surface Modifications of Titanium Implants by Multilayer Bioactive Coatings with Drug Delivery Potential: Antimicrobial, Biological, and Drug Release Studies

NASA Astrophysics Data System (ADS)

Ordikhani, Farideh; Zustiak, Silviya Petrova; Simchi, Abdolreza

2016-04-01

Recent strategies to locally deliver antimicrobial agents to combat implant-associated infections—one of the most common complications in orthopedic surgery—are gaining interest. However, achieving a controlled release profile over a desired time frame remains a challenge. In this study, we present an innovative multifactorial approach to combat infections which comprises a multilayer chitosan/bioactive glass/vancomycin nanocomposite coating with an osteoblastic potential and a drug delivery capacity. The bioactive drug-eluting coating was prepared on the surface of titanium foils by a multistep electrophoretic deposition technique. The adopted deposition strategy allowed for a high antibiotic loading of 1038.4 ± 40.2 µg/cm2. The nanocomposite coating exhibited a suppressed burst release with a prolonged sustained vancomycin release for up to 6 weeks. Importantly, the drug release profile was linear with respect to time, indicating a zero-order release kinetics. An in vitro bactericidal assay against Staphylococcus aureus confirmed that releasing the drug reduced the risk of bacterial infection. Excellent biocompatibility of the developed coating was also demonstrated by in vitro cell studies with a model MG-63 osteoblast cell line.

Formulation and evaluation of diclofenac controlled release matrix tablets made of HPMC and Poloxamer 188 polymer: An assessment on mechanism of drug release.

PubMed

Al-Hanbali, Othman A; Hamed, Rania; Arafat, Mosab; Bakkour, Youssef; Al-Matubsi, Hisham; Mansour, Randa; Al-Bataineh, Yazan; Aldhoun, Mohammad; Sarfraz, Muhammad; Dardas, Abdel Khaleq Yousef

2018-01-01

In this study, hydrophilic hydroxypropyl methylcellulose matrices with various concentrations of Poloxamer 188 were used in the development of oral controlled release tablets containing diclofenac sodium. Four formulations of hydrophilic matrix tablets containing 16.7% w/w HPMC and 0, 6.7, 16.7 and 25.0% w/w Poloxamer 188, respectively, were developed. Tablets were prepared by direct compression and characterized for diameter, hardness, thickness, weight and uniformity of content. The influence of various blends of hydroxypropyl methylcellulose and Poloxamer 188 on the in vitro dissolution profile and mechanism of drug release of was investigated. In the four formulations, the rate of drug release decreased with increasing the concentration of Poloxamer 188 at the initial dissolution stages due to the increase in the apparent viscosity of the gel diffusion layer. However, in the late dissolution stages, the rate of drug release increased with increasing Poloxamer 188 concentration due to the increase in wettability and dissolution of the matrix. The kinetic of drug release from the tablets followed non-Fickian mechanism, as predicted by Korsmeyer-Peppas model, which involves diffusion through the gel layer and erosion of the matrix system.

Nanosize effect of clay mineral nanoparticles on the drug diffusion processes in polyurethane nanocomposite hydrogels

NASA Astrophysics Data System (ADS)

Miotke, M.; Strankowska, J.; Kwela, J.; Strankowski, M.; Piszczyk, Ł.; Józefowicz, M.; Gazda, M.

2017-09-01

Studies of swelling and release of naproxen sodium (NAP) solution by polyurethane nanocomposite hydrogels containing Cloisite® 30B (organically modified montmorillonite (OMMT)) have been performed. Polyurethane nanocomposite hydrogels are hybrid, nontoxic biomaterials with unique swelling and release properties in comparison with unmodified hydrogels. These features enable to use nanocomposite hydrogels as a modern wound dressing. The presence of nanoparticles significantly improves the swelling. On the other hand, their presence hinders drug diffusion from polymer matrix and consequently causes delay of the drug release. The kinetics of swelling and release were carefully analyzed using the Korsmeyer-Peppas and the modified Hopfenberg models. The models were fitted to precise experimental data allowing accurate quantitative and qualitative analysis. We observed that 0.5% admixture of nanoparticles (Cloisite® 30B) is the best concentration for hydrogel swelling properties. The release process was studied using fluorescence excitation spectra of NAP. Furthermore, we studied swelling hysteresis; polymer chains have not been destroyed after the swelling and part of swelled solution with active substances which remained absorbed in the polymer matrix after the drying process. We have found that the amount of solution with NAP remained in the nanocomposite matrix is greater than in pure hydrogel, as a consequence of NAP-OMMT interactions (nanosize effect).

Tritium release from SS316 under vacuum condition

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

Torikai, Y.; Penzhorn, R.D.

The plasma facing surface of the ITER vacuum vessel, partly made of low carbon austenitic stainless steel type 316L, will incorporate tritium during machine operation. In this paper the kinetics of tritium release from stainless steel type 316 into vacuum and into a noble gas stream are compared and modelled. Type 316 stainless steel specimens loaded with tritium either by exposure to 1.2 kPa HT at 573 K or submersion into liquid HTO at 298 K showed characteristic thin surface layers trapping tritium in concentrations far higher than those determined in the bulk. The evolution of the tritium depth profilemore » in the bulk during heating under vacuum was non-discernible from that of tritium liberated into a stream of argon. Only the relative amount of the two released tritium-species, i.e. HT or HTO, was different. Temperature-dependent depth profiles could be predicted with a one-dimensional diffusion model. Diffusion coefficients derived from fitting of the tritium release into an evacuated vessel or a stream of argon were found to be (1.4 ± 1.0)*10{sup -7} and (1.3 ± 0.9)*10{sup -9} cm{sup 2}/s at 573 and 423 K, respectively. Polished surfaces on type SS316 stainless steel inhibit considerably the thermal release rate of tritium.« less

Timolol maleate release from hyaluronic acid-containing model silicone hydrogel contact lens materials.

PubMed

Korogiannaki, Myrto; Guidi, Giuliano; Jones, Lyndon; Sheardown, Heather

2015-09-01

This study was designed to assess the impact of a releasable wetting agent, such as hyaluronic acid (HA), on the release profile of timolol maleate (TM) from model silicone hydrogel contact lens materials. Polyvinylpyrrolidone (PVP) was used as an alternative wetting agent for comparison. The model lenses consisted of a hydrophilic monomer, either 2-hydroxyethyl methacrylate or N,N-dimethylacrylamide and a hydrophobic silicone monomer of methacryloxypropyltris (trimethylsiloxy) silane. The loading of the wetting and the therapeutic agent occurred during the synthesis of the silicone hydrogels through the method of direct entrapment. The developed materials were characterized by minimal changes in the water uptake, while lower molecular weight of HA improved their surface wettability. The transparency of the examined silicone hydrogels was found to be affected by the miscibility of the wetting agent in the prepolymer mixture as well as the composition of the developed silicone hydrogels. Sustained release of TM from 4 to 14 days was observed, with the drug transport occurring presumably through the hydrophilic domains of the silicone hydrogels. The release profile was strongly dependent on the hydrophilic monomer composition, the distribution of hydrophobic (silane) domains, and the affinity of the therapeutic agent for the silicone hydrogel matrix. Noncovalent entrapment of the wetting agent did not change the in vitro release duration and kinetics of TM, however the drug release profile was found to be controlled by the simultaneous release of TM and HA or PVP. In the case of HA, depending on the HA:drug ratio, the release rate was decreased and controlled by the release of HA, likely due to electrostatic interactions between protonated TM and anionic HA. Overall, partitioning of the drug within the hydrophilic domains of the silicone hydrogels as well as interactions with the wetting agent determined the drug release profile. © The Author(s) 2015.

Dissolution kinetics of a lunar glass simulant at 25 degrees C: the effect of pH and organic acids

NASA Technical Reports Server (NTRS)

Eick, M. J.; Grossl, P. R.; Golden, D. C.; Sparks, D. L.; Ming, D. W.

1996-01-01

The dissolution kinetics of a simulated lunar glass were examined at pH 3, 5, and 7. Additionally, the pH 7 experiments were conducted in the presence of citric and oxalic acid at concentrations of 2 and 20 mM. The organic acids were buffered at pH 7 to examine the effect of each molecule in their dissociated form. At pH 3, 5, and 7, the dissolution of the synthetic lunar glass was observed to proceed via a two-stage process. The first stage involved the parabolic release of Ca, Mg, Al, and Fe, and the linear release of Si. Dissolution was incongruent, creating a leached layer rich in Si and Ti which was verified by transmission electron microscopy (TEM). During the second stage the release of Ca, Mg, Al, and Fe was linear. A coupled diffusion/surface dissolution model was proposed for dissolution of the simulated lunar glass at pH 3, 5, and 7. During the first stage the initial release of mobile cations (i.e., Ca, Mg, Al, Fe) was limited by diffusion through the surface leached layer of the glass (parabolic release), while Si release was controlled by the hydrolysis of the Si-O-Al bonds at the glass surface (linear release). As dissolution continued, the mobile cations diffused from greater depths within the glass surface. A steady-state was then reached where the diffusion rate across the increased path lengths equalled the Si release rate from the surface. In the presence of the organic acids, the dissolution of the synthetic lunar glass proceeded by a one stage process. The release of Ca, Mg, Al, and Fe followed a parabolic relationship, while the release of Si was linear. The relative reactivity of the organic acids used in the experiments was citrate > oxalate. A thinner leached layer rich in Si/Ti, as compared to the pH experiments, was observed using TEM. Rate data suggest that the chemisorption of the organic anion to the surface silanol groups was responsible for enhanced dissolution in the presence of the organic acids. It is proposed that the increased rate of Si release is responsible for the one stage parabolic release of mobile cations and the relatively thin leached layer compared to experiments at pH 3 and 5.

Formulation of bi-layer matrix tablets of tramadol hydrochloride: Comparison of rate retarding ability of the incorporated hydrophilic polymers.

