WorldWideScience

Sample records for amorphous solid dispersions

  1. The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion.

    Science.gov (United States)

    Milne, Marnus; Liebenberg, Wilna; Aucamp, Marique

    2015-10-01

    Zopiclone is a poorly soluble psychotherapeutic agent. The aim of this study was to prepare and characterize an amorphous form of zopiclone as well as the characterization and performance of a stable amorphous solid dispersion. The amorphous form was prepared by the well-known method of quench-cooling of the melt. The solid dispersion was prepared by a solvent evaporation method of zopiclone, polyvinylpyrrolidone-25 (PVP-25), and methanol, followed by freeze-drying. The physico-chemical properties and stability of amorphous zopiclone and the solid dispersion was studied using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), hot-stage microscopy (HSM), X-ray diffractometry (XRD), solubility, and dissolution studies. The zopiclone amorphous solid-state form was determined to be a fragile glass; it was concluded that the stability of the amorphous form is influenced by both temperature and water. Exposure of amorphous zopiclone to moisture results in rapid transformation of the amorphous form to the crystalline dihydrated form. In comparison, the amorphous solid dispersion proved to be more stable with increased aqueous solubility.

  2. Spray drying formulation of amorphous solid dispersions.

    Science.gov (United States)

    Singh, Abhishek; Van den Mooter, Guy

    2016-05-01

    Spray drying is a well-established manufacturing technique which can be used to formulate amorphous solid dispersions (ASDs) which is an effective strategy to deliver poorly water soluble drugs (PWSDs). However, the inherently complex nature of the spray drying process coupled with specific characteristics of ASDs makes it an interesting area to explore. Numerous diverse factors interact in an inter-dependent manner to determine the final product properties. This review discusses the basic background of ASDs, various formulation and process variables influencing the critical quality attributes (CQAs) of the ASDs and aspects of downstream processing. Also various aspects of spray drying such as instrumentation, thermodynamics, drying kinetics, particle formation process and scale-up challenges are included. Recent advances in the spray-based drying techniques are mentioned along with some future avenues where major research thrust is needed. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Physical stability of API/polymer-blend amorphous solid dispersions.

    Science.gov (United States)

    Lehmkemper, Kristin; Kyeremateng, Samuel O; Bartels, Mareike; Degenhardt, Matthias; Sadowski, Gabriele

    2018-03-01

    The preparation of amorphous solid dispersions (ASDs) is a well-established strategy for formulating active pharmaceutical ingredients by embedding them in excipients, usually amorphous polymers. Different polymers can be combined for designing ASDs with desired properties like an optimized dissolution behavior. One important criterion for the development of ASD compositions is the physical stability. In this work, the physical stability of API/polymer-blend ASDs was investigated by thermodynamic modeling and stability studies. Amorphous naproxen (NAP) and acetaminophen (APAP) were embedded in blends of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and either poly(vinylpyrrolidone) (PVP) or poly(vinylpyrrolidone-co-vinyl acetate) (PVPVA64). Parameters for modeling the API solubility in the blends and the glass-transition temperature curves of the water-free systems with Perturbed-Chain Statistical Associating Fluid Theory and Kwei equation, respectively, were correlated to experimental data. The phase behavior for standardized storage conditions (0%, 60% and 75% relative humidity (RH)) was predicted and compared to six months-long stability studies. According to modeling and experimental results, the physical stability was reduced with increasing HPMCAS content and increasing RH. This trend was observed for all investigated systems, with both APIs (NAP and APAP) and both polymer blends (PVP/HPMCAS and PVPVA64/HPMCAS). PC-SAFT and the Kwei equation turned out to be suitable tools for modeling and predicting the physical stability of the investigated API/polymer-blends ASDs. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. A Molecular-Level View of the Physical Stability of Amorphous Solid Dispersions

    Science.gov (United States)

    Yuan, Xiaoda

    Many pharmaceutical compounds being developed in recent years are poorly soluble in water. This has led to insufficient oral bioavailability of many compounds in vitro. The amorphous formulation is one of the promising techniques to increase the oral bioavailability of these poorly water-soluble compounds. However, an amorphous drug substance is inherently unstable because it is a high energy form. In order to increase the physical stability, the amorphous drug is often formulated with a suitable polymer to form an amorphous solid dispersion. Previous research has suggested that the formation of an intimately mixed drug-polymer mixture contributes to the stabilization of the amorphous drug compound. The goal of this research is to better understand the role of miscibility, molecular interactions and mobility on the physical stability of amorphous solid dispersions. Methods were developed to detect different degrees of miscibility on nanometer scale and to quantify the extent of hydrogen-bonding interactions between the drug and the polymer. Miscibility, hydrogen-bonding interactions and molecular mobility were correlated with physical stability during a six-month period using three model systems. Overall, this research provides molecular-level insights into many factors that govern the physical stability of amorphous solid dispersions which can lead to a more effective design of stable amorphous formulations.

  5. In vitro characterization of a novel polymeric system for preparation of amorphous solid drug dispersions.

    Science.gov (United States)

    Mahmoudi, Zahra N; Upadhye, Sampada B; Ferrizzi, David; Rajabi-Siahboomi, Ali R

    2014-07-01

    Preparation of amorphous solid dispersions using polymers is a commonly used formulation strategy for enhancing the solubility of poorly water-soluble drugs. However, often a single polymer may not bring about a significant enhancement in solubility or amorphous stability of a poorly water-soluble drug. This study describes application of a unique and novel binary polymeric blend in preparation of solid dispersions. The objective of this study was to investigate amorphous solid dispersions of glipizide, a BCS class II model drug, in a binary polymeric system of polyvinyl acetate phthalate (PVAP) and hypromellose (hydroxypropyl methylcellulose, HPMC). The solid dispersions were prepared using two different solvent methods: rotary evaporation (rotavap) and fluid bed drug layering on sugar spheres. The performance and physical stability of the dispersions were evaluated with non-sink dissolution testing, powder X-ray diffraction (PXRD), and modulated differential scanning calorimetry (mDSC). PXRD analysis demonstrated an amorphous state for glipizide, and mDSC showed no evidence of phase separation. Non-sink dissolution testing in pH 7.5 phosphate buffer indicated more than twofold increase in apparent solubility of the drug with PVAP-HPMC system. The glipizide solid dispersions demonstrated a high glass transition temperature (Tg) and acceptable chemical and physical stability during the stability period irrespective of the manufacturing process. In conclusion, the polymeric blend of PVAP-HPMC offers a unique formulation approach for developing amorphous solid dispersions with the flexibility towards the use of these polymers in different ratios and combined quantities depending on drug properties.

  6. Unipolar time-differential charge sensing in non-dispersive amorphous solids

    International Nuclear Information System (INIS)

    Goldan, A. H.; Rowlands, J. A.; Tousignant, O.; Karim, K. S.

    2013-01-01

    The use of high resistivity amorphous solids as photodetectors, especially amorphous selenium, is currently of great interest because they are readily produced over large area at substantially lower cost compared to grown crystalline solids. However, amorphous solids have been ruled out as viable radiation detection media for high frame-rate applications, such as single-photon-counting imaging, because of low carrier mobilities, transit-time-limited photoresponse, and consequently, poor time resolution. To circumvent the problem of poor charge transport in amorphous solids, we propose unipolar time-differential charge sensing by establishing a strong near-field effect using an electrostatic shield within the material. For the first time, we have fabricated a true Frisch grid inside a solid-state detector by evaporating amorphous selenium over photolithographically prepared multi-well substrates. The fabricated devices are characterized with optical, x-ray, and gamma-ray impulse-like excitations. Results prove the proposed unipolar time-differential property and show that time resolution in non-dispersive amorphous solids can be improved substantially to reach the theoretical limit set by spatial spreading of the collected Gaussian carrier cloud.

  7. Physicochemical characterization of atorvastatin calcium/ezetimibe amorphous nano-solid dispersions prepared by electrospraying method.

    Science.gov (United States)

    Jahangiri, Azin; Barzegar-Jalali, Mohammad; Javadzadeh, Yousef; Hamishehkar, Hamed; Adibkia, Khosro

    2017-09-01

    In the present study, electrospraying was applied as a novel method for the fabrication of amorphous nano-solid dispersions (N-SDs) of atorvastatin calcium (ATV), ezetimibe (EZT), and ATV/EZT combination as poorly water-soluble drugs. N-SDs were prepared using polyvinylpyrrolidone K30 as an amorphous carrier in 1:1 and 1:5 drug to polymer ratios and the total solid (including drug and polymer) concentrations of 10 and 20% (w/v). The prepared formulations were further investigated for their morphological, physicochemical, and dissolution properties. Scanning electron microscopy studies indicated that the morphology and diameter of the electrosprayed samples (ESs) were influenced by the solution concentration and drug:polymer ratio, so that an increase in the solution concentration resulted in fiber formation while an increase in the polymer ratio led to enhancement of the particle diameter. Differential scanning calorimetry and X-ray powder diffraction studies together with in vitro dissolution test revealed that the ESs were present in an amorphous form with improved dissolution properties. Infrared spectroscopic studies showed hydrogen-bonding interaction between the drug and polymer in ESs. Since the electrospraying method benefits from the both amorphization and nanosizing effect, this novel approach seems to be an efficient method for the fabrication of N-SDs of poorly water-soluble drugs.

  8. Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release.

    Science.gov (United States)

    Cao, Yizheng; Teng, Jing; Selbo, Jon

    2017-11-09

    Epigallocatechin gallate (EGCG) has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity) and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus ® 50:50 ( w / w ) shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

  9. Amorphous Solid Dispersion of Epigallocatechin Gallate for Enhanced Physical Stability and Controlled Release

    Directory of Open Access Journals (Sweden)

    Yizheng Cao

    2017-11-01

    Full Text Available Epigallocatechin gallate (EGCG has been recognized as the most prominent green tea extract due to its healthy influences. The high instability and low bioavailability, however, strongly limit its utilization in food and drug industries. This work, for the first time, develops amorphous solid dispersion of EGCG to enhance its bioavailability and physical stability. Four commonly used polymeric excipients are found to be compatible with EGCG in water-dioxane mixtures via a stepwise mixing method aided by vigorous mechanical interference. The dispersions are successfully generated by lyophilization. The physical stability of the dispersions is significantly improved compared to pure amorphous EGCG in stress condition (elevated temperature and relative humidity and simulated gastrointestinal tract environment. From the drug release tests, one of the dispersions, EGCG-Soluplus® 50:50 (w/w shows a dissolution profile that only 50% EGCG is released in the first 20 min, and the remains are slowly released in 24 h. This sustained release profile may open up new possibilities to increase EGCG bioavailability via extending its elimination time in plasma.

  10. Investigating the Dissolution Performance of Amorphous Solid Dispersions Using Magnetic Resonance Imaging and Proton NMR

    Directory of Open Access Journals (Sweden)

    Francesco Tres

    2015-09-01

    Full Text Available We have investigated the dissolution performance of amorphous solid dispersions of poorly water-soluble bicalutamide in a Kollidon VA64 polymeric matrix as a function of the drug loading (5% vs. 30% bicalutamide. A combined suite of state-of-the-art analytical techniques were employed to obtain a clear picture of the drug release, including an integrated magnetic resonance imaging UV-Vis flow cell system and 1H-NMR. Off-line 1H-NMR was used for the first time to simultaneously measure the dissolution profiles and rates of both the drug and the polymer from a solid dispersion. MRI and 1H-NMR data showed that the 5% drug loading compact erodes linearly, and that bicalutamide and Kollidon VA64 are released at approximately the same rate from the molecular dispersion. For the 30% extrudate, data indicated a slower water ingress into the compact which corresponds to a slower dissolution rate of both bicalutamide and Kollidon VA64.

  11. Amorphization of thiamine chloride hydrochloride: A study of the crystallization inhibitor properties of different polymers in thiamine chloride hydrochloride amorphous solid dispersions.

    Science.gov (United States)

    Arioglu-Tuncil, Seda; Bhardwaj, Vivekanand; Taylor, Lynne S; Mauer, Lisa J

    2017-09-01

    Amorphous solid dispersions of thiamine chloride hydrochloride (THCl) were created using a variety of polymers with different physicochemical properties in order to investigate how effective the various polymers were as THCl crystallization inhibitors. THCl:polymer dispersions were prepared by lyophilizing solutions of THCl and amorphous polymers (guar gum, pectin, κ-carrageenan, gelatin, and polyvinylpyrrolidone (PVP)). These dispersions were stored at select temperature (25 and 40°C) and relative humidity (0, 23, 32, 54, 75, and 85% RH) conditions and monitored at different time points using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). Moisture sorption isotherms of all samples were also obtained. Initially amorphous THCl was produced in the presence of ≥40% w/w pectin, κ-carrageenan, gelatin, and guar gum or ≥60% w/w PVP. Trends in polymer THCl crystallization inhibition (pectin≥κ-carrageenan>gelatin>guar gum≫PVP) were primarily based on the ability of the polymer to interact with THCl via hydrogen bonding and/or ionic interactions. The onset of THCl crystallization from the amorphous dispersions was also related to storage conditions. THCl remained amorphous at low RH conditions (0 and 23% RH) in all 1:1 dispersions except THCl:PVP. THCl crystallized in some dispersions below the glass transition temperature (T g ) but remained amorphous in others at T~T g . At high RHs (75 and 85% RH), THCl crystallized within one day in all samples. Given the ease of THCl amorphization in the presence of a variety of polymers, even at higher vitamin concentrations than would be found in foods, it is likely that THCl is amorphous in many low moisture foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A Miniaturized Extruder to Prototype Amorphous Solid Dispersions: Selection of Plasticizers for Hot Melt Extrusion.