PubMed

Arif, Hasanul; Al-Masum, Abdullah; Sharmin, Florida; Reza, Selim; Sm Islam, Sm Ashraful

2015-05-01

Bi-layer tablets of tramadol hydrochloride were prepared by direct compression technique. Each tablet contains an instant release layer with a sustained release layer. The instant release layer was found to release the initial dose immediately within minutes. The instant release layer was combined with sustained release matrix made of varying quantity of Methocel K4M, Methocel K15MCR and Carbomer 974P. Bi-layer tablets were evaluated for various physical tests including weight variation, thickness and diameter, hardness and percent friability. Drug release from bi-layer tablet was studied in acidic medium and buffer medium for two and six hours respectively. Sustained release of tramadol hydrochloride was observed with a controlled fashion that was characteristic to the type and extent of polymer used. % Drug release from eight-hour dissolution study was fitted with several kinetic models. Mean dissolution time (MDT) and fractional dissolution values (T25%, T50% and T80%) were also calculated as well, to compare the retarding ability of the polymers. Methocel K15MCR was found to be the most effective in rate retardation of freely water-soluble tramadol hydrochloride compared to Methocel K4M and Capbomer 974P, when incorporated at equal ratio in the formulation.

Influence of poloxamers on the dissolution performance and stability of controlled-release formulations containing Precirol ATO 5.

PubMed

Jannin, V; Pochard, E; Chambin, O

2006-02-17

Lipid excipients are usually used for the development of sustained-release formulations. When used in relatively high quantities, Precirol ATO 5 imparts sustained-release properties to solid oral dosage forms, by forming a lipid matrix. To control or adjust the drug release kinetics from such lipid matrix however, one must often resort to complementary ingredients or techniques. This study investigates the influence of poloxamers (Lutrol) included in lipid matrices composed of glyceryl palmitostearate (Precirol ATO 5) on their dissolution performance and their stability. The addition of these hydrophilic polymers in the lipid matrix increased the amount of theophylline released thanks to the swelling of the hydrophilic polymer and the creation of a porous network into the inert lipid matrix. The grade and the quantity of Lutrol could modulate the extent of drug release. Theophylline was released mainly by the matrix erosion but also by diffusion through the pores as suggested by the Peppas' model. Moreover, the addition of Lutrol enhanced the stability during storage. The theophylline release was quite steady after 6 months in different conditions (temperature and humidity). Thus, the mixture of glyceryl palmitostearate and poloxamers is an approach with many advantages for the development of controlled-release formulations by capsule molding.

Preparation of hollow magnetite microspheres and their applications as drugs carriers

PubMed Central

2012-01-01

Hollow magnetite microspheres have been synthesized by a simple process through a template-free hydrothermal approach. Hollow microspheres were surface modified by coating with a silica nanolayer. Pristine and modified hollow microparticles were characterized by field-emission electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, FT-IR and Raman spectroscopy, and VSM magnetometry. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rhodamine B and methotrexate as model drugs. The loading and release kinetics of both molecules showed a clear pH and temperature dependent profile. Graphical abstract Hollow magnetite microspheres have been synthesized. Load-release experiments with Rhodamine-B as a model drug and with Methotrexate (chemotherapy drug used in treating certain types of cancer) demonstrated the potential applications of these nanostructures in biomedical applications. PMID:22490731

A diels-alder modulated approach to control and sustain the release of dexamethasone and induce osteogenic differentiation of human mesenchymal stem cells

PubMed Central

Koehler, Kenneth C.; Alge, Daniel L.; Anseth, Kristi S.; Bowman, Christopher N.

2013-01-01

We report a new approach to controlled drug release based upon exploiting the dynamic equilibrium that exists between Diels-Alder reactants and products, demonstrating the release of a furan containing dexamethasone peptide (dex-KGPQG-furan) from a maleimide containing hydrogel. Using a reaction-diffusion model, the release kinetics were tuned to achieve sustained concentrations conducive to osteogenic differentiation of human mesenchymal stem cells (hMSCs). Efficacy was first demonstrated in a 2D culture model, in which dexamethasone release induced significant increases in alkaline phosphatase (ALP) activity and mineral deposition in hMSCs compared to a dexamethasone-free treatment. The results were similar to that observed with a soluble dexamethasone treatment. More dramatic differences were observed in 3D culture, where co-encapsulation of a dexamethasone releasing hydrogel depot within an hMSC-laden extracellular matrix mimetic poly(ethylene glycol) hydrogel resulted in a local and robust osteogenic differentiation. ALP activity reached levels that were up to six times higher than the dexamethasone free treatment. Interestingly, at 5 and 10 day time points, the ALP activity exceeded the dexamethasone positive control, suggesting a potential benefit of sustained release in 3D culture. After 21 days, substantial mineralization comparable to the positive control was also observed in the hydrogels. Collectively, these results demonstrate Diels-Alder modulated release as an effective and versatile new platform for controlled drug delivery that may prove especially beneficial for sustaining the release of low molecular weight molecules in hydrogel systems. PMID:23465826

Fission-fragment total kinetic energy and mass yields for neutron-induced fission of 235U and 238U with En =200 keV - 30 MeV

NASA Astrophysics Data System (ADS)

Duke, D. L.; Tovesson, F.; Brys, T.; Geppert-Kleinrath, V.; Hambsch, F.-J.; Laptev, A.; Meharchand, R.; Manning, B.; Mayorov, D.; Meierbachtol, K.; Mosby, S.; Perdue, B.; Richman, D.; Shields, D.; Vidali, M.

2017-09-01

The average Total Kinetic Energy (TKE) release and fission-fragment yields in neutron-induced fission of 235U and 238U was measured using a Frisch-gridded ionization chamber. These observables are important nuclear data quantites that are relevant to applications and for informing the next generation of fission models. The measurements were performed a the Los Alamos Neutron Science Center and cover En = 200 keV - 30 MeV. The double-energy (2E) method was used to determine the fission-fragment yields and two methods of correcting for prompt-neutron emission were explored. The results of this study are correlated mass and TKE data.

Rate of reaction of OH with HNO3

NASA Technical Reports Server (NTRS)

Wine, P. H.; Ravishankara, A. R.; Kreutter, N. M.; Shah, R. C.; Nicovich, J. M.; Thompson, R. L.; Wuebbles, D. J.

1981-01-01

Measurements of the kinetics of the reaction of OH with HNO3, and mechanisms of HNO3 removal from the stratosphere, are reported. Bimolecular rate constants were determined at temperatures between 224 and 366 K by monitoring the concentrations of OH radicals produced by HNO3 photolysis and HNO3 according to their resonance fluorescence and 184.9-nm absorption, respectively. The rate constant measured at 298 K is found to be somewhat faster than previously accepted values, with a negative temperature dependence. Calculations of a one-dimensional transport-kinetic atmospheric model on the basis of the new rate constant indicate reductions in O3 depletion due to chlorofluoromethane release and NOx injection, of magnitudes dependent on the nature of the reaction products.

Some aspects of the damage kinetics at static loading of a heterogeneous solid under the conditions of constrained deformation

NASA Astrophysics Data System (ADS)

Leksovskii, A. M.; Baskin, B. L.; Yakushev, P. N.

2015-12-01

The damaging kinetics of a composite system subjected to static loading, which simulates an inhomogeneous body with microductility, and of D16T-B(43%) composite simulating a quasi-brittle solid is analyzed with the acoustic emission method. By using laser interferometry, it is shown on a model sample that mesocracking may cause a short-term change in the plastic strain rate, which two or more orders of magnitude exceeds the change in the creep rate during the usual supramolecular structure reconfiguration. Whether the object will remain functional or acquire damage of the next scale after being subjected to such local "impact" loading depends on the ability of its immediate environment to absorb released energy.

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

PubMed Central

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

2012-01-01

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

Inorganically modified diatomite as a potential prolonged-release drug carrier.

PubMed

Janićijević, Jelena; Krajišnik, Danina; Calija, Bojan; Dobričić, Vladimir; Daković, Aleksandra; Krstić, Jugoslav; Marković, Marija; Milić, Jela

2014-09-01

Inorganic modification of diatomite was performed with the precipitation product of partially neutralized aluminum sulfate solution at three different mass ratios. The starting and the modified diatomites were characterized by SEM-EDS, FTIR, thermal analysis and zeta potential measurements and evaluated for drug loading capacity in adsorption batch experiments using diclofenac sodium (DS) as a model drug. In vitro drug release studies were performed in phosphate buffer pH6.8 from comprimates containing: the drug adsorbed onto the selected modified diatomite sample (DAMD), physical mixture of the drug with the selected modified diatomite sample (PMDMD) and physical mixture of the drug with the starting diatomite (PMDD). In vivo acute toxicity testing of the modified diatomite samples was performed on mice. High adsorbent loading of the selected modified diatomite sample (~250mg/g in 2h) enabled the preparation of comprimates containing adsorbed DS in the amount near to its therapeutic dose. Drug release studies demonstrated prolonged release of DS over a period of 8h from both DAMD comprimates (18% after 8h) and PMDMD comprimates (45% after 8h). The release kinetics for DAMD and PMDMD comprimates fitted well with Korsmeyer-Peppas and Bhaskar models, indicating that the release mechanism was a combination of non-Fickian diffusion and ion exchange process. Copyright © 2014 Elsevier B.V. All rights reserved.

Biosorption of copper ions from dilute aqueous solutions on base treated rubber (Hevea brasiliensis) leaves powder: kinetics, isotherm, and biosorption mechanisms.

PubMed

Wan Ngah, W S; Hanafiah, M A K M

2008-01-01

The efficiency of sodium hydroxide treated rubber (Hevea brasiliensis) leaves powder (NHBL) for removing copper ions from aqueous solutions has been investigated. The effects of physicochemical parameters on biosorption capacities such as stirring speed, pH, biosorbent dose, initial concentrations of copper, and ionic strength were studied. The biosorption capacities of NHBL increased with increase in pH, stirring speed and copper concentration but decreased with increase in biosorbent dose and ionic strength. The isotherm study indicated that NHBL fitted well with Langmuir model compared to Freundlich and Dubinin-Radushkevich models. The maximum biosorption capacity determined from Langmuir isotherm was 14.97 mg/g at 27 degrees C. The kinetic study revealed that pseudosecond order model fitted well the kinetic data, while Boyd kinetic model indicated that film diffusion was the main rate determining step in biosorption process. Based on surface area analysis, NHBL has low surface area and categorized as macroporous. Fourier transform infrared (FT-IR) analyses revealed that hydroxyl, carboxyl, and amino are the main functional groups involved in the binding of copper ions. Complexation was one of the main mechanisms for the removal of copper ions as indicated by FT-IR spectra. Ion exchange was another possible mechanism since the ratio of adsorbed cations (Cu2+ and H+) to the released cations (Na+, Ca2+, and Mg2+) from NHBL was almost unity. Copper ions bound on NHBL were able to be desorbed at > 99% using 0.05 mol/L HCl, 0.01 mol/L HNO3, and 0.01 mol/L EDTA solutions.

Anti-inflammatory activity of Achillea and Ruscus topical gel on carrageenan-induced paw edema in rats.

PubMed

Maswadeh, Hamzah M; Semreen, Mohammad H; Naddaf, Ahmad R

2006-01-01

The anti-inflammatory activity of Achillea and Ruscus extracts was studied in comparison with diclofenac sodium topical gel (diclosal Emulgel), using the carrageenan induced paw edema model in Albino rats. Gel formulation was prepared containing 6% of each extract in gel base, namely sodium carboxymethylcellulose (NaCMC). The kinetics of drug release from the prepared formulation was studied separately in each case. Results showed that the release follows the Higuchi square root equation. The pharmacological screening revealed that the percent reduction of edema for Achillea extract and Ruscus extract were 48.1% and 18.8%, respectively, while diclosal Emulgel produced 47% reduction of edema.

Encapsulation of Ethylene Gas into Granular Cold-Water-Soluble Starch: Structure and Release Kinetics.

PubMed

Shi, Linfan; Fu, Xiong; Tan, Chin Ping; Huang, Qiang; Zhang, Bin

2017-03-15

Ethylene gas was introduced into granular cold-water-soluble (GCWS) starches using a solid encapsulation method. The morphological and structural properties of the novel inclusion complexes (ICs) were characterized using scanning electron microscopy, X-ray diffractometry, and Raman spectroscopy. The V-type single helix of GCWS starches was formed through controlled gelatinization and ethanol precipitation and was approved to host ethylene gas. The controlled release characteristics of ICs were also investigated at various temperature and relative humidity conditions. Avrami's equation was fitted to understand the release kinetics and showed that the release of ethylene from the ICs was accelerated by increasing temperature or RH and was decelerated by increased degree of amylose polymerization. The IC of Hylon-7 had the highest ethylene concentration (31.8%, w/w) among the five starches, and the IC of normal potato starch showed the best controlled release characteristics. As a renewable and inexpensive material, GCWS starch is a desirable solid encapsulation matrix with potential in agricultural and food applications.

Speciation and Release Kinetics of Cadmium in an Alkaline Paddy Soil Under Various Flooding Periods and Draining Conditions

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

S Khaokaew; R Chaney; G Landrot

2011-12-31

This study determined Cd speciation and release kinetics in a Cd-Zn cocontaminated alkaline paddy soil, under various flooding periods and draining conditions, by employing synchrotron-based techniques, and a stirred-flow kinetic method. Results revealed that varying flooding periods and draining conditions affected Cd speciation and its release kinetics. Linear least-squares fitting (LLSF) of bulk X-ray absorption fine structure (XAFS) spectra of the air-dried, and the 1 day-flooded soil samples, showed that at least 50% of Cd was bound to humic acid. Cadmium carbonates were found as the major species at most flooding periods, while a small amount of cadmium sulfide wasmore » found after the soils were flooded for longer periods. Under all flooding and draining conditions, at least 14 mg/kg Cd was desorbed from the soil after a 2-hour desorption experiment. The results obtained by micro X-ray fluorescence ({mu}-XRF) spectroscopy showed that Cd was less associated with Zn than Ca, in most soil samples. Therefore, it is more likely that Cd and Ca will be present in the same mineral phases rather than Cd and Zn, although the source of these two latter elements may originate from the same surrounding Zn mines in the Mae Sot district.« less

The asparagine-transamidosome from Helicobacter pylori: a dual-kinetic mode in non-discriminating aspartyl-tRNA synthetase safeguards the genetic code

PubMed Central

Fischer, Frédéric; Huot, Jonathan L.; Lorber, Bernard; Diss, Guillaume; Hendrickson, Tamara L.; Becker, Hubert D.; Lapointe, Jacques; Kern, Daniel

2012-01-01

Helicobacter pylori catalyzes Asn-tRNAAsn formation by use of the indirect pathway that involves charging of Asp onto tRNAAsn by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS), followed by conversion of the mischarged Asp into Asn by the GatCAB amidotransferase. We show that the partners of asparaginylation assemble into a dynamic Asn-transamidosome, which uses a different strategy than the Gln-transamidosome to prevent the release of the mischarged aminoacyl-tRNA intermediate. The complex is described by gel-filtration, dynamic light scattering and kinetic measurements. Two strategies for asparaginylation are shown: (i) tRNAAsn binds GatCAB first, allowing aminoacylation and immediate transamidation once ND-AspRS joins the complex; (ii) tRNAAsn is bound by ND-AspRS which releases the Asp-tRNAAsn product much slower than the cognate Asp-tRNAAsp; this kinetic peculiarity allows GatCAB to bind and transamidate Asp-tRNAAsn before its release by the ND-AspRS. These results are discussed in the context of the interrelation between the Asn and Gln-transamidosomes which use the same GatCAB in H. pylori, and shed light on a kinetic mechanism that ensures faithful codon reassignment for Asn. PMID:22362756

The asparagine-transamidosome from Helicobacter pylori: a dual-kinetic mode in non-discriminating aspartyl-tRNA synthetase safeguards the genetic code.

PubMed

Fischer, Frédéric; Huot, Jonathan L; Lorber, Bernard; Diss, Guillaume; Hendrickson, Tamara L; Becker, Hubert D; Lapointe, Jacques; Kern, Daniel

2012-06-01

Helicobacter pylori catalyzes Asn-tRNA(Asn) formation by use of the indirect pathway that involves charging of Asp onto tRNA(Asn) by a non-discriminating aspartyl-tRNA synthetase (ND-AspRS), followed by conversion of the mischarged Asp into Asn by the GatCAB amidotransferase. We show that the partners of asparaginylation assemble into a dynamic Asn-transamidosome, which uses a different strategy than the Gln-transamidosome to prevent the release of the mischarged aminoacyl-tRNA intermediate. The complex is described by gel-filtration, dynamic light scattering and kinetic measurements. Two strategies for asparaginylation are shown: (i) tRNA(Asn) binds GatCAB first, allowing aminoacylation and immediate transamidation once ND-AspRS joins the complex; (ii) tRNA(Asn) is bound by ND-AspRS which releases the Asp-tRNA(Asn) product much slower than the cognate Asp-tRNA(Asp); this kinetic peculiarity allows GatCAB to bind and transamidate Asp-tRNA(Asn) before its release by the ND-AspRS. These results are discussed in the context of the interrelation between the Asn and Gln-transamidosomes which use the same GatCAB in H. pylori, and shed light on a kinetic mechanism that ensures faithful codon reassignment for Asn.

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

Ullah, Ghanim; Demuro, Angelo; Parker, Ian

Amyloid beta (Aβ) oligomers associated with Alzheimer’s disease (AD) form Ca 2+-permeable plasma membrane pores, leading to a disruption of the otherwise well-controlled intracellular calcium (Ca 2+) homeostasis. The resultant up-regulation of intracellular Ca 2+ concentration has detrimental implications for memory formation and cell survival. The gating kinetics and Ca 2+ permeability of Aβ pores are not well understood. We have used computational modeling in conjunction with the ability of optical patch-clamping for massively parallel imaging of Ca 2+ flux through thousands of pores in the cell membrane of Xenopus oocytes to elucidate the kinetic properties of Aβ pores. Themore » fluorescence time-series data from individual pores were idealized and used to develop data-driven Markov chain models for the kinetics of the Aβ pore at different stages of its evolution. Our study provides the first demonstration of developing Markov chain models for ion channel gating that are driven by optical-patch clamp data with the advantage of experiments being performed under close to physiological conditions. As a result, we demonstrate the up-regulation of gating of various Ca 2+ release channels due to Aβ pores and show that the extent and spatial range of such up-regulation increases as Aβ pores with low open probability and Ca 2+ permeability transition into those with high open probability and Ca 2+ permeability.« less

Environmental release of core–shell semiconductor nanocrystals from free-standing polymer nanocomposite films†

PubMed Central

Pillai, Karthik V.; Gray, Patrick J.; Tien, Chun-Chieh; Bleher, Reiner; Sung, Li-Piin

2016-01-01

Concomitant with the development of polymer nanocomposite (PNC) technologies across numerous industries is an expanding awareness of the uncertainty with which engineered nanoparticles embedded within these materials may be released into the external environment, particularly liquid media. Recently there has been an interest in evaluating potential exposure to nanoscale fillers from PNCs, but existing studies often rely upon uncharacterized, poor quality, or proprietary materials, creating a barrier to making general mechanistic conclusions about release phenomena. In this study we employed semiconductor nanoparticles (quantum dots, QDs) as model nanofillers to quantify potential release into liquid media under specific environmental conditions. QDs of two sizes were incorporated into low-density polyethylene by melt compounding and the mixtures were extruded as free-standing fluorescent films. These films were subjected to tests under conditions intended to accelerate potential release of embedded particles or dissolved residuals into liquid environments. Using inductively-coupled plasma mass spectrometry and laser scanning confocal microscopy, it was found that the acidity of the external medium, exposure time, and small differences in particle size (on the order of a few nm) all play pivotal roles in release kinetics. Particle dissolution was found to play a major if not dominant role in the release process. This paper also presents the first evidence that internally embedded nanoparticles contribute to the mass transfer, an observation made possible via the use of a model system that was deliberately designed to probe the complex relationships between nanoparticle-enabled plastics and the environment. PMID:27529026