    Science.gov (United States)

    Lauer, Matthias E; Maurer, Reto; Paepe, Anne T De; Stillhart, Cordula; Jacob, Laurence; James, Rajesh; Kojima, Yuki; Rietmann, Rene; Kissling, Tom; van den Ende, Joost A; Schwarz, Sabine; Grassmann, Olaf; Page, Susanne

    2018-05-19

    Hot-melt extrusion is an option to fabricate amorphous solid dispersions and to enhance oral bioavailability of poorly soluble compounds. The selection of suitable polymer carriers and processing aids determines the dissolution, homogeneity and stability performance of this solid dosage form. A miniaturized extrusion device (MinEx) was developed and Hypromellose acetate succinate type L (HPMCAS-L) based extrudates containing the model drugs neurokinin-1 (NK1) and cholesterylester transfer protein (CETP) were manufactured, plasticizers were added and their impact on dissolution and solid-state properties were assessed. Similar mixtures were manufactured with a lab-scale extruder, for face to face comparison. The properties of MinEx extrudates widely translated to those manufactured with a lab-scale extruder. Plasticizers, Polyethyleneglycol 4000 (PEG4000) and Poloxamer 188, were homogenously distributed but decreased the storage stability of the extrudates. Stearic acid was found condensed in ultrathin nanoplatelets which did not impact the storage stability of the system. Depending on their distribution and physicochemical properties, plasticizers can modulate storage stability and dissolution performance of extrudates. MinEx is a valuable prototyping-screening method and enables rational selection of plasticizers in a time and material sparing manner. In eight out of eight cases the properties of the extrudates translated to products manufactured in lab-scale extrusion trials.

  13. Pharmaceutical development of an amorphous solid dispersion formulation of elacridar hydrochloride for proof-of-concept clinical studies

    NARCIS (Netherlands)

    Sawicki, E.; Schellens, J. H M; Beijnen, J. H.; Nuijen, B.

    2017-01-01

    Objective: A novel tablet formulation containing an amorphous solid dispersion (ASD) of elacridar hydrochloride was developed with the purpose to resolve the drug’s low solubility in water and to conduct proof-of-concept clinical studies. Significance: Elacridar is highly demanded for

  14. Manufacturing Amorphous Solid Dispersions with a Tailored Amount of Crystallized API for Biopharmaceutical Testing.

    Science.gov (United States)

    Theil, Frank; Milsmann, Johanna; Anantharaman, Sankaran; van Lishaut, Holger

    2018-05-07

    The preparation of an amorphous solid dispersion (ASD) by dissolving a poorly water-soluble active pharmaceutical ingredient (API) in a polymer matrix can improve the bioavailability by orders of magnitude. Crystallization of the API in the ASD, though, is an inherent threat for bioavailability. Commonly, the impact of crystalline API on the drug release of the dosage form is studied with samples containing spiked crystallinity. These spiked samples possess implicit differences compared to native crystalline samples, regarding size and spatial distribution of the crystals as well as their molecular environment. In this study, we demonstrate that it is possible to grow defined amounts of crystalline API in solid dosage forms, which enables us to study the biopharmaceutical impact of actual crystallization. For this purpose, we studied the crystal growth in fenofibrate tablets over time under an elevated moisture using transmission Raman spectroscopy (TRS). As a nondestructive method to assess API crystallinity in ASD formulations, TRS enables the monitoring of crystal growth in individual dosage forms. Once the kinetic trace of the crystal growth for a certain environmental condition is determined, this method can be used to produce samples with defined amounts of crystallized API. To investigate the biopharmaceutical impact of crystallized API, non-QC dissolution methods were used, designed to identify differences between the various amounts of crystalline materials present. The drug release in the samples manufactured in this fashion was compared to that of samples with spiked crystallinity. In this study, we present for the first time a method for targeted crystallization of amorphous tablets to simulate crystallized ASDs. This methodology is a valuable tool to generate model systems for biopharmaceutical studies on the impact of crystallinity on the bioavailability.

  15. Preparation of amorphous solid dispersions by rotary evaporation and KinetiSol Dispersing: approaches to enhance solubility of a poorly water-soluble gum extract.

    Science.gov (United States)

    Bennett, Ryan C; Brough, Chris; Miller, Dave A; O'Donnell, Kevin P; Keen, Justin M; Hughey, Justin R; Williams, Robert O; McGinity, James W

    2015-03-01

    Acetyl-11-keto-β-boswellic acid (AKBA), a gum resin extract, possesses poor water-solubility that limits bioavailability and a high melting point making it difficult to successfully process into solid dispersions by fusion methods. The purpose of this study was to investigate solvent and thermal processing techniques for the preparation of amorphous solid dispersions (ASDs) exhibiting enhanced solubility, dissolution rates and bioavailability. Solid dispersions were successfully produced by rotary evaporation (RE) and KinetiSol® Dispersing (KSD). Solid state and chemical characterization revealed that ASD with good potency and purity were produced by both RE and KSD. Results of the RE studies demonstrated that AQOAT®-LF, AQOAT®-MF, Eudragit® L100-55 and Soluplus with the incorporation of dioctyl sulfosuccinate sodium provided substantial solubility enhancement. Non-sink dissolution analysis showed enhanced dissolution properties for KSD-processed solid dispersions in comparison to RE-processed solid dispersions. Variances in release performance were identified when different particle size fractions of KSD samples were analyzed. Selected RE samples varying in particle surface morphologies were placed under storage and exhibited crystalline growth following solid-state stability analysis at 12 months in comparison to stored KSD samples confirming amorphous instability for RE products. In vivo analysis of KSD-processed solid dispersions revealed significantly enhanced AKBA absorption in comparison to the neat, active substance.

  16. Polymer⁻Surfactant System Based Amorphous Solid Dispersion: Precipitation Inhibition and Bioavailability Enhancement of Itraconazole.

    Science.gov (United States)

    Feng, Disang; Peng, Tingting; Huang, Zhengwei; Singh, Vikramjeet; Shi, Yin; Wen, Ting; Lu, Ming; Quan, Guilan; Pan, Xin; Wu, Chuanbin

    2018-04-24

    The rapid release of poorly water-soluble drugs from amorphous solid dispersion (ASD) is often associated with the generation of supersaturated solution, which provides a strong driving force for precipitation and results in reduced absorption. Precipitation inhibitors, such as polymers and surfactants, are usually used to stabilize the supersaturated solution by blocking the way of kinetic or thermodynamic crystal growth. To evaluate the combined effect of polymers and surfactants on maintaining the supersaturated state of itraconazole (ITZ), various surfactants were integrated with enteric polymer hydroxypropyl methylcellulose acetate succinate (HPMC AS) to develop polymer⁻surfactant based solid dispersion. The supersaturation stability was investigated by in vitro supersaturation dissolution test and nucleation induction time measurement. Compared to the ASD prepared with HPMC AS alone, the addition of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) exhibited a synergistic effect on precipitation inhibition. The results indicated that the TPGS not only significantly reduced the degree of supersaturation which is the driving force for precipitation, but also provided steric hindrance to delay crystal growth by absorbing onto the surface of small particles. Subsequently, the formulations were evaluated in vivo in beagle dogs. Compared with commercial product Sporanox ® , the formulation prepared with HPMC AS/TPGS exhibited a 1.8-fold increase in the AUC (0⁻24 h) of ITZ and a 1.43-fold increase of hydroxyitraconazole (OH-ITZ) in the plasma. Similarly, the extent of absorption was increased by more than 40% when compared to the formulation prepared with HPMC AS alone. The results of this study demonstrated that the ASD based on polymer⁻surfactant system could obviously inhibit drug precipitation in vitro and in vivo, which provides a new access for the development of ASD for poorly water-soluble drug.

  17. Solid-State NMR Investigation of Drug-Excipient Interactions and Phase Behavior in Indomethacin-Eudragit E Amorphous Solid Dispersions.

    Science.gov (United States)

    Lubach, Joseph W; Hau, Jonathan

    2018-02-20

    To investigate the nature of drug-excipient interactions between indomethacin (IMC) and methacrylate copolymer Eudragit® E (EE) in the amorphous state, and evaluate the effects on formulation and stability of these amorphous systems. Amorphous solid dispersions containing IMC and EE were spray dried with drug loadings from 20% to 90%. PXRD was used to confirm the amorphous nature of the dispersions, and DSC was used to measure glass transition temperatures (T g ). 13 C and 15 N solid-state NMR was utilized to investigate changes in local structure and protonation state, while 1 H T 1 and T 1ρ relaxation measurements were used to probe miscibility and phase behavior of the dispersions. T g values for IMC-EE solid dispersions showed significant positive deviations from predicted values in the drug loading range of 40-90%, indicating a relatively strong drug-excipient interaction. 15 N solid-state NMR exhibited a change in protonation state of the EE basic amine, with two distinct populations for the EE amine at -360.7 ppm (unprotonated) and -344.4 ppm (protonated). Additionally, 1 H relaxation measurements showed phase separation at high drug load, indicating an amorphous ionic complex and free IMC-rich phase. PXRD data showed all ASDs up to 90% drug load remained physically stable after 2 years. 15 N solid-state NMR experiments show a change in protonation state of EE, indicating that an ionic complex indeed forms between IMC and EE in amorphous solid dispersions. Phase behavior was determined to exhibit nanoscale phase separation at high drug load between the amorphous ionic complex and excess free IMC.

  18. Initial Drug Dissolution from Amorphous Solid Dispersions Controlled by Polymer Dissolution and Drug-Polymer Interaction.

    Science.gov (United States)

    Chen, Yuejie; Wang, Shujing; Wang, Shan; Liu, Chengyu; Su, Ching; Hageman, Michael; Hussain, Munir; Haskell, Roy; Stefanski, Kevin; Qian, Feng

    2016-10-01

    To identify the key formulation factors controlling the initial drug and polymer dissolution rates from an amorphous solid dispersion (ASD). Ketoconazole (KTZ) ASDs using PVP, PVP-VA, HMPC, or HPMC-AS as polymeric matrix were prepared. For each drug-polymer system, two types of formulations with the same composition were prepared: 1. Spray dried dispersion (SDD) that is homogenous at molecular level, 2. Physical blend of SDD (80% drug loading) and pure polymer (SDD-PB) that is homogenous only at powder level. Flory-Huggins interaction parameters (χ) between KTZ and the four polymers were obtained by Flory-Huggins model fitting. Solution (13)C NMR and FT-IR were conducted to investigate the specific drug-polymer interaction in the solution and solid state, respectively. Intrinsic dissolution of both the drug and the polymer from ASDs were studied using a Higuchi style intrinsic dissolution apparatus. PXRD and confocal Raman microscopy were used to confirm the absence of drug crystallinity on the tablet surface before and after dissolution study. In solid state, KTZ is completely miscible with PVP, PVP-VA, or HPMC-AS, demonstrated by the negative χ values of -0.36, -0.46, -1.68, respectively; while is poorly miscible with HPMC shown by a positive χ value of 0.23. According to solution (13)C NMR and FT-IR studies, KTZ interacts with HPMC-AS strongly through H-bonding and dipole induced interaction; with PVPs and PVP-VA moderately through dipole-induced interactions; and with HPMC weakly without detectable attractive interaction. Furthermore, the "apparent" strength of drug-polymer interaction, measured by the extent of peak shift on NMR or FT-IR spectra, increases with the increasing number of interacting drug-polymer pairs. For ASDs with the presence of considerable drug-polymer interactions, such as KTZ/PVPs, KTZ/PVP-VA, or KTZ /HPMC-AS systems, drug released at the same rate as the polymer when intimate drug-polymer mixing was ensured (i.e., the SDD systems

  19. Investigation of itraconazole ternary amorphous solid dispersions based on povidone and Carbopol.

    Science.gov (United States)

    Meng, Fan; Meckel, Jordan; Zhang, Feng

    2017-08-30

    We investigate a ternary system that consists of itraconazole (ITZ) and two polymers: povidone K12 and Carbopol 907. The interactions between these two polymers and their effects on the properties of ternary ITZ amorphous solid dispersions (ASDs) are studied. These two polymers can form a water-insoluble complex in acidic aqueous media. The critical pH is determined to be 4.17. The weight percentage of Carbopol 907 in the interpolymer complex range from 59 to 70%, depending on the initial ratios between these two polymers in the starting solutions. This complexation is driven by a negative enthalpy change from the H-bonding between the two polymers and a positive entropy change from the freed water molecules. Due to the slow precipitation of the interpolymer complex in aqueous media, the attempt to prepare ternary ASD using solvent-controlled coprecipitation is not successful. Melt extrusion is identified to be the only viable method to prepare this ternary ASD. We find that interpolymer complex-based ASDs are physically less stable and demonstrate the poorest drug-release properties when compared to individual polymer-based binary ASDs. This study illustrates that the too strong interaction between polymers in ternary ASDs is detrimental to their performance. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Amorphous solid dispersions of piroxicam and Soluplus(®): Qualitative and quantitative analysis of piroxicam recrystallization during storage.

    Science.gov (United States)

    Lust, Andres; Strachan, Clare J; Veski, Peep; Aaltonen, Jaakko; Heinämäki, Jyrki; Yliruusi, Jouko; Kogermann, Karin

    2015-01-01

    The conversion of active pharmaceutical ingredient (API) from amorphous to crystalline form is the primary stability issue in formulating amorphous solid dispersions (SDs). The aim of the present study was to carry out qualitative and quantitative analysis of the physical solid-state stability of the SDs of poorly water-soluble piroxicam (PRX) and polyvinyl caprolactam-polyvinyl acetate-polyethylene-glycol graft copolymer (Soluplus(®)). The SDs were prepared by a solvent evaporation method and stored for six months at 0% RH/6 °C, 0% RH/25 °C, 40% RH/25 °C and 75% RH/25 °C. Fourier transform infrared spectroscopy equipped with attenuated total reflection accessory (ATR-FTIR) and Raman spectroscopy were used for characterizing the physical solid-state changes and drug-polymer interactions. The principal component analysis (PCA) and multivariate curve resolution alternating least squares (MCR-ALS) were used for the qualitative and quantitative analysis of Raman spectra collected during storage. When stored at 0% RH/6 °C and at 0% RH/25 °C, PRX in SDs remained in an amorphous form since no recrystallization was observed by ATR-FTIR and Raman spectroscopy. Raman spectroscopy coupled with PCA and MCR-ALS and ATR-FTIR spectroscopy enabled to detect the recrystallization of amorphous PRX in the samples stored at higher humidity. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. Effect of particle size of drug on conversion of crystals to an amorphous state in a solid dispersion with crospovidone.

    Science.gov (United States)

    Sugamura, Yuka; Fujii, Makiko; Nakanishi, Sayaka; Suzuki, Ayako; Shibata, Yusuke; Koizumi, Naoya; Watanabe, Yoshiteru

    2011-01-01

    The effect of particle size on amorphization of drugs in a solid dispersion (SD) was investigated for two drugs, indomethacin (IM) and nifedipine (NP). The SD of drugs were prepared in a mixture with crospovidone by a variety of mechanical methods, and their properties investigated by particle sizing, thermal analysis, and powder X-ray diffraction. IM, which had an initial particle size of 1 µm and tends to aggregate, was forced through a sieve to break up the particles. NP, which had a large initial particle size, was jet-milled. In both cases, reduction of the particle size of the drugs enabled transition to an amorphous state below the melting point of the drug. The reduction in particle size is considered to enable increased contact between the crospovidone and drug particles, increasing interactions between the two compounds. © 2011 Pharmaceutical Society of Japan

  2. Rheology Guided Rational Selection of Processing Temperature To Prepare Copovidone-Nifedipine Amorphous Solid Dispersions via Hot Melt Extrusion (HME).

    Science.gov (United States)

    Yang, Fengyuan; Su, Yongchao; Zhang, Jingtao; DiNunzio, James; Leone, Anthony; Huang, Chengbin; Brown, Chad D

    2016-10-03

    The production of amorphous solid dispersions via hot melt extrusion (HME) relies on elevated temperature and prolonged residence time, which can result in potential degradation and decomposition of thermally sensitive components. Herein, the rheological properties of a physical mixture of polymer and an active pharmaceutical ingredient (API) were utilized to guide the selection of appropriate HME processing temperature. In the currently studied copovidone-nifedipine system, a critical temperature, which is substantially lower (∼13 °C) than the melting point of crystalline API, was captured during a temperature ramp examination and regarded as the critical point at which the API could molecularly dissolve into the polymer. Based on the identification of this critical point, various solid dispersions were prepared by HME processing below, at, and above the critical temperature (both below and above the melting temperature (T m ) of crystalline API). In addition, the resultant extrudates along with two control solid dispersions prepared by physical mixing and cryogenic milling were assessed by X-ray diffraction, differential scanning calorimetry, hot stage microscopy, rheology, and solid-state NMR. Physicochemical properties of resultant solid dispersions indicated that the identified critical temperature is sufficient for the polymer-API system to reach a molecular-level mixing, manifested by the transparent and smooth appearance of extrudates, the absence of API crystalline diffraction and melting peaks, dramatically decreased rheological properties, and significantly improved polymer-API miscibility. Once the critical temperature has been achieved, further raising the processing temperature only results in limited improvement of API dispersion, reflected by slightly reduced storage modulus and complex viscosity and limited improvement in miscibility.

  3. Probing the mechanisms of drug release from amorphous solid dispersions in medium-soluble and medium-insoluble carriers.

    Science.gov (United States)

    Sun, Dajun D; Lee, Ping I

    2015-08-10

    The objective of the current study is to mechanistically differentiate the dissolution and supersaturation behaviors of amorphous drugs from amorphous solid dispersions (ASDs) based on medium-soluble versus medium-insoluble carriers under nonsink dissolution conditions through a direct head-to-head comparison. ASDs of indomethacin (IND) were prepared in several polymers which exhibit different solubility behaviors in acidic (pH1.2) and basic (pH7.4) dissolution media. The selected polymers range from water-soluble (e.g., PVP and Soluplus) and water-insoluble (e.g., ethylcellulose and Eudragit RL PO) to those only soluble in an acidic or basic dissolution medium (e.g., Eudragit E100, Eudragit L100, and HPMCAS). At 20wt.% drug loading, DSC and powder XRD analysis confirmed that the majority of incorporated IND was present in an amorphous state. Our nonsink dissolution results confirm that whether the carrier matrix is medium soluble determines the release mechanism of amorphous drugs from ASD systems which has a direct impact on the rate of supersaturation generation, thus in turn affecting the evolution of supersaturation in amorphous systems. For example, under nonsink dissolution conditions, the release of amorphous IND from medium-soluble carriers is governed by a dissolution-controlled mechanism leading to an initial surge of supersaturation followed by a sharp decline in drug concentration due to rapid nucleation and crystallization. In contrast, the dissolution of IND ASD from medium-insoluble carriers is more gradual as drug release is regulated by a diffusion-controlled mechanism by which drug supersaturation is built up gradually and sustained over an extended period of time without any apparent decline. Since several tested carrier polymers can be switched from soluble to insoluble by simply changing the pH of the dissolution medium, the results obtained here provide unequivocal evidence of the proposed transition of kinetic solubility profiles from the

  4. Numerical simulation of hot-melt extrusion processes for amorphous solid dispersions using model-based melt viscosity.

    Science.gov (United States)

    Bochmann, Esther S; Steffens, Kristina E; Gryczke, Andreas; Wagner, Karl G

    2018-03-01

    Simulation of HME processes is a valuable tool for increased process understanding and ease of scale-up. However, the experimental determination of all required input parameters is tedious, namely the melt rheology of the amorphous solid dispersion (ASD) in question. Hence, a procedure to simplify the application of hot-melt extrusion (HME) simulation for forming amorphous solid dispersions (ASD) is presented. The commercial 1D simulation software Ludovic ® was used to conduct (i) simulations using a full experimental data set of all input variables including melt rheology and (ii) simulations using model-based melt viscosity data based on the ASDs glass transition and the physical properties of polymeric matrix only. Both types of HME computation were further compared to experimental HME results. Variation in physical properties (e.g. heat capacity, density) and several process characteristics of HME (residence time distribution, energy consumption) among the simulations and experiments were evaluated. The model-based melt viscosity was calculated by using the glass transition temperature (T g ) of the investigated blend and the melt viscosity of the polymeric matrix by means of a T g -viscosity correlation. The results of measured melt viscosity and model-based melt viscosity were similar with only few exceptions, leading to similar HME simulation outcomes. At the end, the experimental effort prior to HME simulation could be minimized and the procedure enables a good starting point for rational development of ASDs by means of HME. As model excipients, Vinylpyrrolidone-vinyl acetate copolymer (COP) in combination with various APIs (carbamazepine, dipyridamole, indomethacin, and ibuprofen) or polyethylene glycol (PEG 1500) as plasticizer were used to form the ASDs. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Hot Melt Extruded Amorphous Solid Dispersion of Posaconazole with Improved Bioavailability: Investigating Drug-Polymer Miscibility with Advanced Characterisation

    Directory of Open Access Journals (Sweden)

    Ritesh Fule

    2014-01-01

    Full Text Available Invasive antifungal infections are reasons for morbidity and mortality in immunogenic patients worldwide. Posaconazole is a most promising antifungal agent against all types of invasive infections with high % of cure rate. The marketed suspension formulation has low bioavailability and is needed to be taken with food. In this paper, PCZ hot melt extruded amorphous solid dispersion (SD with immediate release and improved bioavailability was prepared using Soluplus (Sol as primary carrier for solubilization. Surfactants such as PEG 400, Lutrol F27, Lutrol F68, and TPGS are also used in combination with Soluplus to improve the physicochemical performance of the formulation when it comes in contact with GI (gastrointestinal fluid. Drug-polymer miscibility of SD was investigated using advanced techniques. In the in vivo study, the AUC(0–72 and Cmax of PCZ/Soluplus were 11.5 and 11.74 time higher than those of pure PCZ. The formulation of the extrudate SD had an AUC(0–72 and Cmax higher than those with the commercial capsule (Noxafil. Molecular dynamic (MD simulation studies were carried out using in silico molecular modelling to understand the drug-polymer intermolecular behaviour. The results of this research ensure enhanced dissolution and bioavailability of the solid dispersion of PCZ prepared by HME compared with the PCZ suspension.

  6. What Is the Mechanism Behind Increased Permeation Rate of a Poorly Soluble Drug from Aqueous Dispersions of an Amorphous Solid Dispersion?

    DEFF Research Database (Denmark)

    Frank, K. J.; Westedt, U.; Rosenblatt, K. M.

    2014-01-01

    of amorphous microparticles present in aqueous dispersions induces lasting supersaturation maintaining enhanced permeation. The hypothesis is supported by a slower drug permeation when the microparticles were removed. (c) 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci...

  7. Effects of tablet formulation and subsequent film coating on the supersaturated dissolution behavior of amorphous solid dispersions.

    Science.gov (United States)

    Sakai, Toshiro; Hirai, Daiki; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-04-05

    The effects of tablet preparation and subsequent film coating with amorphous solid dispersion (ASD) particles that were composed of a drug with poor water solubility and hydrophilic polymers were investigated. ASD particles were prepared with a drug and vinylpyrrolidone-vinyl acetate copolymer (PVPVA) or polyvinylpyrrolidone (PVP) at a weight ratio of 1:1 or 1:2 using a melt extrusion technique. Tablets were prepared by conventional direct compression followed by pan coating. A mathematical model based on the Noyes-Whitney equation assuming that stable crystals precipitated at the changeable surface area of the solid-liquid interface used to estimate drug dissolution kinetics in a non-sink dissolution condition. All the ASD particles showed a maximum dissolution concentration approximately ten times higher than that of the crystalline drug. The ASD particles with PVPVA showed higher precipitation rate with lower polymer ratio, while PVP did not precipitate within 960 min regardless of the polymer ratio, suggesting the ASD particles of 1:1 drug:PVPVA (ASD-1) were the most unstable among the ASD particles considered. The dissolution of a core tablet with ASD-1 showed less supersaturation and a much higher precipitation rate than those of ASD-1 particles. However, a film-coated tablet or core tablet with a trace amount of hydroxypropylmethylcellulose (HPMC) showed a similar dissolution profile to that of the ASD-1 particles, indicating HPMC had a remarkable precipitation inhibition effect. Overall, these results suggest that tablet preparation with ASD may adversely affect the maintenance of supersaturation; however, this effect can be mitigated by adding an appropriate precipitation inhibitor to the formulation. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Importance of in vitro dissolution conditions for the in vivo predictability of an amorphous solid dispersion containing a pH-sensitive carrier

    DEFF Research Database (Denmark)

    Wendelboe, Johan; Knopp, Matthias Manne; Khan, Fauzan

    2017-01-01

    as a carrier in amorphous solid dispersions of CCX. In vitro-in vivo correlation demonstrated that the in vitro data obtained in FaSSIF pH 7.4 was more predictive for the in vivo performance than that obtained in FaSSIF pH 6.5. Consequently, the findings of this study underline that when predicting the in vivo...

  9. Enhanced Supersaturation and Oral Absorption of Sirolimus Using an Amorphous Solid Dispersion Based on Eudragit® E

    Directory of Open Access Journals (Sweden)

    Youngseok Cho

    2015-05-01

    Full Text Available The present study aimed to investigate the effect of Eudragit® E/HCl (E-SD on the degradation of sirolimus in simulated gastric fluid (pH 1.2 and to develop a new oral formulation of sirolimus using E-SD solid dispersions to enhance oral bioavailability. Sirolimus-loaded solid dispersions were fabricated by a spray drying process. A kinetic solubility test demonstrated that the sirolimus/E-SD/TPGS (1/8/1 solid dispersion had a maximum solubility of 196.7 μg/mL within 0.5 h that gradually decreased to 173.4 μg/mL after 12 h. According to the dissolution study, the most suitable formulation was the sirolimus/E-SD/TPGS (1/8/1 solid dispersion in simulated gastric fluid (pH 1.2, owing to enhanced stability and degree of supersaturation of E-SD and TPGS. Furthermore, pharmacokinetic studies in rats indicated that compared to the physical mixture and sirolimus/HPMC/TPGS (1/8/1 solid dispersion, the sirolimus/E-SD/TPGS (1/8/1 solid dispersion significantly improved oral absorption of sirolimus. E-SD significantly inhibited the degradation of sirolimus in a dose-dependent manner. E-SD also significantly inhibited the precipitation of sirolimus compared to hydroxypropylmethyl cellulose (HPMC. Therefore, the results from the present study suggest that the sirolimus-loaded E-SD/TPGS solid dispersion has great potential in clinical applications.

  10. Pharmaceutical development of an oral tablet formulation containing a spray dried amorphous solid dispersion of docetaxel or paclitaxel

    NARCIS (Netherlands)

    Sawicki, Emilia; Beijnen, Jos H|info:eu-repo/dai/nl/071919570; Schellens, Jan H M|info:eu-repo/dai/nl/073926272; Nuijen, Bastiaan

    2016-01-01

    Previously, it was shown in Phase I clinical trials that solubility-limited oral absorption of docetaxel and paclitaxel can be drastically improved with a freeze dried solid dispersion (fdSD). These formulations, however, are unfavorable for further clinical research because of limitations in

  11. Downstream processing of a ternary amorphous solid dispersion: The impacts of spray drying and hot melt extrusion on powder flow, compression and dissolution.

    Science.gov (United States)

    Davis, Mark T; Potter, Catherine B; Walker, Gavin M

    2018-06-10

    Downstream processing aspects of a stable form of amorphous itraconazole exhibiting enhanced dissolution properties were studied. Preparation of this ternary amorphous solid dispersion by either spray drying or hot melt extrusion led to significantly different powder processing properties. Particle size and morphology was analysed using scanning electron microscopy. Flow, compression, blending and dissolution were studied using rheometry, compaction simulation and a dissolution kit. The spray dried material exhibited poorer flow and reduced sensitivity to aeration relative to the milled extrudate. Good agreement was observed between differing forms of flow measurement, such as Flow Function, Relative flow function, Flow rate index, Aeration rate, the Hausner ratio and the Carr index. The stability index indicated that both powders were stable with respect to agglomeration, de-agglomeration and attrition. Tablet ability and compressibility studies showed that spray dried material could be compressed into stronger compacts than extruded material. Blending of the powders with low moisture, freely-flowing excipients was shown to influence both flow and compression. Porosity studies revealed that blending could influence the mechanism of densification in extrudate and blended extrudate formulations. Following blending, the powders were compressed into four 500 mg tablets, each containing a 100 mg dose of amorphous itraconazole. Dissolution studies revealed that the spray dried material released drug faster and more completely and that blending excipients could further influence the dissolution rate. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. Understanding the generation and maintenance of supersaturation during the dissolution of amorphous solid dispersions using modulated DSC and 1H NMR.