Proton-pumping mechanism of cytochrome c oxidase: A kinetic master-equation approach

PubMed Central

Kim, Young C.; Hummer, Gerhard

2011-01-01

Cytochrome c oxidase (CcO) is an efficient energy transducer that reduces oxygen to water and converts the released chemical energy into an electrochemical membrane potential. As a true proton pump, CcO translocates protons across the membrane against this potential. Based on a wealth of experiments and calculations, an increasingly detailed picture of the reaction intermediates in the redox cycle has emerged. However, the fundamental mechanism of proton pumping coupled to redox chemistry remains largely unresolved. Here we examine and extend a kinetic master-equation approach to gain insight into redox-coupled proton pumping in CcO. Basic principles of the CcO proton pump emerge from an analysis of the simplest kinetic models that retain essential elements of the experimentally determined structure, energetics, and kinetics, and that satisfy fundamental physical principles. The master-equation models allow us to address the question of how pumping can be achieved in a system in which all reaction steps are reversible. Whereas proton pumping does not require the direct modulation of microscopic reaction barriers, such kinetic gating greatly increases the pumping efficiency. Further efficiency gains can be achieved by partially decoupling the proton uptake pathway from the ative-site region. Such a mechanism is consistent with the proposed Glu valve, in which the side chain of a key glutamic acid shuttles between the D channel and the active-site region. We also show that the models predict only small proton leaks even in the absence of turnover. The design principles identified here for CcO provide a blueprint for novel biology-inspired fuel cells, and the master-equation formulation should prove useful also for other molecular machines. PMID:21946020

Kinetic changes in tetanic Ca2+ transients in enzymatically dissociated muscle fibres under repetitive stimulation

PubMed Central

Calderón, Juan C; Bolaños, Pura; Caputo, Carlo

2011-01-01

Abstract We used enzymatically dissociated flexor digitorum brevis (FDB) and soleus fibres loaded with the fast Ca2+ dye Magfluo-4 AM, and adhered to Laminin, to test whether repetitive stimulation induces progressive changes in the kinetics of Ca2+ release and reuptake in a fibre-type-dependent fashion. We applied a protocol of tetani of 350 ms, 100 Hz, every 4 s to reach a mean amplitude reduction of 25% of the first peak. Morphology type I (MT-I) and morphology type II (MT-II) fibres underwent a total of 96 and 52.8 tetani (P < 0.01 between groups), respectively. The MT-II fibres (n = 18) showed significant reductions of the amplitude (19%), an increase in rise time (8.5%) and a further reduction of the amplitude/rise time ratio (25.5%) of the first peak of the tetanic transient after 40 tetani, while MT-I fibres (n = 5) did not show any of these changes. However, both fibre types showed significant reductions in the maximum rate of rise of the first peak after 40 tetani. Two subpopulations among the MT-II fibres could be distinguished according to Ca2+ reuptake changes. Fast-fatigable MT-II fibres (fMT-II) showed an increase of 32.2% in the half-width value of the first peak, while for fatigue-resistant MT-II fibres (rMT-II), the increase amounted to 6.9%, both after 40 tetani. Significant and non-significant increases of 36.4% and 11.9% in the first time constant of decay (t1) values were seen after 40 tetani in fMT-II and rMT-II fibres, respectively. MT-I fibres did not show kinetic changes in any of the Ca2+ reuptake variables. All changes were reversed after an average recovery of 7.5 and 15.4 min for MT-I and MT-II fibres, respectively. Further experiments ruled out the possibility that the differences in the kinetic changes of the first peak of the Ca2+ transients between fibres MT-I and MT-II could be related to the inactivation of Ca2+ release mechanism. In conclusion, we established a model of enzymatically dissociated fibres, loaded with Magfluo-4 and adhered to Laminin, to study muscle fatigue and demonstrated fibre-type-dependent, fatigue-induced kinetic changes in both Ca2+ release and reuptake. PMID:21878526

Benchtop-magnetic resonance imaging (BT-MRI) characterization of push-pull osmotic controlled release systems.

PubMed

Malaterre, Vincent; Metz, Hendrik; Ogorka, Joerg; Gurny, Robert; Loggia, Nicoletta; Mäder, Karsten

2009-01-05

The mechanism of drug release from push-pull osmotic systems (PPOS) has been investigated by Magnetic Resonance Imaging (MRI) using a new benchtop apparatus. The signal intensity profiles of both PPOS layers were monitored non-invasively over time to characterize the hydration and swelling kinetics. The drug release performance was well-correlated to the hydration kinetics. The results show that (i) hydration and swelling critically depend on the tablet core composition, (ii) high osmotic pressure developed by the push layer may lead to bypassing the drug layer and incomplete drug release and (iii) the hydration of both the drug and the push layers needs to be properly balanced to efficiently deliver the drug. MRI is therefore a powerful tool to get insights on the drug delivery mechanism of push-pull osmotic systems, which enable a more efficient optimization of such formulations.

Kinetics of killing Listeria monocytogenes by macrophages: correlation of /sup 3/H-DNA release from labeled bacteria and changes in numbers of viable organisms by mathematical model

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

Davies, W.A.

1982-12-01

Conventional methods of assessing antibacterial activities of macrophages by viable counting are limited by the precision of the statistics and are difficult to interpret quantitatively because of unrestrained extracellular growth of bacteria. An alternative technique based on the release of radioactive DNA from labeled bacteria has been offered as overcoming these drawbacks. To assess it for use with macrophages I have made a correlation with the conventional viable counting method using a mathematical model. Opsonized Listeria monocytogenes labeled with /sup 3/H-thymidine were exposed to rat macrophages for periods up to 4 hr. Numbers of viable bacteria determined after sonication increasedmore » exponentially in the absence of live cells and this growth rate was progressively inhibited by increasing numbers of macrophages. After a lag period of 30-60 min soluble /sup 3/H appeared in the supernatant, the amount increasing with time and numbers of macrophages. To correlate these data I developed a mathematical model that considered that changes in numbers of viable organisms were due to the difference between rates of 1) growth of extracellular bacteria and 2) killing within the macrophage. On the basis of this model curves of best fit to the viable counts data were used to predict the release of radioactivity, assuming that death of a bacterium led to the total release of its label. These predictions and the experimental data agreed well, the lag period of 30-60 min between death of the bacterium and release of radioactivity being consistent with intracellular digestion. Release of soluble radioactivity appears to be an accurate reflection of the number of bacteria killed within the macrophage.« less

Multiple-relaxation-time lattice Boltzmann kinetic model for combustion

NASA Astrophysics Data System (ADS)

Xu, Aiguo; Lin, Chuandong; Zhang, Guangcai; Li, Yingjun

2015-04-01

To probe both the hydrodynamic nonequilibrium (HNE) and thermodynamic nonequilibrium (TNE) in the combustion process, a two-dimensional multiple-relaxation-time (MRT) version of lattice Boltzmann kinetic model (LBKM) for combustion phenomena is presented. The chemical energy released in the progress of combustion is dynamically coupled into the system by adding a chemical term to the LB kinetic equation. Aside from describing the evolutions of the conserved quantities, the density, momentum, and energy, which are what the Navier-Stokes model describes, the MRT-LBKM presents also a coarse-grained description on the evolutions of some nonconserved quantities. The current model works for both subsonic and supersonic flows with or without chemical reaction. In this model, both the specific-heat ratio and the Prandtl number are flexible, the TNE effects are naturally presented in each simulation step. The model is verified and validated via well-known benchmark tests. As an initial application, various nonequilibrium behaviors, including the complex interplays between various HNEs, between various TNEs, and between the HNE and TNE, around the detonation wave in the unsteady and steady one-dimensional detonation processes are preliminarily probed. It is found that the system viscosity (or heat conductivity) decreases the local TNE, but increases the global TNE around the detonation wave, that even locally, the system viscosity (or heat conductivity) results in two kinds of competing trends, to increase and to decrease the TNE effects. The physical reason is that the viscosity (or heat conductivity) takes part in both the thermodynamic and hydrodynamic responses.

Synthesis and characterization of psyllium-NVP based drug delivery system through radiation crosslinking polymerization

NASA Astrophysics Data System (ADS)

Singh, Baljit; Kumar, S.

2008-08-01

In order to develop the hydrogels meant for the drug delivery, we have prepared psyllium- N-vinylpyrrolidone (NVP) based hydrogels by radiation induced crosslinking. Polymers were characterized with SEMs, FTIR and swelling studies. Swelling of the hydrogels was studied as a function of monomer concentration, total radiation dose, temperature, pH and [NaCl] of the swelling medium. The swelling kinetics of the hydrogels and release dynamics of anticancer model drug (5-fluorouracil) from the hydrogels have been carried out for the evaluation of swelling and drug release mechanism. It has been observed that diffusion exponent ' n' have 0.8, 0.9, 0.8 and gel characteristics constant ' k' have 9.22 × 10 -3, 2.06 × 10 -3, 11.72 × 10 -3 values for the release of drug from the drug loaded hydrogels in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively. The present study shows that the release of drug from the hydrogels occurred through Non-Fickian diffusion mechanism.

Synthesis and characterisation of multifunctional alginate microspheres via the in situ formation of ZnO quantum dots and the graft of 4-(1-pyrenyl) butyric acid to sodium alginate.