    Science.gov (United States)

    Baghel, Shrawan; Cathcart, Helen; O'Reilly, Niall J

    2018-01-30

    In this study, the dissolution behaviour of dipyridamole (DPM) and cinnarizine (CNZ) spray-dried amorphous solid dispersions (ASDs) using polyvinyl pyrrolidone (PVP) and polyacrylic acid (PAA) as a carrier matrix were evaluated and compared. The drug concentrations achieved from the dissolution of PVP and PAA solid dispersions were significantly greater than the equilibrium solubility of crystalline DPM and CNZ in phosphate buffer pH 6.8 (PBS 6.8). The maximum drug concentration achieved by dissolution of PVP and PAA solid dispersions did not exceed the theoretically calculated apparent solubility of amorphous DPM and CNZ. However, the degree of supersaturation of DPM and CNZ increased considerably as the polymer weight fraction within the solid dispersion increased. In addition, the supersaturation profile of DPM and CNZ were studied in the presence and absence of the polymers. PAA was found to maintain a higher level of supersaturation compared to PVP. The enhanced drug solution concentration following dissolution of ASDs can be attributed to the reduced crystal growth rates of DPM and CNZ at an equivalent supersaturation. We have also shown that, for drugs having high crystallization tendency and weak drug-polymer interaction, the feasible way to increase dissolution might be increase the polymer weight fraction in the ASD. Solution 1 H NMR spectra were used to understand dissolution mechanism and to identify drug-polymer interaction. The change in electron densities of proton attached to different groups in DPM and CNZ suggested drug-polymer interaction in solution. The relative intensities of peak shift and nature of interaction between drug and polymer in different systems are different. These different effects suggest that DPM and CNZ interacts in a different way with PVP and PAA in solution which goes some way towards explaining the different polymeric effect, particularly in terms of inhibition of drug recrystallization and dissolution of DPM and CNZ ASDs

  13. The amorphous solid dispersion of the poorly soluble ABT-102 forms nano/microparticulate structures in aqueous medium: impact on solubility

    Directory of Open Access Journals (Sweden)

    Frank KJ

    2012-11-01

    Full Text Available Kerstin J Frank,1,3 Ulrich Westedt,2 Karin M Rosenblatt,2 Peter Hölig,2 Jörg Rosenberg,2 Markus Mägerlein,2 Gert Fricker,3 Martin Brandl11Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, Odense, Denmark; 2Abbott GmbH and Co. KG, Ludwigshafen, Germany; 3Department of Pharmaceutical Technology, University of Heidelberg, Heidelberg, GermanyAbstract: Amorphous solid dispersions (ASDs are a promising formulation approach for poorly soluble active pharmaceutical ingredients (APIs, because they ideally enhance both dissolution rate and solubility. However, the mechanism behind this is not understood in detail. In the present study, we investigated the supramolecular and the nano/microparticulate structures that emerge spontaneously upon dispersion of an ASD in aqueous medium and elucidated their influence on solubility. The ASD, prepared by hot melt extrusion, contained the poorly soluble ABT-102 (solubility in buffer, 0.05 µg/mL, a hydrophilic polymer, and three surfactants. The apparent solubility of ABT-102 from the ASD-formulation was enhanced up to 200 times in comparison to crystalline ABT-102. At the same time, the molecular solubility, as assessed by inverse equilibrium dialysis, was enhanced two times. Asymmetrical flow field-flow fractionation in combination with a multiangle light-scattering detector, an ultraviolet detector, and a refractometer enabled us to separate and identify the various supramolecular assemblies that were present in the aqueous dispersions of the API-free ASD (placebo and of binary/ternary blends of the ingredients. Thus, the supramolecular assemblies with a molar mass between 20,000 and 90,000 could be assigned to the polyvinylpyrrolidone/vinyl acetate 64, while two other kinds of assemblies were assigned to different surfactant assemblies (micelles. The amount of ABT-102 remaining associated with each of the assemblies upon fractionation was quantified offline with high

  14. Development of Tablet Formulation of Amorphous Solid Dispersions Prepared by Hot Melt Extrusion Using Quality by Design Approach.

    Science.gov (United States)

    Agrawal, Anjali; Dudhedia, Mayur; Deng, Weibin; Shepard, Kevin; Zhong, Li; Povilaitis, Edward; Zimny, Ewa

    2016-02-01

    The objective of the study was to identify the extragranular component requirements (level and type of excipients) to develop an immediate release tablet of solid dispersions prepared by hot melt extrusion (HME) process using commonly used HME polymers. Solid dispersions of compound X were prepared using polyvinyl pyrrolidone co-vinyl acetate 64 (PVP VA64), Soluplus, and hypromellose acetate succinate (HPMCAS-LF) polymers in 1:2 ratio by HME through 18 mm extruder. A mixture design was employed to study effect of type of polymer, filler (microcrystalline cellulose (MCC), lactose, and dicalcium phosphate anhydrous (DCPA)), and disintegrant (Crospovidone, croscarmellose sodium, and sodium starch glycolate (SSG)) as well as level of extrudates, filler, and disintegrant on tablet properties such as disintegration time (DT), tensile strength (TS), compactibility, and dissolution. Higher extrudate level resulted in longer DT and lower TS so 60-70% was the maximum amount of acceptable extrudate level in tablets. Fast disintegration was achieved with HPMCAS-containing tablets, whereas Soluplus- and PVP VA64-containing tablets had higher TS. Crospovidone and croscarmellose sodium were more suitable disintegrant than SSG to achieve short DT, and MCC was a suitable filler to prepare tablets with acceptable TS for each studied HME polymer. The influence of extragranular components on dissolution from tablets should be carefully evaluated while finalizing tablet composition, as it varies for each HME polymer. The developed statistical models identified suitable level of fillers and disintegrants for each studied HME polymer to achieve tablets with rapid DT (tablet porosity), and their predictivity was confirmed by conducting internal and external validation studies.

  15. Using Flory-Huggins phase diagrams as a pre-formulation tool for the production of amorphous solid dispersions: a comparison between hot-melt extrusion and spray drying.

    Science.gov (United States)

    Tian, Yiwei; Caron, Vincent; Jones, David S; Healy, Anne-Marie; Andrews, Gavin P

    2014-02-01

    Amorphous drug forms provide a useful method of enhancing the dissolution performance of poorly water-soluble drugs; however, they are inherently unstable. In this article, we have used Flory-Huggins theory to predict drug solubility and miscibility in polymer candidates, and used this information to compare spray drying and melt extrusion as processes to manufacture solid dispersions. Solid dispersions were prepared using two different techniques (hot-melt extrusion and spray drying), and characterised using a combination of thermal (thermogravimetric analysis and differential scanning calorimetry), spectroscopic (Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction methods. Spray drying permitted generation of amorphous solid dispersions across a wider drug concentration than melt extrusion. Melt extrusion provided sufficient energy for more intimate mixing to be achieved between drug and polymer, which may improve physical stability. It was also confirmed that stronger drug-polymer interactions might be generated through melt extrusion. Remixing and dissolution of recrystallised felodipine into the polymeric matrices did occur during the modulated differential scanning calorimetry analysis, but the complementary information provided from FTIR confirms that all freshly prepared spray-dried samples were amorphous with the existence of amorphous drug domains within high drug-loaded samples. Using temperature-composition phase diagrams to probe the relevance of temperature and drug composition in specific polymer candidates facilitates polymer screening for the purpose of formulating solid dispersions. © 2013 Royal Pharmaceutical Society.

  16. Fundamentals of amorphous solids structure and properties

    CERN Document Server

    Stachurski, Zbigniew H

    2014-01-01

    Long awaited, this textbook fills the gap for convincing concepts to describe amorphous solids. Adopting a unique approach, the author develops a framework that lays the foundations for a theory of amorphousness. He unravels the scientific mysteries surrounding the topic, replacing rather vague notions of amorphous materials as disordered crystalline solids with the well-founded concept of ideal amorphous solids. A classification of amorphous materials into inorganic glasses, organic glasses, glassy metallic alloys, and thin films sets the scene for the development of the model of ideal amorph

  17. Micro-scale prediction method for API-solubility in polymeric matrices and process model for forming amorphous solid dispersion by hot-melt extrusion.

    Science.gov (United States)

    Bochmann, Esther S; Neumann, Dirk; Gryczke, Andreas; Wagner, Karl G

    2016-10-01

    A new predictive micro-scale solubility and process model for amorphous solid dispersions (ASDs) by hot-melt extrusion (HME) is presented. It is based on DSC measurements consisting of an annealing step and a subsequent analysis of the glass transition temperature (Tg). The application of a complex mathematical model (BCKV-equation) to describe the dependency of Tg on the active pharmaceutical ingredient (API)/polymer ratio, enables the prediction of API solubility at ambient conditions (25°C). Furthermore, estimation of the minimal processing temperature for forming ASDs during HME trials could be defined and was additionally confirmed by X-ray powder diffraction data. The suitability of the DSC method was confirmed with melt rheological trials (small amplitude oscillatory system). As an example, ball milled physical mixtures of dipyridamole, indomethacin, itraconazole and nifedipine in poly(vinylpyrrolidone-co-vinylacetate) (copovidone) and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus®) were used. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) amorphous solid dispersions: Insights with confocal fluorescence microscopy.

    Science.gov (United States)

    Saboo, Sugandha; Taylor, Lynne S

    2017-08-30

    The aim of this study was to evaluate the utility of confocal fluorescence microscopy (CFM) to study the water-induced phase separation of miconazole-poly (vinylpyrrolidone-co-vinyl acetate) (mico-PVPVA) amorphous solid dispersions (ASDs), induced during preparation, upon storage at high relative humidity (RH) and during dissolution. Different fluorescent dyes were added to drug-polymer films and the location of the dyes was evaluated using CFM. Orthogonal techniques, in particular atomic force microscopy (AFM) coupled with nanoscale infrared spectroscopy (AFM-nanoIR), were used to provide additional analysis of the drug-polymer blends. The initial miscibility of mico-PVPVA ASDs prepared under low humidity conditions was confirmed by AFM-nanoIR. CFM enabled rapid identification of drug-rich and polymer-rich phases in phase separated films prepared under high humidity conditions. The identity of drug- and polymer-rich domains was confirmed using AFM-nanoIR imaging and localized IR spectroscopy, together with Lorentz contact resonance (LCR) measurements. The CFM technique was then utilized successfully to further investigate phase separation in mico-PVPVA films exposed to high RH storage and to visualize phase separation dynamics following film immersion in buffer. CFM is thus a promising new approach to study the phase behavior of ASDs, utilizing drug and polymer specific dyes to visualize the evolution of heterogeneity in films exposed to water. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability.

    Science.gov (United States)

    De Caro, Viviana; Ajovalasit, Alessia; Sutera, Flavia Maria; Murgia, Denise; Sabatino, Maria Antonietta; Dispenza, Clelia

    2017-06-24

    Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young's Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m². FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.

  20. Inelastic scattering from amorphous solids

    International Nuclear Information System (INIS)

    Price, D.L.

    1985-08-01

    The potential of inelastic neutron scattering techniques for surveying various aspects of the dynamics of amorphous solids is briefly reviewed. The recent use of the Intense Pulsed Neutron Source to provide detailed information on the optical vibrations of glasses is discussed in more detail. The density of states represents an averaged quantity which gives information about the general characteristics of the structure and bonding. More extensive information can be obtained by studying the detailed wavevector dependence of the dynamic structure factor. 15 refs., 7 figs

  1. Combined Effects of Supersaturation Rates and Doses on the Kinetic-Solubility Profiles of Amorphous Solid Dispersions Based on Water-Insoluble Poly(2-hydroxyethyl methacrylate) Hydrogels.

    Science.gov (United States)

    Schver, Giovanna C R M; Lee, Ping I

    2018-05-07

    Under nonsink dissolution conditions, the kinetic-solubility profiles of amorphous solid dispersions (ASDs) based on soluble carriers typically exhibit so-called "spring-and-parachute" concentration-time behaviors. However, the kinetic-solubility profiles of ASDs based on insoluble carriers (including hydrogels) are known to show sustained supersaturation during nonsink dissolution through a matrix-regulated diffusion mechanism by which the supersaturation of the drug is built up gradually and sustained over an extended period without any dissolved polymers acting as crystallization inhibitors. Despite previous findings demonstrating the interplay between supersaturation rates and total doses on the kinetic-solubility profiles of soluble amorphous systems (including ASDs based on dissolution-regulated releases from soluble polymer carriers), the combined effects of supersaturation rates and doses on the kinetic-solubility profiles of ASDs based on diffusion-regulated releases from water-insoluble carriers have not been investigated previously. Thus, the objective of this study is to examine the impacts of total doses and supersaturation-generation rates on the resulting kinetic-solubility profiles of ASDs based on insoluble hydrogel carriers. We employed a previously established ASD-carrier system based on water-insoluble-cross-linked-poly(2-hydroxyethyl methacrylate) (PHEMA)-hydrogel beads and two poorly water soluble model drugs: the weakly acidic indomethacin (IND) and the weakly basic posaconazole (PCZ). Our results show clearly for the first time that by using the smallest-particle-size fraction and a high dose (i.e., above the critical dose), it is indeed possible to significantly shorten the duration of sustained supersaturation in the kinetic-solubility profile of an ASD based on a water-insoluble hydrogel carrier, such that it resembles the spring-and-parachute dissolution profiles normally associated with ASDs based on soluble carriers. This generates

  2. A comparative study of the effect of spray drying and hot-melt extrusion on the properties of amorphous solid dispersions containing felodipine.

    Science.gov (United States)

    Mahmah, Osama; Tabbakh, Rami; Kelly, Adrian; Paradkar, Anant

    2014-02-01

    To compare the properties of solid dispersions of felodipine for oral bioavailability enhancement using two different polymers, polyvinylpyrrolidone (PVP) and hydroxypropyl methylcellulose acetate succinate (HPMCAS), by hot-melt extrusion (HME) and spray drying. Felodipine solid dispersions were prepared by HME and spray drying techniques. PVP and HPMCAS were used as polymer matrices at different drug : polymer ratios (1 : 1, 1 : 2 and 1 : 3). Detailed characterization was performed using differential scanning calorimetry, powder X-ray diffractometry, scanning electron microscopy and in-vitro dissolution testing. Dissolution profiles were evaluated in the presence of sodium dodecyl sulphate. Stability of different solid dispersions was studied under accelerated conditions (40°C/75% RH) over 8 weeks. Spray-dried formulations were found to release felodipine faster than melt extruded formulations for both polymer matrices. Solid dispersions containing HMPCAS exhibited higher drug release rates and better wettability than those produced with a PVP matrix. No significant differences in stability were observed except with HPMCAS at a 1 : 1 ratio, where crystallization was detected in spray-dried formulations. Solid dispersions of felodipine produced by spray drying exhibited more rapid drug release than corresponding melt extruded formulations, although in some cases improved stability was observed for melt extruded formulations. © 2013 Royal Pharmaceutical Society.

  3. Accelerated Physical Stability Testing of Amorphous Dispersions.

    Science.gov (United States)

    Mehta, Mehak; Suryanarayanan, Raj

    2016-08-01

    The goal was to develop an accelerated physical stability testing method of amorphous dispersions. Water sorption is known to cause plasticization and may accelerate drug crystallization. In an earlier investigation, it was observed that both the increase in mobility and decrease in stability in amorphous dispersions was explained by the "plasticization" effect of water (Mehta et al. Mol. Pharmaceutics 2016, 13 (4), 1339-1346). In this work, the influence of water concentration (up to 1.8% w/w) on the correlation between mobility and crystallization in felodipine dispersions was investigated. With an increase in water content, the α-relaxation time as well as the time for 1% w/w felodipine crystallization decreased. The relaxation times of the systems, obtained with different water concentration, overlapped when the temperature was scaled (Tg/T). The temperature dependencies of the α-relaxation time as well as the crystallization time were unaffected by the water concentration. Thus, the value of the coupling coefficient, up to a water concentration of 1.8% w/w, was approximately constant. Based on these findings, the use of "water sorption" is proposed to build predictive models for crystallization in slow crystallizing dispersions.

  4. Cefuroxime axetil solid dispersions prepared using solution enhanced dispersion by supercritical fluids.

    Science.gov (United States)

    Jun, Seoung Wook; Kim, Min-Soo; Jo, Guk Hyun; Lee, Sibeum; Woo, Jong Soo; Park, Jeong-Sook; Hwang, Sung-Joo

    2005-12-01

    Cefuroxime axetil (CA) solid dispersions with HPMC 2910/PVP K-30 were prepared using solution enhanced dispersion by supercritical fluids (SEDS) in an effort to increase the dissolution rate of poorly water-soluble drugs. Their physicochemical properties in solid state were characterized by differential scanning calorimeter (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectrometry (FT-IR) and scanning electron microscopy. No endothermic and characteristic diffraction peaks corresponding to CA were observed for the solid dispersions in DSC and PXRD. FTIR analysis demonstrated the presence of intermolecular hydrogen bonds between CA and HPMC 2910/PVP K-30 in solid dispersions, resulting in the formation of amorphous or non-crystalline CA. Dissolution studies indicated that the dissolution rates were remarkably increased in solid dispersions compared with those in the physical mixture and drug alone. In conclusion, an amorphous or non-crystalline CA solid dispersion prepared using SEDS could be very useful for the formulation of solid dosage forms.

  5. Hydrogen in disordered and amorphous solids

    International Nuclear Information System (INIS)

    Bambakidis, G; Bowman, R.C.

    1986-01-01

    This book presents information on the following topoics: elements of the theory of amorphous semiconductors; electronic structure of alpha-SiH; fluctuation induced gap states in amorphous hydrogenated silicon; hydrogen on semiconductor surfaces; the influence of hydrogen on the defects and instabilities in hydrogenated amorphous silicon; deuteron magnetic resonance in some amorphous semiconductors; formation of amorphous metals by solid state reactions of hydrogen with an intermetallic compound; NMR studies of the hydrides of disordered and amorphous alloys; neutron vibrational spectroscopy of disordered metal-hydrogen system; dynamical disorder of hydrogen in LaNi /SUB 5-y/ M /SUB y/ hydrides studied by quasi-elastic neutron scattering; recent studies of intermetallic hydrides; tritium in Pd and Pd /SUB 0.80/ Sg /SUB 0.20/ ; and determination of hydrogen concentration in thin films of absorbing materials

  6. Prediction of Phase Behavior of Spray-Dried Amorphous Solid Dispersions: Assessment of Thermodynamic Models, Standard Screening Methods and a Novel Atomization Screening Device with Regard to Prediction Accuracy

    Directory of Open Access Journals (Sweden)

    Aymeric Ousset

    2018-03-01

    Full Text Available The evaluation of drug–polymer miscibility in the early phase of drug development is essential to ensure successful amorphous solid dispersion (ASD manufacturing. This work investigates the comparison of thermodynamic models, conventional experimental screening methods (solvent casting, quench cooling, and a novel atomization screening device based on their ability to predict drug–polymer miscibility, solid state properties (Tg value and width, and adequate polymer selection during the development of spray-dried amorphous solid dispersions (SDASDs. Binary ASDs of four drugs and seven polymers were produced at 20:80, 40:60, 60:40, and 80:20 (w/w. Samples were systematically analyzed using modulated differential scanning calorimetry (mDSC and X-ray powder diffraction (XRPD. Principal component analysis (PCA was used to qualitatively assess the predictability of screening methods with regards to SDASD development. Poor correlation was found between theoretical models and experimentally-obtained results. Additionally, the limited ability of usual screening methods to predict the miscibility of SDASDs did not guarantee the appropriate selection of lead excipient for the manufacturing of robust SDASDs. Contrary to standard approaches, our novel screening device allowed the selection of optimal polymer and drug loading and established insight into the final properties and performance of SDASDs at an early stage, therefore enabling the optimization of the scaled-up late-stage development.

  7. Analysis of an ideal amorphous solid

    International Nuclear Information System (INIS)

    To, L.T.; Stachurski, Z.H.

    2004-01-01

    Full text: In geometrical terms, amorphous solids are fundamentally different from crystalline solids in that they can not be constructed by the crystallographic method of translation of the basis along a lattice. Therefore, to study amorphous structures we must invoke concepts and use measures different to those used for ordered structures. Nevertheless, an ideal amorphous solid must share together with the ideal crystalline solid in the same definition of the term 'ideal'. In both cases it must be a perfect body, in which perfection is carried through in every detail to an unlimited (infinite) size without fault or defect. The latest results on this research will be presented. To qualify for a solid, rigid body, close packing of the spheres is required. For an ideal amorphous solids composed of hard spheres of identical size, we impose a stricter condition for the packing, namely, to be such that all spheres are in fixed positions (no loose spheres). To define the ideal solid, we must define what we mean by a perfect amorphous structure. Here, perfection is defined by, first the definition of imperfections, and next by the requirement of absence of imperfections of any kind. We envisage two types of defects: (i) geometrical, and (ii) statistical. Geometrical defects are: a sphere of different size, a loose sphere, and a vacancy. A statistical defect is defined with respect to two statistical functions: Ψ(N C ), and Φ(S β ). The former describes the probability of a given sphere having nc number of touching contacts, and the latter describes the disposition of the contacts on the surface of the sphere. Defects relating to the two functions will be described. The results for the functions, Ψ(N C ), and Φ(S β ), for the corresponding radial distribution function, and so called blocking number will be presented from simulations of an ideal amorphous solid

  8. Magnetomechanical coupling in thermal amorphous solids

    Science.gov (United States)

    Hentschel, H. George E.; Ilyin, Valery; Mondal, Chandana; Procaccia, Itamar

    2018-05-01

    Standard approaches to magnetomechanical interactions in thermal magnetic crystalline solids involve Landau functionals in which the lattice anisotropy and the resulting magnetization easy axes are taken explicitly into account. In glassy systems one needs to develop a theory in which the amorphous structure precludes the existence of an easy axis, and in which the constituent particles are free to respond to their local amorphous surroundings and the resulting forces. We present a theory of all the mixed responses of an amorphous solid to mechanical strains and magnetic fields. Atomistic models are proposed in which we test the predictions of magnetostriction for both bulk and nanofilm amorphous samples in the paramagnetic phase. The application to nanofilms with emergent self-affine free interfaces requires a careful definition of the film "width" and its change due to the magnetostriction effect.

  9. Interaction Study of an Amorphous Solid Dispersion of Cyclosporin A in Poly-Alpha-Cyclodextrin with Model Membranes by 1H-, 2H-, 31P-NMR and Electron Spin Resonance

    Directory of Open Access Journals (Sweden)

    Jean-Claude Debouzy

    2014-01-01

    Full Text Available The properties of an amorphous solid dispersion of cyclosporine A (ASD prepared with the copolymer alpha cyclodextrin (POLYA and cyclosporine A (CYSP were investigated by 1H-NMR in solution and its membrane interactions were studied by 1H-NMR in small unilamellar vesicles and by 31P 2H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine in comparison with those of POLYA and CYSP alone. 1H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1 : 1 stoichiometry. Calculations gave an apparent association constant of log Ka = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level (31P. Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD.

  10. Sodium Lauryl Sulfate Competitively Interacts with HPMC-AS and Consequently Reduces Oral Bioavailability of Posaconazole/HPMC-AS Amorphous Solid Dispersion.

    Science.gov (United States)

    Chen, Yuejie; Wang, Shujing; Wang, Shan; Liu, Chengyu; Su, Ching; Hageman, Michael; Hussain, Munir; Haskell, Roy; Stefanski, Kevin; Qian, Feng

    2016-08-01

    Sodium lauryl sulfate (SLS), as an effective surfactant, is often used as a solubilizer and/or wetting agent in various dosage forms for the purpose of improving the solubility and dissolution of lipophilic, poorly water-soluble drugs. This study aims to understand the impact of SLS on the solution behavior and bioavailability of hypromellose acetate succinate (HPMC-AS)-based posaconazole (PSZ) ASDs, and to identify the underlying mechanisms governing the optimal oral bioavailability of ASDs when surfactants such as SLS are used in combination. Fluorescence spectroscopy and optical microscopy showed that "oil-out" or "liquid-liquid phase separation (LLPS)" occurred in the supersaturated PSZ solution once drug concentration surpassed ∼12 μg/mL, which caused the formation of drug-rich oily droplets with initial size of ∼300-400 nm. Although FT-IR study demonstrated the existence of specific interactions between PSZ and HPMC-AS in the solid state, predissolved HPMC-AS was unable to delay LLPS of the supersaturated PSZ solution and PSZ-rich amorphous precipitates with ∼16-18% HPMC-AS were formed within 10 min. The coprecipitated HPMC-AS was found to be able to significantly delay the crystallization of PSZ in the PSZ-rich amorphous phase from less than 10 min to more than 4 h, yet coexistent SLS was able to negate this crystallization inhibition effect of HPMC-AS in the PSZ-rich amorphous precipitates and cause fast PSZ crystallization within 30 min. 2D-NOESY and the CMC/CAC results demonstrated that SLS could assemble around HPMC-AS and competitively interact with HPMC-AS in the solution, thus prevent HPMC-AS from acting as an effective crystallization inhibitor. In a crossover dog PK study, this finding was found to be correlating well with the in vivo bioavailability of PSZ ASDs formulated with or without SLS. The SLS containing PSZ ASD formulation demonstrated an in vivo bioavailability ∼30% of that without SLS, despite the apparently better in vitro

  11. Amorphous ice. A microporous solid: astrophysical implications

    International Nuclear Information System (INIS)

    Mayer, E.; Pletzer, R.

    1987-01-01

    Vapour deposited amorphous ice, investigated by N 2 -adsorption at 77 K, was found to be a microporous solid. Micropore volumes between 0.21 and 0.12 cm 3 /g were determined by comparison plots and Dubinin-Radushkevich plots. Warming of the adsorbent to 113 K caused sintering and reduction of apparent surface area by about an order of magnitude; in the presence of adsorbed gas, large amounts of gas were enclosed in the solid. The influence of micropores on the H 2 recombination rate on amorphous ice in interstellar dust and on adsorption of volatile gases in comets is discussed briefly

  12. Phonon excitations in multicomponent amorphous solids

    International Nuclear Information System (INIS)

    Vakarchuk, I.A.; Migal', V.M.; Tkachuk, V.M.

    1988-01-01

    The method of two-time temperature-dependent Green's functions is used to investigate phonon excitations in multicomponent amorphous solids. The equation obtained for the energy spectrum of the phonon excitations takes into account the damping associated with scattering of phonons by structure fluctuations. The quasicrystal approximation is considered, and as an example explicit expressions are obtained for the case of a two-component amorphous solid for the frequencies of the acoustical and optical modes and for the longitudinal and transverse velocities of sound. The damping is investigated

  13. Development of In Vitro-In Vivo Correlation for Amorphous Solid Dispersion Immediate-Release Suvorexant Tablets and Application to Clinically Relevant Dissolution Specifications and In-Process Controls.

    Science.gov (United States)

    Kesisoglou, Filippos; Hermans, Andre; Neu, Colleen; Yee, Ka Lai; Palcza, John; Miller, Jessica

    2015-09-01

    Although in vitro-in vivo correlations (IVIVCs) are commonly pursued for modified-release products, there are limited reports of successful IVIVCs for immediate-release (IR) formulations. This manuscript details the development of a Multiple Level C IVIVC for the amorphous solid dispersion formulation of suvorexant, a BCS class II compound, and its application to establishing dissolution specifications and in-process controls. Four different 40 mg batches were manufactured at different tablet hardnesses to produce distinct dissolution profiles. These batches were evaluated in a relative bioavailability clinical study in healthy volunteers. Although no differences were observed for the total exposure (AUC) of the different batches, a clear relationship between dissolution and Cmax was observed. A validated Multiple Level C IVIVC against Cmax was developed for the 10, 15, 20, 30, and 45 min dissolution time points and the tablet disintegration time. The relationship established between tablet tensile strength and dissolution was subsequently used to inform suitable tablet hardness ranges within acceptable Cmax limits. This is the first published report for a validated Multiple Level C IVIVC for an IR solid dispersion formulation demonstrating how this approach can facilitate Quality by Design in formulation development and help toward clinically relevant specifications and in-process controls. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Effect of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of amorphous solid dispersions.