PubMed

Luo, Guilin; Wang, Jianxin; Wang, Yingying; Feng, Bo; Weng, Jie

2015-01-01

Growth factor-loaded fluorescent alginate microspheres, which can realise sustained growth factor release and fluorescence imaging, were synthesised by in situ formation of ZnO quantum dots (QDs) and covalent graft of 4-(1-pyrenyl) butyric acid (PBA). BSA was chosen as a growth factor model protein to study the release kinetic of growth factors from alginate microspheres. The microsphere size and fluorescent properties were also investigated. Investigations of cell culture were used for evaluating biocompatibility of BSA-loaded fluorescent microspheres and fluorescence imaging property of ZnO QDs and PBA-grafted sodium alginate from the microspheres. The results show that they have good fluorescent property either to microspheres or to cells and fluorescent microspheres have good biocompatibility and property in sustained release of growth factors. The obtained microspheres will be expected to realise the imaging of cells and materials and also the release of growth factor in tissue engineering or in cell culture.

Design, synthesis, characterization and drug release kinetics of PAMAM dendrimer based drug formulations

NASA Astrophysics Data System (ADS)

Kurtoglu, Yunus Emre

The drug release characteristics of G4-polyamidoamine (PAMAM) dendrimer-ibuprofen conjugates with ester, amide, and peptide linkers were investigated, in addition to a linear PEG-ibuprofen conjugate to understand the effect of architecture and linker on drug release. Ibuprofen was directly conjugated to NH2 -terminated dendrimer by an amide bond and OH-terminated dendrimer by an ester bond. A tetra-peptide linked dendrimer conjugate and a linear mPEG-ibuprofen conjugate were also studied for comparison to direct linked dendrimer conjugates. It is demonstrated that the 3-D nanoscale architecture of PAMAM dendrimer-drug conjugates, along with linking chemistry govern the drug release mechanisms as well as kinetics. Understanding these structural effects on their drug release characteristics is crucial for design of dendrimer conjugates with high efficacy such as poly(amidoamine) dendrimer-N-Acetylcysteine conjugates with disulfide linkages. N-Acetylcysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. A poly(amidoamine) dendrimer-NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), Cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. FITC-labeled conjugates showed that they enter cells rapidly and localize in the cytoplasm of lipopolysaccharide (LPS)-activated microglial cells. The efficacy of the dendrimer-NAC conjugate was measured in activated microglial cells using reactive oxygen species (ROS) assays. The conjugates showed an order of magnitude increase in anti-oxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.

Engineering bioceramic microstructure for customized drug delivery

NASA Astrophysics Data System (ADS)

Pacheco Gomez, Hernando Jose

One of the most efficient approaches to treat cancer and infection is to use biomaterials as a drug delivery system (DDS). The goal is for the material to provide a sustained release of therapeutic drug dose locally to target the ill tissue without affecting other organs. Silica Calcium Phosphate nano composite (SCPC) is a drug delivery platform that successfully demonstrated the ability to bind and release several therapeutics including antibiotics, anticancer drugs, and growth factors. The aim of the present work is to analyze the role of SCPC microstructure on drug binding and release kinetics. The main crystalline phases of SCPC are alpha-cristobalite (SiO2, Cris) and beta-rhenanite (NaCaPO4, Rhe); therefore, these two phases were prepared and characterized separately. Structural and compositional features of Cris, Rhe and SCPC bioceramics demonstrated a significant influence on the loading capacity and release kinetics profile of Vancomycin (Vanc) and Cisplatin (Cis). Fourier Transform Infrared (FTIR) spectroscopy analyses demonstrated that the P-O functional group in Rhe and SCPC has high affinity to the (C=O and N-H) of Vanc and (N-H and O-H) of Cis. By contrast, a weak chemical interaction between the Si-O functional group in Cris and SCPC and the two drugs was observed. Vanc loading per unit surface area increased in the order 8.00 microg Vanc/m2 for Rhe > 4.49 microg Vanc /m2 for SCPC>3.01 microg Vanc /m2 for Cris (p<0.05). Cis loading capacity increased in the order 8.59 microg Vanc /m2 for Cris, 17.8 microg Vanc/m2 for Rhe and 6.03 microg Vanc /m2 for SCPC (p<0.05). Drug release kinetics was dependent on the carrier as well as on the kind of drug. Different burst release and sustained release rates were measured for Vanc and Cis from the same carrier. The percentages of drug amount released from Cris, Rhe and SCPC during the burst stage (the first 2h) were: 50%, 50%, and 46% of Vanc; and 53.4%, 36.6%, and 30.6 % of Cis, respectively. Burst release was found to correlate with the pore size distribution and surface area. Furthermore, the average rates of sustained release in the period 8-216h from Cris, Rhe and SCPC were: 9.8, 7.2 and 3.5 mug/h of Vanc and 4.5, 5.3 and 3.5 mug/h of Cis, respectively. Nearly inert Cris ceramic showed release kinetics controlled by its hierarchical nano porous structure. On the other hand, the phase composition and surface chemistry of bioactive Rhe or SCPC ceramics overruled the effect of surface area. The relatively low rate of drug release from SCPC was due to the dissolution-back precipitation reaction taking place on the material surface as confirmed by FTIR bands of surface hydroxyapatite layer at 576.5, 596.7 and 620.7 cm-1. Moreover, the solid solution of crystalline phases of SCPC enhanced the bioactivity of the composite. Nuclear Magnetic Resonance (NMR) and cell culture analyses demonstrated that the interactions between the SCPC dissolution products and the released drug did not cause measurable negative effects on the bioactivity of the tested drugs. The therapeutic effects of the SCPC-Cis hybrid were evaluated using a rat model of hepatocellular carcinoma (HCC). Animals were treated by either systemic cisplatin injection (sCis), or with SCPC-Cis hybrid placed adjacent (ADJ) to, or within (IT), the tumor. Five days after implantation 50-55% of the total cisplatin loaded was released from the SCPC-Cis hybrids resulting in an approximately 50% decrease in tumor volume compared to sCis treatment. Severe side effects were observed in animals treated with sCis including rapid weight loss and decreased liver and kidney function, effects not observed in SCPC-Cis treated animals. Analysis of cisplatin distribution demonstrated drug concentrations in the tumor were 21 and 1.5-times higher in IT and ADJ groups, respectively, as compared to sCis treated animals. These data demonstrate the SCPC drug delivery system can provide an effective localized treatment for HCC with significantly reduced toxicity compared to systemic drug administration. Moreover, it is possible to tailor drug release kinetics from SCPC hybrids by controlling the crystalline structure of the material and the ratios of Cris and Rhe in the composite.

Comprehensive study of the drug delivery properties of poly(l-lactide)-poly(ethylene glycol) nanoparticles in rats and tumor-bearing mice.

PubMed

Shalgunov, Vladimir; Zaytseva-Zotova, Daria; Zintchenko, Arkadi; Levada, Tatiana; Shilov, Yuri; Andreyev, Dmitry; Dzhumashev, Dzhangar; Metelkin, Evgeny; Urusova, Alexandra; Demin, Oleg; McDonnell, Kevin; Troiano, Greg; Zale, Stephen; Safarovа, Elmira

2017-09-10

Nanoparticles made of polylactide-poly(ethylene glycol) block-copolymer (PLA-PEG) are promising vehicles for drug delivery due to their biodegradability and controllable payload release. However, published data on the drug delivery properties of PLA-PEG nanoparticles are heterogeneous in terms of nanoparticle characteristics and mostly refer to low injected doses (a few mg nanoparticles per kg body weight). We have performed a comprehensive study of the biodistribution of nanoparticle formulations based on PLA-PEG nanoparticles of ~100nm size at injected doses of 30 to 140mg/kg body weight in healthy rats and nude tumor-bearing mice. Nanoparticle formulations differed by surface PEG coverage and by release kinetics of the encapsulated model active pharmaceutical ingredient (API). Increase in PEG coverage prolonged nanoparticle circulation half-life up to ~20h in rats and ~10h in mice and decreased retention in liver, spleen and lungs. Circulation half-life of the encapsulated API grew monotonously as the release rate slowed down. Plasma and tissue pharmacokinetics was dose-linear for inactive nanoparticles, but markedly dose-dependent for the model therapeutic formulation, presumably because of the toxic effects of released API. A mathematical model of API distribution calibrated on the data for inactive nanoparticles and conventional API form correctly predicted the distribution of the model therapeutic formulation at the lowest investigated dose, but for higher doses the toxic action of the released API had to be explicitly modelled. Our results provide a coherent illustration of the ability of controllable-release PLA-PEG nanoparticles to serve as an effective drug delivery platform to alter API biodistribution. They also underscore the importance of physiological effects of released drug in determining the biodistribution of therapeutic drug formulations at doses approaching tolerability limits. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Pyrolysis of poly(vinyl chloride) and-electric arc furnacedust mixtures.

PubMed

Al-Harahsheh, Mohammad; Al-Otoom, Awni; Al-Makhadmah, Leema; Hamilton, Ian E; Kingman, Sam; Al-Asheh, Sameer; Hararah, Muhanned

2015-12-15

An investigation into the pyrolysis kinetics of PVC mixed with electric arc furnace dust (EAFD) was performed. Mixtures of both materials with varying PVC ratios (1:1, 1:2, 1:3) were prepared and pyrolyzed in a nitrogen atmosphere under dynamic heating conditions at different heating rates (5, 10, 30 and 50 °C/min). The pyrolysis process proceeded through two main decomposition steps; the first step involved the release of HCl which reacted with the metal oxides present in the dust, subsequently forming metal chlorides and water vapor. Benzene was also found to release as detected by TGA-MS. The remaining hydrocarbons in the polymer backbone decomposed further in the second step releasing further volatile hydrocarbons. Different models were used to fit the kinetic data namely the integral, the Van Krevelen, and Coats and Red fern methods. The presence of EAFD during PVC decomposition resulted in a considerable decrease in the activation energy of the reaction occurring during the first decomposition region. Furthermore, iron oxides were retained in the pyrolysis residue, whilst other valuable metals, including Zn and Pb, were converted to chlorides that are recoverable by leaching in water. It is believed that EAFD can be utilized as an active catalyst to produce energy gases such as propyneas evident from the TGA-MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Design, Development, and Optimization of Sterculia Gum-Based Tablet Coated with Chitosan/Eudragit RLPO Mixed Blend Polymers for Possible Colonic Drug Delivery

PubMed Central

Nath, Bipul; Nath, Lila Kanta

2013-01-01

The purpose of this study is to explore the possible applicability of Sterculia urens gum as a novel carrier for colonic delivery system of a sparingly soluble drug, azathioprine. The study involves designing a microflora triggered colon-targeted drug delivery system (MCDDS) which consists of a central polysaccharide core and is coated to different film thicknesses with blends of chitosan/Eudragit RLPO, and is overcoated with Eudragit L00 to provide acid and intestinal resistance. The microflora degradation property of gum was investigated in rat caecal medium. Drug release study in simulated colonic fluid revealed that swelling force of the gum could concurrently drive the drug out of the polysaccharide core due to the rupture of the chitosan/Eudargit coating in microflora-activated environment. Chitosan in the mixed film coat was found to be degraded by enzymatic action of the microflora in the colon. Release kinetic data revealed that the optimized MCDDS was fitted well into first-order model, and apparent lag time was found to be 6 hours, followed by Higuchi release kinetics. In vivo study in rabbits shows delayed T max, prolonged absorption time, decreased C max, and absorption rate constant (Ka), indicating a reduced systemic toxicity of the drug as compared to other dosage forms. PMID:26555985

Formulation, characterization, and in vitro/ex vivo evaluation of quercetin-loaded microemulsion for topical application.

PubMed

Kajbafvala, Azar; Salabat, Alireza; Salimi, Anayatollah

2016-12-09

The aim of this study was to develop a new microemulsion formulation for topical application of poorly soluble drug named quercetin. In order to design suitable microemulsion system, the pseudo-ternary phase diagrams of microemulsion systems were constructed at different surfactant/co-surfactant ratios using tween 80 as surfactant, transcutol ® P as a co-surfactant and oleic acid as an oil phase. Some physicochemical properties such as droplet size, density, refractive index, electrical conductivity, pH, surface tension, and viscosity of the microemulsion systems were measured at 298.15 K. The average hydrodynamic droplet size of the optimized microemulsions was obtained by dynamic light scattering method. Morphology assessment of the optimized quercetin-loaded microemulsion by transmission electron microscopy analysis indicated that the particles have the size of about 25 nm and spherical with narrow size distribution. Equilibrium solubility, in vitro drug release at a 24 h time period, release kinetic evaluation as well as ex vivo permeation and retention of quercetin-loaded microemulsions through rat skin has been investigated. The obtained results showed a slow release behavior without any transdermal delivery. Most of the formulations fitted best with zero-order kinetic model with a non-Fickian mechanisms. This study illustrated that the proposed QU-microemulsion has a good potential for use in sunscreen formulations. [Formula: see text].

Tuning model drug release and soft-tissue bioadhesion of polyester films by plasma post-treatment.

PubMed

Mogal, Vishal T; Yin, Chaw Su; O'Rorke, Richard; Boujday, Souhir; Méthivier, Christophe; Venkatraman, Subbu S; Steele, Terry W J

2014-04-23

Plasma treatments are investigated as a post-production method of tuning drug release and bioadhesion of poly(lactic-co-glycolic acid) (PLGA) thin films. PLGA films were treated under varying conditions by controlling gas flow rate, composition, treatment time, and radio frequency (RF) power. In vitro release of the drug-like molecule fluorescein diacetate (FDAc) from plasma-treated PLGA was tunable by controlling RF power; an increase of 65% cumulative release is reported compared to controls. Bioadhesion was sensitive to RF power and treatment time, assessed using ex vivo shear-stress tests with wetted swine aorta. We report a maximum bioadhesion ∼6-fold that of controls and 5-fold that of DOPA-based mussel adhesives tested to swine skin.1 The novelty of this post-treatment is the activation of a hydrophobic polyester film for bioadhesion, which can be quenched, while simultaneously tuning drug-release kinetics. This exemplifies the promise of plasma post-treatment for in-clinic bioadhesive activation, along with technological advancements, i.e., atmospheric plasma and hand-held "plasma pencils".

Impact of sodium caseinate concentration and location on magnesium release from multiple W/O/W emulsions.

PubMed

Bonnet, Marie; Cansell, Maud; Placin, Frédéric; Anton, Marc; Leal-Calderon, Fernando

2010-06-15

Water-in-oil-in-water (W/O/W) double emulsions were prepared and the rate of release of magnesium ions from the internal to the external aqueous phase was followed. Sodium caseinate was used not only as a hydrophilic surface-active species but also as a chelating agent able to bind magnesium ions. The release occurred without film rupturing (no coalescence). The kinetics of the release process depended on the location (in only one or in both aqueous compartments) and on the concentration of sodium caseinate. The rate of release increased with the concentration of sodium caseinate in the external phase and decreased when sodium caseinate was present in the inner droplets. The experiments were interpreted within the frame of a mean-field model based on diffusion, integrating the effect of ion binding. The data could be adequately fitted by considering a time-dependent permeation coefficient of the magnesium ions across the oil phase. Our results suggested that ion permeability was influenced by the state of the protein interfacial layers which itself depended on the extent of magnesium binding.

Formulation and evaluation of controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum

PubMed Central

Arora, Gurpreet; Malik, Karan; Singh, Inderbir; Arora, Sandeep; Rana, Vikas

2011-01-01

The aim of study was to prepare controlled release matrix mucoadhesive tablets of domperidone using Salvia plebeian gum as natural polymer. Tablets were formulated by direct compression technology employing the natural polymer in different concentrations (5, 10, 15 and 20% w/w). The prepared batches were evaluated for drug assay, diameter, thickness, hardness and tensile strength, swelling index, mucoadhesive strength (using texture analyzer) and subjected to in vitro drug release studies. Real-time stability studies were also conducted on prepared batches. In vitro drug release data were fitted in various release kinetic models for studying the mechanism of drug release. Tensile strength was found to increase from 0.808 ± 0.098 to 1.527 ± 0.10 mN/cm2 and mucoadhesive strength increased from 13.673 ± 1.542 to 40.378 ± 2.345 N, with an increase in the polymer concentration from 5 to 20% (A1 to A4). Swelling index was reported to increase with both increase in the concentration of gum and the time duration. The in vitro drug release decreased from 97.76 to 83.4% (A1 to A4) with the increase in polymer concentration. The drug release from the matrix tablets was found to follow zero-order and Higuchi models, indicating the matrix-forming potential of natural polymer. The value of n was found to be between 0.5221 and 0.8992, indicating the involvement of more than one drug release mechanism from the formulation and possibly the combination of both diffusion and erosion. These research findings clearly indicate the potential of S. plebeian gum to be used as binder, release retardant and mucoadhesive natural material in tablet formulations. PMID:22171313

A predictive computational model of the kinetic mechanism of stimulus-induced transducer methylation and feedback regulation through CheY in archaeal phototaxis and chemotaxis.

PubMed

Streif, Stefan; Oesterhelt, Dieter; Marwan, Wolfgang

2010-03-18

Photo- and chemotaxis of the archaeon Halobacterium salinarum is based on the control of flagellar motor switching through stimulus-specific methyl-accepting transducer proteins that relay the sensory input signal to a two-component system. Certain members of the transducer family function as receptor proteins by directly sensing specific chemical or physical stimuli. Others interact with specific receptor proteins like the phototaxis photoreceptors sensory rhodopsin I and II, or require specific binding proteins as for example some chemotaxis transducers. Receptor activation by light or a change in receptor occupancy by chemical stimuli results in reversible methylation of glutamate residues of the transducer proteins. Both, methylation and demethylation reactions are involved in sensory adaptation and are modulated by the response regulator CheY. By mathematical modeling we infer the kinetic mechanisms of stimulus-induced transducer methylation and adaptation. The model (deterministic and in the form of ordinary differential equations) correctly predicts experimentally observed transducer demethylation (as detected by released methanol) in response to attractant and repellent stimuli of wildtype cells, a cheY deletion mutant, and a mutant in which the stimulated transducer species is methylation-deficient. We provide a kinetic model for signal processing in photo- and chemotaxis in the archaeon H. salinarum suggesting an essential role of receptor cooperativity, antagonistic reversible methylation, and a CheY-dependent feedback on transducer demethylation.

Design of Block Copolymer Costabilized Nonionic Microemulsions and Their In Vitro and In Vivo Assessment as Carriers for Sustained Regional Delivery of Ibuprofen via Topical Administration.

PubMed

Djekic, Ljiljana; Martinovic, Martina; Stepanović-Petrović, Radica; Tomić, Maja; Micov, Ana; Primorac, Marija

2015-08-01

Nonionic surfactants (caprylocaproyl macrogol-8 glycerides, octoxynol-12, polysorbate-20, and polyethylene glycol-40 hydrogenated castor oil) (47.03%, w/w), costabilizer (poloxamer 407) (12%-20%, w/w), oil (isopropyl myristate) (5.22%, w/w), water (q.s. ad 100%, w/w), and ibuprofen (5%, w/w) were used to develop oil-in-water microemulsions with Newtonian flow behavior, low viscosity (from 368 ± 38 to 916 ± 46 mPa s), and average droplet size from 14.79 ± 0.31 to 16.54 ± 0.75 nm. Ibuprofen in vitro release from the microemulsions was in accordance with zero-order kinetics (R0(2) > 0.99) for at least 12 h. The maximum drug release rate (3.55%h(-1) ) was from the microemulsion M3 comprising 16%, w/w of poloxamer 407. The release rate of ibuprofen from the reference hydrogel followed Higuchi kinetics (RH(2) > 0.99), and drug amount released after the 6th hour was negligible. In a rat model of inflammation, the microemulsion M3 was significantly more efficacious than the reference hydrogel in exerting antihyperalgesic effects in prophylactic topical treatment, whereas they were comparable in therapeutic treatment as well as in producing antiedematous effect in both protocols. No obvious skin irritation was observed in in vivo studies. The developed nonionic surfactants-based microemulsions containing the optimal concentration of poloxamer 407 could be promising carriers for sustained regional delivery of ibuprofen via topical administration. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

Development and experimental design of a novel controlled-release matrix tablet formulation for indapamide hemihydrate.