    Science.gov (United States)

    Sun, Weiwei; Pan, Baoliang

    2017-06-15

    This study investigates the effects of micro-environment modification and polymer type on the in-vitro dissolution behavior and in-vivo performance of micro-environment pH modifying solid dispersions (pH M -SD) for the poorly water-soluble model drug Toltrazuril (TOL). Various pH M -SDs were prepared using Ca(OH) 2 as a pH-modifier in hydrophilic polymers, including polyethylene glycol 6000 (PEG6000), polyvinylpyrrolidone k30 (PVPk30) and hydroxypropyl methylcellulose (HPMC). Based on the results of physicochemical characterizations and in-vitro dissolution testing, the representative ternary (Ca(OH) 2 :TOL:PEG6000/HPMC/PVPk30=1:8:24, w/w/w) and binary (TOL:PVPk30=1:3, w/w) solid dispersions were selected and optimized to perform in-vivo pharmacokinetic study. The micro-environment pH modification improved the in-vitro water-solubility and in-vivo bioavailability of parent drug TOL. Furthermore, the addition of alkalizers not only enhanced the release and absorption of prototype drug, but also promoted the generation of active metabolites, including toltrazuril sulfoxide (TOLSO) and toltrazuril sulfone (TOLSO 2 ). The in-vitro dissolution profiles and in-vivo absorption, distribution and metabolism behaviors of the pH M -SDs varied with polymer type. Moreover, in-vivo bioavailability of three active pharmaceutical ingredients increased with an increase in in-vitro dissolution rates of the drug from the pH M -SDs prepared with various polymers. Therefore, a non-sink in-vitro dissolution method can be used to predict the in-vivo performance of pH M -SDs formulated with various polymers with trend consistency. In-vitro and in-vivo screening procedures revealed that the pH M -SD composed of Ca(OH) 2 , TOL and PVPk30 at a weight ratio of 1:8:24, of which the safety was adequately proved via histopathological examination, may be a promising candidate for providing better clinical outcomes. Copyright © 2017. Published by Elsevier B.V.

  15. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2015-07-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  16. DEVELOPMENT OF SUSTAINED RELEASE TABLETS CONTAINING SOLID DISPERSIONS OF BACLOFEN

    Directory of Open Access Journals (Sweden)

    K. H. Janardhana

    2013-12-01

    Full Text Available Sustained release tablets containing solid dispersions granules of a poorly water soluble drug were prepared to investigate the controlled release of the drug. Baclofen was chosen because of its poor water solubility and short elimination half-life. Poloxamer 188 and PEG 6000 were used as solid dispersion carrier. Free flowing solid dispersion granules were prepared by adsorbing the melt of the drug and carriers onto the surface of an adsorbent, Carbopol 934P followed by direct compression with HPMC K4M and HPMC K100 to obtain an solid dispersion loaded sustained release tablets. FTIR studies confirmed that the compatibility of drug and carriers. Differential scanning calorimetry (DSC and X-ray diffraction (XRD revealed partially amorphous structures of the drug in solid dispersion granules. The solid dispersion granules dissolved completely within 30 min, which was much faster than that of pure drug baclofen. The sustained release of baclofen from the solid dispersion containing tablet was achieved for 2 h in gastric fluid (pH 1.2 and for up to 10 h in intestinal fluid (pH 6.8. A combination of solid dispersion techniques using adsorption and sustained release concepts is a promising approach to control the release rate of poorly water-soluble drugs.

  17. Clozapine-carboxylic acid plasticized co-amorphous dispersions: Preparation, characterization and solution stability evaluation

    Directory of Open Access Journals (Sweden)

    Ali Ahmed Mahmoud Abdelhaleem

    2015-06-01

    Full Text Available This study addressed the possibility of forming of co-amorphous systems between clozapine (CZ and various carboxylic acid plasticizers (CAPs. The aim was to improve the solubility and oral bioavailability of clozapine. Co-amorphous dispersions were prepared using modified solvent evaporation methodology at drug/plasticizer stoichiometric ratios of 1:1, 1:1.5 and 1:2. Solid state characterization was performed using differential scanning calorimetry, X-ray diffraction and infra red spectroscopy. Highly soluble homogeneous co-amorphous dispersions were formed between clozapine and CAPs via hydrogen bonding. The co-amorphous dispersions formed with tartaric acid (1:2 showed the highest dissolution percentage (> 95 % in 20 minutes compared to pure crystalline CZ (56 %. Highly stable solutions were obtained from co-amorphous CZ-citric and CZ-tartaric acid at 1:1.5 molar ratio. The prepared dispersions suggest the possibility of peroral or sublingual administration of highly soluble clozapine at a reduced dose with the great chance to bypass the first pass metabolism.

  18. Structural diversity of solid dispersions of acetylsalicylic acid as seen by solid-state NMR.

    Science.gov (United States)

    Policianova, Olivia; Brus, Jiri; Hruby, Martin; Urbanova, Martina; Zhigunov, Alexander; Kredatusova, Jana; Kobera, Libor

    2014-02-03

    Solid dispersions of active pharmaceutical ingredients are of increasing interest due to their versatile use. In the present study polyvinylpyrrolidone (PVP), poly[N-(2-hydroxypropyl)-metacrylamide] (pHPMA), poly(2-ethyl-2-oxazoline) (PEOx), and polyethylene glycol (PEG), each in three Mw, were used to demonstrate structural diversity of solid dispersions. Acetylsalicylic acid (ASA) was used as a model drug. Four distinct types of the solid dispersions of ASA were created using a freeze-drying method: (i) crystalline solid dispersions containing nanocrystalline ASA in a crystalline PEG matrix; (ii) amorphous glass suspensions with large ASA crystallites embedded in amorphous pHPMA; (iii) solid solutions with molecularly dispersed ASA in rigid amorphous PVP; and (iv) nanoheterogeneous solid solutions/suspensions containing nanosized ASA clusters dispersed in a semiflexible matrix of PEOx. The obtained structural data confirmed that the type of solid dispersion can be primarily controlled by the chemical constitutions of the applied polymers, while the molecular weight of the polymers had no detectable impact. The molecular structure of the prepared dispersions was characterized using solid-state NMR, wide-angle X-ray scattering (WAXS), and differential scanning calorimetry (DSC). By applying various (1)H-(13)C and (1)H-(1)H correlation experiments combined with T1((1)H) and T1ρ((1)H) relaxation data, the extent of the molecular mixing was determined over a wide range of distances, from intimate intermolecular contacts (0.1-0.5 nm) up to the phase-separated nanodomains reaching ca. 500 nm. Hydrogen-bond interactions between ASA and polymers were probed by the analysis of (13)C and (15)N CP/MAS NMR spectra combined with the measurements of (1)H-(15)N dipolar profiles. Overall potentialities and limitations of individual experimental techniques were thoroughly evaluated.

  19. Advantageous Solubility-Permeability Interplay When Using Amorphous Solid Dispersion (ASD) Formulation for the BCS Class IV P-gp Substrate Rifaximin: Simultaneous Increase of Both the Solubility and the Permeability.

    Science.gov (United States)

    Beig, Avital; Fine-Shamir, Noa; Lindley, David; Miller, Jonathan M; Dahan, Arik

    2017-05-01

    Rifaximin is a BCS class IV (low-solubility, low-permeability) drug and also a P-gp substrate. The aims of this work were to assess the efficiency of different rifaximin amorphous solid dispersion (ASDs) formulations in achieving and maintaining supersaturation and to investigate the consequent solubility-permeability interplay. Spray-dried rifaximin ASDs were prepared with different hydrophilic polymers and their ability to achieve and maintain supersaturation was assessed. Then, rifaximin's apparent intestinal permeability was investigated as a function of increasing supersaturation both in vitro using the parallel artificial membrane permeability assay (PAMPA) and in vivo using the single-pass rat intestinal perfusion (SPIP) model. The efficiency of the different ASDs to achieve and maintain supersaturation of rifaximin was found to be highly polymer dependent, and the copovidone/HPC-SL formulation was found to be superior to the other two, allowing supersaturation of 200× that of the crystalline solubility for 20 h. In vitro, rifaximin flux was increased and the apparent permeability was constant as a function of increasing supersaturation level. In vivo, on the other hand, absorption rate coefficient (k a ) was first constant as a function of increasing supersaturation, but at 250×, the crystalline solubility k a was doubled, similar to the k a in the presence of the strong P-gp inhibitor GF120918. In conclusion, a new and favorable nature of solubility-permeability interplay was revealed in this work: delivering high supersaturation level of the BCS class IV drug rifaximin via ASD, thereby saturating the drugs' P-gp-mediated efflux transport, led to the favorable unique win-win situation, where both the solubility and the permeability increased simultaneously.

  20. Characterization during storage and dissolution of Solid dispersions containing furosemide and hydroxypropyl methylcellulose

    DEFF Research Database (Denmark)

    Nielsen, Line Hagner; Rades, T.; Müllertz, A.

    2013-01-01

    Solid dispersions containing furosemide and various amounts of hydroxypropyl methylcellulose (HPMC) were prepared by spray drying to investigate if the physical stability of amorphous furosemide during storage and dissolution could be improved by formulating the drug as a solid dispersion. All...

  1. Dynamics of viscoplastic deformation in amorphous solids

    International Nuclear Information System (INIS)

    Falk, M.L.; Langer, J.S.

    1998-01-01

    We propose a dynamical theory of low-temperature shear deformation in amorphous solids. Our analysis is based on molecular-dynamics simulations of a two-dimensional, two-component noncrystalline system. These numerical simulations reveal behavior typical of metallic glasses and other viscoplastic materials, specifically, reversible elastic deformation at small applied stresses, irreversible plastic deformation at larger stresses, a stress threshold above which unbounded plastic flow occurs, and a strong dependence of the state of the system on the history of past deformations. Microscopic observations suggest that a dynamically complete description of the macroscopic state of this deforming body requires specifying, in addition to stress and strain, certain average features of a population of two-state shear transformation zones. Our introduction of these state variables into the constitutive equations for this system is an extension of earlier models of creep in metallic glasses. In the treatment presented here, we specialize to temperatures far below the glass transition and postulate that irreversible motions are governed by local entropic fluctuations in the volumes of the transformation zones. In most respects, our theory is in good quantitative agreement with the rich variety of phenomena seen in the simulations. copyright 1998 The American Physical Society

  2. Solid phase epitaxy of amorphous silicon carbide: Ion fluence dependence

    International Nuclear Information System (INIS)

    Bae, I.-T.; Ishimaru, Manabu; Hirotsu, Yoshihiko; Sickafus, Kurt E.

    2004-01-01

    We have investigated the effect of radiation damage and impurity concentration on solid phase epitaxial growth of amorphous silicon carbide (SiC) as well as microstructures of recrystallized layer using transmission electron microscopy. Single crystals of 6H-SiC with (0001) orientation were irradiated with 150 keV Xe ions to fluences of 10 15 and 10 16 /cm 2 , followed by annealing at 890 deg. C. Full epitaxial recrystallization took place in a specimen implanted with 10 15 Xe ions, while retardation of recrystallization was observed in a specimen implanted with 10 16 /cm 2 Xe ions. Atomic pair-distribution function analyses and energy dispersive x-ray spectroscopy results suggested that the retardation of recrystallization of the 10 16 Xe/cm 2 implanted sample is attributed to the difference in amorphous structures between the 10 15 and 10 16 Xe/cm 2 implanted samples, i.e., more chemically disordered atomistic structure and higher Xe impurity concentration in the 10 16 Xe/cm 2 implanted sample

  3. Local order and magnetism of amorphous and disordered solids

    International Nuclear Information System (INIS)

    Friedt, J.M.

    1985-01-01

    Some topics related with the magnetic properties and local order in amorphous and disordered solids studied by Moessbauer spectroscopy, EXAFS, static and dynamical susceptibilities are presented. (L.C.) [pt

  4. Nonaffinity in amorphous solids close to the jamming transition

    Directory of Open Access Journals (Sweden)

    Arévalo Roberto

    2017-01-01

    Full Text Available Nonaffinity is known to be an integral part of the response of amorphous solids. Its role is particularly relevant in particulate systems close to their jamming transition, where it dominates the elastic response. Thus, to determine the elastic properties of amorphous solids it is essential to rationalize the features of their nonaffine response. Via numerical simulations we investigate the relation between the non affine response and the vibrational properties of model amorphous materials. We show that, contrary to previous speculations, modes below the Boson peak are those mostly responsible for the nonaffine response.

  5. Enhancing the bioavailability of magnolol in rabbits using melting solid dispersion with polyvinylpyrrolidone.

    Science.gov (United States)

    Lin, Shiuan-Pey; Hou, Yu-Chi; Liao, Tzu-Yun; Tsai, Shang-Yuan

    2014-03-01

    Preparation of magnolol-loaded amorphous solid dispersion was investigated for improving the bioavailability. A solid dispersion of magnolol was prepared with polyvinylpyrrolidone K-30 (PVP) by melting method, and the physical properties were characterized by using differential scanning calorimetry, powder X-ray diffractometry, Fourier transformation-infrared spectroscopy and scanning electron microscope. In addition, dissolution test was also performed. Subsequently, the bioavailability of magnolol pure compound, its physical mixture and solid dispersion were compared in rabbits. The blood samples withdrawn via marginal ear vein at specific time points were assayed by HPLC method. Oral administration of the solid dispersion of magnolol with PVP significantly increased the systemic exposures of magnolol and magnolol sulfates/glucuronides by 80.1% and 142.8%, respectively, compared to those given with magnolol pure compound. Magnolol-loaded amorphous solid dispersion with PVP has demonstrated enhanced bioavailability of magnolol in rabbits.

  6. Structural insight into the physical stability of amorphous Simvastatin dispersed in pHPMA: enhanced dynamics and local clustering as evidenced by solid-state NMR and Raman spectroscopy

    Czech Academy of Sciences Publication Activity Database

    Urbanová, Martina; Šturcová, Adriana; Kredatusová, Jana; Brus, Jiří

    2015-01-01

    Roč. 478, č. 2 (2015), s. 464-475 ISSN 0378-5173 R&D Projects: GA ČR(CZ) GA14-03636S; GA MŠk(CZ) LD14010 Grant - others:European Commission(XE) COST Action MP1202 HINT Institutional support: RVO:61389013 Keywords : solid dispersions * simvastatin * pharmaceuticals Subject RIV: CD - Macromolecular Chemistry Impact factor: 3.994, year: 2015

  7. Radiation damage in amorphous solids - a computer simulation

    International Nuclear Information System (INIS)

    Chaki, T.K.; Li, J.C.M.