PubMed

Antovska, Packa; Ugarkovic, Sonja; Petruševski, Gjorgji; Stefanova, Bosilka; Manchevska, Blagica; Petkovska, Rumenka; Makreski, Petre

2017-11-01

Development, experimental design and in vitro in vivo correlation (IVIVC) of controlled-release matrix formulation. Development of novel oral controlled delivery system for indapamide hemihydrate, optimization of the formulation by experimental design and evaluation regarding IVIVC on a pilot scale batch as a confirmation of a well-established formulation. In vitro dissolution profiles of controlled-release tablets of indapamide hemihydrate from four different matrices had been evaluated in comparison to the originator's product Natrilix (Servier) as a direction for further development and optimization of a hydroxyethylcellulose-based matrix controlled-release formulation. A central composite factorial design had been applied for the optimization of a chosen controlled-release tablet formulation. The controlled-release tablets with appropriate physical and technological properties had been obtained with a matrix: binder concentration variations in the range: 20-40w/w% for the matrix and 1-3w/w% for the binder. The experimental design had defined the design space for the formulation and was prerequisite for extraction of a particular formulation that would be a subject for transfer on pilot scale and IVIV correlation. The release model of the optimized formulation has shown best fit to the zero order kinetics depicted with the Hixson-Crowell erosion-dependent mechanism of release. Level A correlation was obtained.

A mathematical model for expected time to extinction of pathogenic bacteria through antibiotic

NASA Astrophysics Data System (ADS)

Ghosh, M. K.; Nandi, S.; Roy, P. K.

2016-04-01

Application of antibiotics in human system to prevent bacterial diseases like Gastritis, Ulcers, Meningitis, Pneumonia and Gonorrhea are indispensable. Antibiotics saved innumerable lives and continue to be a strong support for therapeutic application against pathogenic bacteria. In human system, bacterial diseases occur when pathogenic bacteria gets into the body and begin to reproduce and crowd out healthy bacteria. In this process, immature bacteria releases enzyme which is essential for bacterial cell-wall biosynthesis. After complete formation of cell wall, immature bacteria are converted to mature or virulent bacteria which are harmful to us during bacterial infections. Use of antibiotics as drug inhibits the bacterial cell wall formation. After application of antibiotics within body, the released bacterial enzyme binds with antibiotic molecule instead of its functional site during the cell wall synthesis in a competitive inhibition approach. As a consequence, the bacterial cell-wall formation as well as maturation process of pathogenic bacteria is halted and the disease is cured with lysis of bacterial cells. With this idea, a mathematical model has been developed in the present research investigation to review the inhibition of biosynthesis of bacterial cell wall by the application of antibiotics as drug in the light of enzyme kinetics. This approach helps to estimate the expected time to extinction of the pathogenic bacteria. Our mathematical approach based on the enzyme kinetic model for finding out expected time to extinction contributes favorable results for understanding of disease dynamics. Analytical and numerical results based on simulated findings validate our mathematical model.

Simulation of in situ uranium bioremediation with slow-release organic amendment injection

NASA Astrophysics Data System (ADS)

Zhang, F.; Parker, J.; Ye, M.; Tang, G.; Wu, W.; Mehlhorn, T.; Gihring, T. M.; Schadt, C.; Watson, D. B.; Brooks, S. C.

2010-12-01

In situ bioremediation of a highly uranium-contaminated gravel aquifer with a slow-release electron donor (emulsified edible oil) has been investigated at the US DOE Oak Ridge Integrated Field Research Challenge (ORIFRC) site in east Tennessee. Groundwater at the study location has pH ~6.7 and contains high concentrations of U (5-6 μM), sulfate (1.0-1.2) mM and Ca (3-4 mM). Diluted emulsified oil (20% solution) was injected into three injection wells within 1.5 hrs. Geochemical analysis of site groundwater demonstrated the sequential reduction of nitrate, Mn, Fe(III) and sulfate. The oil was degraded by indigenous microorganisms with acetate as a major product. Rapid removal of U(VI) from the aqueous phase occurred concurrently with acetate production and sulfate reduction. The field test data were analyzed using a reaction network with a kinetic model for lipid hydrolysis and glycerol fermentation and equilibrium reactions representing microbial reduction of sulfate, nitrate, iron, uranium, manganese and carbon dioxide based on the thermodynamic approach of Istok et al. (2010) using the parallelized HGC5 code. Model-simulated chemical concentrations and relative abundance of functional microbial populations are compared with field measurements. Application of the thermodynamically-based modeling approach instead of the widely used multi-Monod kinetic rate law to formulate bioreduction reactions substantially reduces the number of reaction parameters that need to be calibrated thus facilitating a more comprehensive representation of microbial community dynamics. The model developed through this study is expected to aid the design of future bioremediation strategies for the site.

Drug Release from ß-Cyclodextrin Complexes and Drug Transfer into Model Membranes Studied by Affinity Capillary Electrophoresis.

PubMed

Darwish, Kinda A; Mrestani, Yahya; Rüttinger, Hans-Hermann; Neubert, Reinhard H H

2016-05-01

Is to characterize the drug release from the ß-cyclodextrin (ß-CD) cavity and the drug transfer into model membranes by affinity capillary electrophoresis. Phospholipid liposomes with and without cholesterol were used to mimic the natural biological membrane. The interaction of cationic and anionic drugs with ß-CD and the interaction of the drugs with liposomes were detected separately by measuring the drug mobility in ß-CD containing buffer and liposome containing buffer; respectively. Moreover, the kinetics of drug release from ß-CD and its transfer into liposomes with or without cholesterol was studied by investigation of changes in the migration behaviours of the drugs in samples, contained drug, ß-CD and liposome, at 1:1:1 molar ratio at different time intervals; zero time, 30 min, 1, 2, 4, 6, 8, 10 and 24 h. Lipophilic drugs such as propranolol and ibuprofen were chosen for this study, because they form complexes with ß-CD. The mobility of the both drug liposome mixtures changed with time to a final state. For samples of liposomal membranes with cholesterol the final state was faster reached than without cholesterol. The study confirmed that the drug release from the CD cavity and its transfer into the model membrane was more enhanced by the competitive displacement of the drug from the ß-CD cavity by cholesterol, the membrane component. The ACE method here developed can be used to optimize the drug release from CD complexes and the drug transfer into model membranes.

Mathematical modeling of drug release from lipid dosage forms.

PubMed

Siepmann, J; Siepmann, F

2011-10-10

Lipid dosage forms provide an interesting potential for controlled drug delivery. In contrast to frequently used poly(ester) based devices for parenteral administration, they do not lead to acidification upon degradation and potential drug inactivation, especially in the case of protein drugs and other acid-labile active agents. The aim of this article is to give an overview on the current state of the art of mathematical modeling of drug release from this type of advanced drug delivery systems. Empirical and semi-empirical models are described as well as mechanistic theories, considering diffusional mass transport, potentially limited drug solubility and the leaching of other, water-soluble excipients into the surrounding bulk fluid. Various practical examples are given, including lipid microparticles, beads and implants, which can successfully be used to control the release of an incorporated drug during periods ranging from a few hours up to several years. The great benefit of mechanistic mathematical theories is the possibility to quantitatively predict the effects of different formulation parameters and device dimensions on the resulting drug release kinetics. Thus, in silico simulations can significantly speed up product optimization. This is particularly useful if long release periods (e.g., several months) are targeted, since experimental trial-and-error studies are highly time-consuming in these cases. In the future it would be highly desirable to combine mechanistic theories with the quantitative description of the drug fate in vivo, ideally including the pharmacodynamic efficacy of the treatments. Copyright © 2011 Elsevier B.V. All rights reserved.

Evaluating temperature and fuel stratification for heat-release rate control in a reactivity-controlled compression-ignition engine using optical diagnostics and chemical kinetics modeling

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

Musculus, Mark P. B.; Kokjohn, Sage L.; Reitz, Rolf D.

We investigated the combustion process in a dual-fuel, reactivity-controlled compression-ignition (RCCI) engine using a combination of optical diagnostics and chemical kinetics modeling to explain the role of equivalence ratio, temperature, and fuel reactivity stratification for heat-release rate control. An optically accessible engine is operated in the RCCI combustion mode using gasoline primary reference fuels (PRF). A well-mixed charge of iso-octane (PRF = 100) is created by injecting fuel into the engine cylinder during the intake stroke using a gasoline-type direct injector. Later in the cycle, n-heptane (PRF = 0) is delivered through a centrally mounted diesel-type common-rail injector. This injectionmore » strategy generates stratification in equivalence ratio, fuel blend, and temperature. The first part of this study uses a high-speed camera to image the injection events and record high-temperature combustion chemiluminescence. Moreover, the chemiluminescence imaging showed that, at the operating condition studied in the present work, mixtures in the squish region ignite first, and the reaction zone proceeds inward toward the center of the combustion chamber. The second part of this study investigates the charge preparation of the RCCI strategy using planar laser-induced fluorescence (PLIF) of a fuel tracer under non-reacting conditions to quantify fuel concentration distributions prior to ignition. The fuel-tracer PLIF data show that the combustion event proceeds down gradients in the n-heptane distribution. The third part of the study uses chemical kinetics modeling over a range of mixtures spanning the distributions observed from the fuel-tracer fluorescence imaging to isolate the roles of temperature, equivalence ratio, and PRF number stratification. The simulations predict that PRF number stratification is the dominant factor controlling the ignition location and growth rate of the reaction zone. Equivalence ratio has a smaller, but still significant, influence. Lastly, temperature stratification had a negligible influence due to the NTC behavior of the PRF mixtures.« less

Evaluating temperature and fuel stratification for heat-release rate control in a reactivity-controlled compression-ignition engine using optical diagnostics and chemical kinetics modeling

DOE PAGES

Musculus, Mark P. B.; Kokjohn, Sage L.; Reitz, Rolf D.