    1984-01-01

    It is known for crystalline materials that injection of high energy atoms introduces point defects. The nature of defects is not known for amorphous solids. So a molecular dynamic simulation of radiation damage in an amorphous metal was carried out. An amorphous structure of 685 atoms with periodic boundary conditions in all 3 dimensions was equilibrated first. Then one atom on the surface was given a high initial velocity so it was injected inward. Radial temperature distribution around the line of injection was calculated as a function of time. Void distribution and its evolution with time in the direction of injection was calculated by counting the atomic centers in thin slabs perpendicular to the line of injection. The swelling of the whole solid was calculated also. Some results are compared with experiments

  8. Influence of waste solid on nuclide dispersal

    International Nuclear Information System (INIS)

    Seitz, M.G.; Steindler, M.J.

    1981-01-01

    The method most often considered for permanent disposal of radioactive waste is to incorporate the waste into a solid, which is then placed in a geologic formation. The solid is made of waste and nonradioactive additives, with the formulation selected to produce a durable solid that will minimize the potential for dispersal of the radionuclides. Leach rates of radionuclides incorporated in the solid waste indicate the quantity of radioactivity available for dispersal at any time; but leach rates of stable constituents can be just as important to radionuclide dispersal by groundwater. The constituents of the solid will perturb the chemical character of the groundwater and, thereby, profoundly affect the interaction of radionuclides with the geologic medium. An explicit example of how the solid waste can affect radionuclide dispersal is illustrated by the results of experiments that measure cesium adsorption in the presence of rubidium. The experiments were performed with granulated oolitic limestone that absorbed cesium from groundwater solutions to which various concentrations of stable rubidium chloride had been added. The results are expressed as partition coefficients. Large coefficients indicate strong adsorption by the rock and, hence, slow migration. The partition coefficient for cesium decreases as the rubidium concentration in solution is increased. Because the coeficient for cesium depends on the amount of rubidium in solution, it will depend on the leach rate of rubidium from the solid. Rubidium has no radionuclides of concern for long-term isolation of nuclear waste, so its leach rate from a waste solid is rarely ever reported

  9. Microstructural model for the plasticity of amorphous solids

    NARCIS (Netherlands)

    Hütter, M.; Breemen, van L.C.A.

    2012-01-01

    Based on the concept of localized shear transformation zones (STZ), a thermodynamically consistent model for the viscoplastic deformation of amorphous solids is developed. The approach consists of a dynamic description of macroscopic viscoplasticity that is enriched by the evolution of number

  10. Radiation damage in an amorphous Lennard-Jones solid

    International Nuclear Information System (INIS)

    Chaki, T.K.; Li, J.C.M.

    1985-01-01

    A molecular-dynamics simulation of radiation damage in an amorphous Lennard-Jones solid has been undertaken. A three-dimensional structure of 685 atoms with periodic boundary conditions was used. An atom was injected inward from the middle of one surface, and as it lost its energy its velocity and position were recorded. The temperature profile around the injection direction was also calculated. The amorphous structure was examined before and after irradiation by calculating the volume distribution of the Voronoi polyhedra and its time evolution. The production of vacancies and interstitials was observed. The interstitials were found to disappear rapidly, and the vacancies slowly. (author)

  11. Development and Physicochemical Characterization of Sirolimus Solid Dispersions Prepared by Solvent Evaporation Method

    Directory of Open Access Journals (Sweden)

    Shahram Emami

    2014-12-01

    Full Text Available Purpose: The aim of the present investigation was preparation and characterization of sirolimus solid dispersions by solvent evaporation technique to improve its dissolution properties. Methods: Polyvinylpyrrolidone (PVP, Poloxamer 188 and Cremophore RH40 were used to prepare the solid dispersions of sirolimus. In vitro dissolution study using USP type I apparatus, were performed in distilled water (containing SLS 0.4% for pure sirolimus, physical mixtures, Rapamune and prepared solid dispersions. The characterization of solid dispersions was performed using Fourier Transform Infrared (FTIR Spectroscopy and Differential Scanning Calorimetry (DSC. Results: More than 75% of sirolimus was released within 30 minutes from all prepared solid dispersions. The dissolution rate of all prepared solid dispersion powders were more than physical mixtures. The absence of sirolimus peak in the DSC spectrum of solid dispersions indicated the conversion of crystalline form of sirolimus into amorphous form. The results from FT-IR spectroscopy showed that there was no significant change in the FT-IR spectrum of solid dispersions indicating absence of well-defined interaction between drug and carriers. Conclusion: It was concluded that solid dispersion method, using PVP, Poloxamer 188 and Cremophore RH40 can improve dissolution rate of sirolimus.

  12. Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media.

    Science.gov (United States)

    Alhayali, Amani; Tavellin, Staffan; Velaga, Sitaram

    2017-01-01

    The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25 °C and 37 °C) were investigated in this work. Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions. All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25 °C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD) solid dispersions and supersaturation was maintained. However, at 37 °C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures. Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25 °C may not predict the supersaturation behavior at physiologically relevant temperatures.

  13. Dynamics of amorphous solids and viscous liquids

    DEFF Research Database (Denmark)

    Dyre, Jeppe

    -square displacement as function of time. The 15 publications are related to each other in the following way. P1-P7 is a continuously progressing attempt to explain the AC properties of extremely disordered solids (with P2 as a digression). P8 discusses a simple model for viscous liquids and the glass transition. In P...... with the title "Viscous Liquids and the Glass Transition" reviews and comments P8-P10. In P8 from 1987 a simple model for the glass transition is proposed in which there is only one relevant degree of freedom, the potential energy of a region in the liquid. The model was originally constructed to explain the non......This thesis consists of fifteen publications (P1-P15) published between 1987 and 1996 and a summary. In this abstract an overview of the main results is given by following the summary's three Chapters. The first Chapter with the title "AC Conduction in Disordered Solids" reviews and comments P1-P7...

  14. Characterization and physical stability of spray dried solid dispersions of probucol and PVP-K30

    DEFF Research Database (Denmark)

    Thybo, Pia; Pedersen, Betty L; Hovgaard, Lars

    2008-01-01

    The main purpose of this study was to obtain stable, well-characterized solid dispersions (SDs) of amorphous probucol and polyvinylpyrrolidone K-30 (PVP-K30) with improved dissolution rates. A secondary aim was to investigate the flow-through dissolution method for in-vitro dissolution measuremen...

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

    Science.gov (United States)

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

    2013-09-01

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

  16. Physicochemical characterization of tacrolimus-loaded solid dispersion with sodium carboxylmethyl cellulose and sodium lauryl sulfate.

    Science.gov (United States)

    Park, Young-Joon; Ryu, Dong-Sung; Li, Dong Xun; Quan, Qi Zhe; Oh, Dong Hoon; Kim, Jong Oh; Seo, Youn Gee; Lee, Young-Im; Yong, Chul Soon; Woo, Jong Soo; Choi, Han-Gon

    2009-06-01

    To develop a novel tacrolimus-loaded solid dispersion with improved solubility, various solid dispersions were prepared with various ratios of water, sodium lauryl sulfate, citric acid and carboxylmethylcellulose-Na using spray drying technique. The physicochemical properties of solid dispersions were investigated using scanning electron microscopy, differential scanning calorimetery and powder X-ray diffraction. Furthermore, their solubility and dissolution were evaluated compared to drug powder. The solid dispersion at the tacrolimus/CMC-Na/sodium lauryl sulfate/citric acid ratio of 3/24/3/0.2 significantly improved the drug solubility and dissolution compared to powder. The scanning electron microscopy result suggested that carriers might be attached to the surface of drug in this solid dispersion. Unlike traditional solid dispersion systems, the crystal form of drug in this solid dispersion could not be converted to amorphous form, which was confirmed by the analysis of DSC and powder X-ray diffraction. Thus, the solid dispersion system with water, sodium lauryl sulfate, citric acid and CMC-Na should be a potential candidate for delivering a poorly water-soluble tacrolimus with enhanced solubility and no convertible crystalline.

  17. Development of solid dispersion systems of dapivirine to enhance its solubility.

    Science.gov (United States)

    Gorajana, Adinarayana; Ying, Chan Chiew; Shuang, Yeen; Fong, Pooi; Tan, Zhi; Gupta, Jyoti; Talekar, Meghna; Sharma, Manisha; Garg, Sanjay

    2013-06-01

    Dapivirine, formerly known as TMC 120, is a poorly-water soluble anti-HIV drug, currently being developed as a vaginal microbicide. The clinical use of this drug has been limited due to its poor solubility. The aim of this study was to design solid dispersion systems of Dapivirine to improve its solubility. Solid dispersions were prepared by solvent and fusion methods. Dapivirine release from the solid dispersion system was determined by conducting in-vitro dissolution studies. The physicochemical characteristics of the drug and its formulation were studied using Differential Scanning Calorimetry (DSC), powder X-ray Diffraction (XRD), Fourier-transform Infrared Spectroscopy (FTIR) and Scanning Electron Microscopy (SEM). A significant improvement in drug dissolution rate was observed with the solid dispersion systems. XRD, SEM and DSC results indicated the transformation of pure Dapivirine which exists in crystalline form into an amorphous form in selected solid dispersion formulations. FTIR and HPLC analysis confirmed the absence of drug-excipient interactions. Solid dispersion systems can be used to improve the dissolution rate of Dapivirine. This improvement could be attributed to the reduction or absence of drug crystallinity, existence of drug particles in an amorphous form and improved wettability of the drug.

  18. Development and characterization of nifedipine-amino methacrylate copolymer solid dispersion powders with various adsorbents

    Directory of Open Access Journals (Sweden)

    Yotsanan Weerapol

    2017-07-01

    Full Text Available Solid dispersions of nifedipine (NDP, a poorly water-soluble drug, and amino methacrylate copolymer (AMCP with aid of adsorbent, that is, fumed silica, talcum, calcium carbonate, titanium dioxide, and mesoporous silica from rice husks (SRH, were prepared by solvent method. The physicochemical properties of solid dispersions, compared to their physical mixtures, were determined using powder X-ray diffractometry (PXRD and differential scanning calorimetry (DSC. The surface morphology of the prepared solid dispersions was examined by scanning electron microscopy (SEM. The dissolution of NDP from solid dispersions was compared to NDP powders. The effect of adsorbent type on NDP dissolution was also examined. The dissolution of NDP increased with the ratio of NDP:AMCP:adsorbent of 1:4:1 when compared to the other formulations. As indicated from PXRD patterns, DSC thermograms and SEM images, NDP was molecularly dispersed within polymer carrier or in an amorphous form, which confirmed the better dissolution of solid dispersions. Solid dispersions containing SRH provided the highest NDP dissolution, due to a porous nature of SRH, allowing dissolved drug to fill in the pores and consequently dissolve in the medium. The results suggested that solid dispersions containing adsorbents (SRH in particular demonstrated improved dissolution of poorly water-soluble drug when compared to NDP powder.

  19. REVIEW ON SPRAY DRIED SOLID DISPERSION

    OpenAIRE

    Zambre Radhika Ashok, Dr. Shendge R.S, Narode Pravin Ravindra, Sonawane Swapnil Prakash

    2018-01-01

    The drug solubility is the most challenging aspect for the formulation development. The poorly soluble drug has poor dissolution and absorption of drug. The low aqueous solubility of drug is required to formulate the drug into more soluble and hence bioavailable drug product. The different technique is being used to enhance the solubility of poorly water soluble drugs. Spray dried solid dispersion of drug is one of the most widely used technology to enhance the solubility of the poorly water ...

  20. Degradation of L-Ascorbic Acid in the Amorphous Solid State.

    Science.gov (United States)

    Sanchez, Juan O; Ismail, Yahya; Christina, Belinda; Mauer, Lisa J

    2018-03-01

    Ascorbic acid degradation in amorphous solid dispersions was compared to its degradation in the crystalline state. Physical blends and lyophiles of ascorbic acid and polymers (pectins and polyvinylpyrrolidone [PVP]) were prepared initially at 50:50 (w/w), with further studies using the polymer that best inhibited ascorbic acid crystallization in the lyophiles in 14 vitamin : PVP ratios. Samples were stored in controlled environments (25 to 60 °C, 0% to 23% RH) for 1 mo and analyzed periodically to track the physical appearance, change in moisture content, physical state (powder x-ray diffraction and polarized light microscopy), and vitamin loss (high performance liquid chromatography) over time. The glass transition temperatures of select samples were determined using differential scanning calorimetry, and moisture sorption profiles were generated. Ascorbic acid in the amorphous form, even in the glassy amorphous state, was more labile than in the crystalline form in some formulations at the highest storage temperature. Lyophiles stored at 25 and 40 °C and those in which ascorbic acid had crystallized at 60 °C (≥70% ascorbic acid : PVP) had no significant difference in vitamin loss (P > 0.05) relative to physical blend controls, and the length of storage had little effect. At 60 °C, amorphous ascorbic acid lyophiles (≤60% ascorbic acid : PVP) lost significantly more vitamin (P vitamin loss significantly increased over time. In these lyophiles, vitamin degradation also significantly increased (P vitamins are naturally present or added at low concentrations and production practices may promote amorphization of the vitamin. Vitamin C is one of the most unstable vitamins in foods. This study documents that amorphous ascorbic acid is less stable than crystalline ascorbic acid in some environments (for example, higher temperatures within 1 wk), especially when the vitamin is present at low concentrations in a product. These findings increase the understanding of

  1. Both solubility and chemical stability of curcumin are enhanced by solid dispersion in cellulose derivative matrices.

    Science.gov (United States)

    Li, Bin; Konecke, Stephanie; Wegiel, Lindsay A; Taylor, Lynne S; Edgar, Kevin J

    2013-10-15

    Amorphous solid dispersions (ASD) of curcumin (Cur) in cellulose derivative matrices, hydroxypropylmethylcellulose acetate succinate (HPMCAS), carboxymethylcellulose acetate butyrate (CMCAB), and cellulose acetate adipate propionate (CAAdP) were prepared in order to investigate the structure-property relationship and identify polymer properties necessary to effectively increase Cur aqueous solution concentration. XRD results indicated that all investigated solid dispersions were amorphous, even at a 9:1 Cur:polymer ratio. Both stability against crystallization and Cur solution concentration from these ASDs were significantly higher than those from physical mixtures and crystalline Cur. Remarkably, curcumin was also stabilized against chemical degradation in solution. Chemical stabilization was polymer-dependent, with stabilization in CAAdP>CMCAB>HPMCAS>PVP, while matrices enhanced solution concentration as PVP>HPMCAS>CMCAB≈CAAdP. HPMCAS/Cur dispersions have useful combinations of pH-triggered release profile, chemical stabilization, and strong enhancement of Cur solution concentration. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Ion bombardment induced ripple topography on amorphous solids

    International Nuclear Information System (INIS)

    Carter, G.; Nobes, M.J.; Paton, F.; Williams, J.S.