2015-04-23

We investigated the combustion process in a dual-fuel, reactivity-controlled compression-ignition (RCCI) engine using a combination of optical diagnostics and chemical kinetics modeling to explain the role of equivalence ratio, temperature, and fuel reactivity stratification for heat-release rate control. An optically accessible engine is operated in the RCCI combustion mode using gasoline primary reference fuels (PRF). A well-mixed charge of iso-octane (PRF = 100) is created by injecting fuel into the engine cylinder during the intake stroke using a gasoline-type direct injector. Later in the cycle, n-heptane (PRF = 0) is delivered through a centrally mounted diesel-type common-rail injector. This injectionmore » strategy generates stratification in equivalence ratio, fuel blend, and temperature. The first part of this study uses a high-speed camera to image the injection events and record high-temperature combustion chemiluminescence. Moreover, the chemiluminescence imaging showed that, at the operating condition studied in the present work, mixtures in the squish region ignite first, and the reaction zone proceeds inward toward the center of the combustion chamber. The second part of this study investigates the charge preparation of the RCCI strategy using planar laser-induced fluorescence (PLIF) of a fuel tracer under non-reacting conditions to quantify fuel concentration distributions prior to ignition. The fuel-tracer PLIF data show that the combustion event proceeds down gradients in the n-heptane distribution. The third part of the study uses chemical kinetics modeling over a range of mixtures spanning the distributions observed from the fuel-tracer fluorescence imaging to isolate the roles of temperature, equivalence ratio, and PRF number stratification. The simulations predict that PRF number stratification is the dominant factor controlling the ignition location and growth rate of the reaction zone. Equivalence ratio has a smaller, but still significant, influence. Lastly, temperature stratification had a negligible influence due to the NTC behavior of the PRF mixtures.« less

Using the Viking biology experimental results to obtain chemical information about Martian regolith

NASA Technical Reports Server (NTRS)

Plumb, Robert C.

1992-01-01

Although initially formulated as biology experiments, most of the results produced by the Viking Labeled Release (LR), Gas Exchange (GEX), and Pyrolytic Release (PR) experiments have been reproduced by chemical means. The experiments do not need more study as 'biological' phenomena, but they do deserve much more careful consideration from a chemical viewpoint. They are the only 'wet-chemical' experiments that scientists have performed on another planet, but they have not found very general use as sources of scientific information. There is a large set of potentially useful chemical observations, e.g., the three resolvable and precisely measured kinetic components of the release of C-14-labeled gases, the thermal sensitivity and magnitudes of the oxidation reaction(s) of the LR experiments, the kinetics and magnitude of the O2 and CO2 release of the GEX experiments, the thermal sensitivity of the GEX results, the differences between the thermal sensitivity of the GEX and the thermal sensitivity of the LR responses, and the kinetics and magnitudes of the LR successive injection reabsorption effect. It should be possible to test many chemical aspects of hypothetical martian phenomena in experiments using the biology experimental configurations and derive much valuable information by comparisons with the Viking observations.

Combined effect of attrition and ultrasound on the disruption of Pseudomonas putida for the efficient release of arginine deiminase.

PubMed

Patil, Mahesh D; Shinde, Ashok S; Dev, Manoj J; Patel, Gopal; Bhilare, Kiran D; Banerjee, Uttam Chand

2018-06-08

Disruption of Pseudomonas putida KT2440 by ultrasound treatment in a bath sonicator, in presence of the glass beads, was carried out for the release of arginine deiminase (ADI) and the results were compared with that of by Dyno-mill. The release of ADI depended mainly on the bead size and cellmass concentration being disrupted in bead mill. Nearly 23 U/mL ADI was released when slurry with a cell-mass concentration of 250 g/L was disintegrated for 9 min with 80% bead loading (0.25 mm) in Dyno-mill. Marginally higher amount of ADI (24.1 U/mL) was released by the bath sonication of 250 g/L cellmass slurry for 30 min with the beads (0.1 mm) and a sonication power of 170 W. The glass beads, suspended along with the cellmass slurry in bath sonicator, efficiently disrupted the microbial cells to release ADI. Variation in the kinetic constants for the performance parameters implied that ADI release and cell disruption kinetics is a function of disruption technique used and the process variables thereof. Estimation of location factor suggested that selective release of ADI can be achieved. This article is protected by copyright. All rights reserved. © 2018 American Institute of Chemical Engineers.

Kinetics of methane hydrate decomposition studied via in situ low temperature X-ray powder diffraction.

PubMed

Everett, S Michelle; Rawn, Claudia J; Keffer, David J; Mull, Derek L; Payzant, E Andrew; Phelps, Tommy J

2013-05-02

Gas hydrate is known to have a slowed decomposition rate at ambient pressure and temperatures below the melting point of ice. As hydrate exothermically decomposes, gas is released and water of the clathrate cages transforms into ice. Based on results from the decomposition of three nominally similar methane hydrate samples, the kinetics of two regions, 180-200 and 230-260 K, within the overall decomposition range 140-260 K, were studied by in situ low temperature X-ray powder diffraction. The kinetic rate constants, k(a), and the reaction mechanisms, n, for ice formation from methane hydrate were determined by the Avrami model within each region, and activation energies, E(a), were determined by the Arrhenius plot. E(a) determined from the data for 180-200 K was 42 kJ/mol and for 230-260 K was 22 kJ/mol. The higher E(a) in the colder temperature range was attributed to a difference in the microstructure of ice between the two regions.

Kinetics of Methane Hydrate Decomposition Studied via in Situ Low Temperature X-ray Powder Diffraction

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

Everett, Susan M; Rawn, Claudia J; Keffer, David J.

Gas hydrates are known to have a slowed decomposition rate at ambient pressure and temperatures below the melting point of ice termed self-preservation or anomalous preservation. As hydrate exothermically decomposes, gas is released and water of the clathrate cages transforms into ice. Two regions of slowed decomposition for methane hydrate, 180 200 K and 230 260 K, were observed, and the kinetics were studied by in situ low temperature x-ray powder diffraction. The kinetic constants for ice formation from methane hydrate were determined by the Avrami model within each region and activation energies, Ea, were determined by the Arrhenius plot.more » Ea determined from the data for 180 200 K was 42 kJ/mol and for 230 260 K was 22 kJ/mol. The higher Ea in the colder temperature range was attributed to a difference in the microstructure of ice between the two regions.« less

Characterization of poly(vinyl acetate) based floating matrix tablets.

PubMed

Strübing, Sandra; Metz, Hendrik; Mäder, Karsten

2008-03-03

Floating Kollidon SR matrix tablets containing Propranolol HCl were developed and characterized with respect to drug release characteristics and floating strength. Kollidon SR was able to delay Propranolol HCl release efficiently. Drug release kinetics was evaluated using the Korsmeyer-Peppas model and found to be governed by Fickian diffusion. Tablet floating started immediately and continued for 24 h. It was possible to monitor the floating strength of the matrix devices using a simple experimental setup. Floating strength was related to Kollidon SR level with improved floating characteristics for samples with a high polymer/drug ratio. Swelling characteristics of the tablets were analyzed by applying the equation according to Therien-Aubin et al. The influence of the polymer content on swelling characteristics was found to be only marginal. Furthermore, the new method of benchtop MRI was introduced to study the water diffusion and swelling behaviour non-invasively and continuously.

A Review of Disintegration Mechanisms and Measurement Techniques.

PubMed

Markl, Daniel; Zeitler, J Axel

2017-05-01

Pharmaceutical solid dosage forms (tablets or capsules) are the predominant form to administer active pharmaceutical ingredients (APIs) to the patient. Tablets are typically powder compacts consisting of several different excipients in addition to the API. Excipients are added to a formulation in order to achieve the desired fill weight of a dosage form, to improve the processability or to affect the drug release behaviour in the body. These complex porous systems undergo different mechanisms when they come in contact with physiological fluids. The performance of a drug is primarily influenced by the disintegration and dissolution behaviour of the powder compact. The disintegration process is specifically critical for immediate-release dosage forms. Its mechanisms and the factors impacting disintegration are discussed and methods used to study the disintegration in-situ are presented. This review further summarises mathematical models used to simulate disintegration phenomena and to predict drug release kinetics.

Thiol Modification of Psyllium Husk Mucilage and Evaluation of Its Mucoadhesive Applications

PubMed Central

Bhatia, Meenakshi

2013-01-01

Thiol functionalization of psyllium was carried out to enhance its mucoadhesive potential. Thiolation of psyllium was achieved by esterification with thioglycolic acid. Thiolation was observed to change the surface morphology of psyllium from fibrous to granular and result in a slight increase in the crystallinity and swelling. Thiolated psyllium was found to contain 3.282 m moles of thiol groups/g of the polymer. Mucoadhesive applications of thiolated psylium were explored by formulating gels using metronidazole as the model drug. On comparative evaluation thiolated psyllium gels showed 3-fold higher mucoadhesive strength than the psyllium gels as determined by modified physical balance using chicken buccal pouch. The results of in vitro release study revealed that thiolated psyllium gels provided a prolonged release of metronidazole. Further, the psyllium and thiolated psyllium gels were found to release the drug following first-order kinetics by combination of polymer relaxation and diffusion through the matrix. PMID:24348147