    1977-01-01

    Earlier studies of the ion bombardment induced ripple morphology on the surfaces of amorphous solids when compared with geomorphological effects are shown to possess many similar features. The present study, with 40 keV Ar + ion bombarded Si suggests that analogies are incomplete, however, and that greater similarities with the process of macroscopic sandblasting (corrosion) exist. It is shown that the genesis of wave like structures on Si is from isolated features, which have the appearance of ripple trains, which are faceted. It is suggested that these features result from particle flux enhancement processes near surface dimples generated by stress induced surface lifting. (author)

  3. Avalanche size scaling in sheared three-dimensional amorphous solid

    DEFF Research Database (Denmark)

    Bailey, Nicholas; Schiøtz, Jakob; Lemaître, A.

    2007-01-01

    We study the statistics of plastic rearrangement events in a simulated amorphous solid at T=0. Events are characterized by the energy release and the "slip volume", the product of plastic strain and system volume. Their distributions for a given system size L appear to be exponential......, but a characteristic event size cannot be inferred, because the mean values of these quantities increase as L-alpha with alpha similar to 3/2. In contrast with results obtained in 2D models, we do not see simply connected avalanches. The exponent suggests a fractal shape of the avalanches, which is also evidenced...

  4. Hydration of ammonia, methylamine, and methanol in amorphous solid water

    Science.gov (United States)

    Souda, Ryutaro

    2016-02-01

    Interactions of polar protic molecules with amorphous solid water (ASW) have been investigated using temperature-programmed desorption and time-of-flight secondary ion mass spectrometry. The ammonia and methylamine are incorporated into the interior of porous ASW films. They are caged by water molecules and are released during water crystallization. In contrast, the methanol-water interaction is not influenced by pores of ASW. The methanol additives tend to survive water crystallization and are released during ASW film evaporation. The hydration of n-hexane in ASW is influenced significantly by methanol additives because n-hexane is accommodated in a methanol-induced hydration shell.

  5. Optimising Drug Solubilisation in Amorphous Polymer Dispersions: Rational Selection of Hot-melt Extrusion Processing Parameters.

    Science.gov (United States)

    Li, Shu; Tian, Yiwei; Jones, David S; Andrews, Gavin P

    2016-02-01

    The aim of this article was to construct a T-ϕ phase diagram for a model drug (FD) and amorphous polymer (Eudragit® EPO) and to use this information to understand the impact of how temperature-composition coordinates influenced the final properties of the extrudate. Defining process boundaries and understanding drug solubility in polymeric carriers is of utmost importance and will help in the successful manufacture of new delivery platforms for BCS class II drugs. Physically mixed felodipine (FD)-Eudragit(®) EPO (EPO) binary mixtures with pre-determined weight fractions were analysed using DSC to measure the endset of melting and glass transition temperature. Extrudates of 10 wt% FD-EPO were processed using temperatures (110°C, 126°C, 140°C and 150°C) selected from the temperature-composition (T-ϕ) phase diagrams and processing screw speed of 20, 100 and 200rpm. Extrudates were characterised using powder X-ray diffraction (PXRD), optical, polarised light and Raman microscopy. To ensure formation of a binary amorphous drug dispersion (ADD) at a specific composition, HME processing temperatures should at least be equal to, or exceed, the corresponding temperature value on the liquid-solid curve in a F-H T-ϕ phase diagram. If extruded between the spinodal and liquid-solid curve, the lack of thermodynamic forces to attain complete drug amorphisation may be compensated for through the use of an increased screw speed. Constructing F-H T-ϕ phase diagrams are valuable not only in the understanding drug-polymer miscibility behaviour but also in rationalising the selection of important processing parameters for HME to ensure miscibility of drug and polymer.

  6. Criticality in the Approach to Failure in Amorphous Solids

    Science.gov (United States)

    Lin, Jie; Gueudré, Thomas; Rosso, Alberto; Wyart, Matthieu

    2015-10-01

    Failure of amorphous solids is fundamental to various phenomena, including landslides and earthquakes. Recent experiments indicate that highly plastic regions form elongated structures that are especially apparent near the maximal shear stress Σmax where failure occurs. This observation suggested that Σmax acts as a critical point where the length scale of those structures diverges, possibly causing macroscopic transient shear bands. Here, we argue instead that the entire solid phase (Σ system-spanning events, and that their magnitude diverges at Σmax independently of the presence of shear bands. We relate the statistics and fractal properties of these rearrangements to an exponent θ that captures the stability of the material, which is observed to vary continuously with stress, and we confirm our predictions in elastoplastic models.

  7. Amorphous surface layer versus transient amorphous precursor phase in bone - A case study investigated by solid-state NMR spectroscopy.

    Science.gov (United States)

    Von Euw, Stanislas; Ajili, Widad; Chan-Chang, Tsou-Hsi-Camille; Delices, Annette; Laurent, Guillaume; Babonneau, Florence; Nassif, Nadine; Azaïs, Thierry

    2017-09-01

    The presence of an amorphous surface layer that coats a crystalline core has been proposed for many biominerals, including bone mineral. In parallel, transient amorphous precursor phases have been proposed in various biomineralization processes, including bone biomineralization. Here we propose a methodology to investigate the origin of these amorphous environments taking the bone tissue as a key example. This study relies on the investigation of a bone tissue sample and its comparison with synthetic calcium phosphate samples, including a stoichiometric apatite, an amorphous calcium phosphate sample, and two different biomimetic apatites. To reveal if the amorphous environments in bone originate from an amorphous surface layer or a transient amorphous precursor phase, a combined solid-state nuclear magnetic resonance (NMR) experiment has been used. The latter consists of a double cross polarization 1 H→ 31 P→ 1 H pulse sequence followed by a 1 H magnetization exchange pulse sequence. The presence of an amorphous surface layer has been investigated through the study of the biomimetic apatites; while the presence of a transient amorphous precursor phase in the form of amorphous calcium phosphate particles has been mimicked with the help of a physical mixture of stoichiometric apatite and amorphous calcium phosphate. The NMR results show that the amorphous and the crystalline environments detected in our bone tissue sample belong to the same particle. The presence of an amorphous surface layer that coats the apatitic core of bone apatite particles has been unambiguously confirmed, and it is certain that this amorphous surface layer has strong implication on bone tissue biogenesis and regeneration. Questions still persist on the structural organization of bone and biomimetic apatites. The existing model proposes a core/shell structure, with an amorphous surface layer coating a crystalline bulk. The accuracy of this model is still debated because amorphous calcium

  8. Crosslinked hydrogels?a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

    OpenAIRE

    Sun, Dajun D.; Lee, Ping I.

    2014-01-01

    Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a ...

  9. Fundamental aspects of solid dispersion technology for poorly soluble drugs

    Directory of Open Access Journals (Sweden)

    Yanbin Huang

    2014-02-01

    Full Text Available The solid dispersion has become an established solubilization technology for poorly water soluble drugs. Since a solid dispersion is basically a drug–polymer two-component system, the drug–polymer interaction is the determining factor in its design and performance. In this review, we summarize our current understanding of solid dispersions both in the solid state and in dissolution, emphasizing the fundamental aspects of this important technology.

  10. Solid State Characterization of Commercial Crystalline and Amorphous Atorvastatin Calcium Samples

    OpenAIRE

    Shete, Ganesh; Puri, Vibha; Kumar, Lokesh; Bansal, Arvind K.

    2010-01-01

    Atorvastatin calcium (ATC), an anti-lipid BCS class II drug, is marketed in crystalline and amorphous solid forms. The objective of this study was to perform solid state characterization of commercial crystalline and amorphous ATC drug samples available in the Indian market. Six samples each of crystalline and amorphous ATC were characterized using X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis, Karl Fisher titrimetry, microscopy (hot s...

  11. Solid state synthesis of water-dispersible silicon nanoparticles from silica nanoparticles

    International Nuclear Information System (INIS)

    Kravitz, Keren; Kamyshny, Alexander; Gedanken, Aharon; Magdassi, Shlomo

    2010-01-01

    A solid state synthesis for obtaining nanocrystalline silicon was performed by high temperature reduction of commercial amorphous nanosilica with magnesium powder. The obtained silicon powder contains crystalline silicon phase with lattice spacings characteristic of diamond cubic structure (according to high resolution TEM), and an amorphous phase. In 29 Si CP MAS NMR a broad multicomponent peak corresponding to silicon is located at -61.28 to -69.45 ppm, i.e. between the peaks characteristic of amorphous and crystalline Si. The powder has displayed red luminescence while excited under UV illumination, due to quantum confinement within the nanocrystals. The silicon nanopowder was successfully dispersed in water containing poly(vinyl alcohol) as a stabilizing agent. The obtained dispersion was also characterized by red photoluminescence with a band maximum at 710 nm, thus enabling future functional coating applications. - Graphical abstract: High temperature reduction of amorphous nanosilica with magnesium powder results in the formation of powder containing crystalline silicon phase The powder displays red luminescence while excited under UV illumination, due to quantum confinement within the Si nanocrystals, and can be successfully dispersed in water containing poly(vinyl alcohol) as a stabilizing agent. The obtained dispersion was also characterized by red photoluminescence, thus enabling future functional coating applications.

  12. Resolving amorphous solid-liquid interfaces by atomic force microscopy

    International Nuclear Information System (INIS)

    Burson, Kristen M.; Gura, Leonard; Kell, Burkhard; Büchner, Christin; Lewandowski, Adrian L.; Heyde, Markus; Freund, Hans-Joachim

    2016-01-01

    Recent advancements in liquid atomic force microscopy make it an ideal technique for probing the structure of solid-liquid interfaces. Here, we present a structural study of a two-dimensional amorphous silica bilayer immersed in an aqueous solution utilizing liquid atomic force microscopy with sub-nanometer resolution. Structures show good agreement with atomically resolved ultra-high vacuum scanning tunneling microscopy images obtained on the same sample system, owing to the structural stability of the silica bilayer and the imaging clarity from the two-dimensional sample system. Pair distance histograms of ring center positions are utilized to develop quantitative metrics for structural comparison, and the physical origin of pair distance histogram peaks is addressed by direct assessment of real space structures.

  13. Solubility and dissolution performances of spray-dried solid dispersion of Efavirenz in Soluplus.

    Science.gov (United States)

    Lavra, Zênia Maria Maciel; Pereira de Santana, Davi; Ré, Maria Inês

    2017-01-01

    Efavirenz (EFV), a first-line anti-HIV drug largely used as part of antiretroviral therapies, is practically insoluble in water and belongs to BCS class II (low solubility/high permeability). The aim of this study was to improve the solubility and dissolution performances of EFV by formulating an amorphous solid dispersion of the drug in polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus ® ) using spray-drying technique. To this purpose, spray-dried dispersions of EFV in Soluplus ® at different mass ratios (1:1.25, 1:7, 1:10) were prepared and characterized using particle size measurements, SEM, XRD, DSC, FTIR and Raman microscopy mapping. Solubility and dissolution were determined in different media. Stability was studied at accelerated conditions (40 °C/75% RH) and ambient conditions for 12 months. DSC and XRD analyses confirmed the EFV amorphous state. FTIR spectroscopy analyses revealed possible drug-polymer molecular interaction. Solubility and dissolution rate of EFV was enhanced remarkably in the developed spray-dried solid dispersions, as a function of the polymer concentration. Spray-drying was concluded to be a proper technique to formulate a physically stable dispersion of amorphous EFV in Soluplus ® , when protected from moisture.

  14. Comparison of three different types of cilostazol-loaded solid dispersion: Physicochemical characterization and pharmacokinetics in rats.

    Science.gov (United States)

    Mustapha, Omer; Kim, Kyung Soo; Shafique, Shumaila; Kim, Dong Shik; Jin, Sung Giu; Seo, Youn Gee; Youn, Yu Seok; Oh, Kyung Taek; Yong, Chul Soon; Kim, Jong Oh; Choi, Han-Gon

    2017-06-01

    The aim of this research was to compare three different types of cilostazol-loaded solid dispersion system including solvent-evaporated, solvent-wetted and surface-attached solid dispersion. The effect of polymers and surfactants on the aqueous solubility of cilostazol was investigated, leading to the selection of polyvinylpyrrolidone (PVP) and sodium lauryl sulphate (SLS). Employing a spray-drying technique, numerous surface-attached, solvent-evaporated and solvent-wetted solid dispersions were prepared with various amounts PVP and SLS using water, 90% ethanol and acetone, respectively. Their physicochemical properties, solubility, dissolution and oral bioavailability in rats were assessed compared to the drug powder. Among each solid dispersion system tested, the surface-attached, solvent-evaporated and solvent-wetted solid dispersions composed of cilostazol, PVP and SLS at weight ratios of 3.0 : 0.75 : 1.5, 3.0 : 3.0 : 1.5 and 3.0 : 3.0 : 1.5, respectively, provided the highest drug solubility and dissolution. The solvent-evaporated solid dispersion gave homogeneous and very small spherical particles, in which the drug was changed to an amorphous state. In the solvent-wetted solid dispersion, the amorphous drug was attached to the polymer surface. Conversely, in the surface-attached solid dispersion, the carriers were adhered onto the surface of the unchanged crystalline drug. The solubility, dissolution and oral bioavailability were significantly increased in the order of solvent-evaporated>solvent-wetted>surface-attached>drug powder. Thus, the type of solid dispersion considerably affected the physicochemical properties, aqueous solubility and oral bioavailability. Furthermore, the cilostazol-loaded solvent-evaporated solid dispersion with the highest oral bioavailability would be actively recommended as a practical oral pharmaceutical product. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. In vitro Dissolution Studies on Solid Dispersions of Mefenamic Acid.

    Science.gov (United States)

    Rao, K R S Sambasiva; Nagabhushanam, M V; Chowdary, K P R

    2011-03-01

    Solid dispersions of mefanamic acid with a water-soluble polymer polyvinyl pyrrolidine and a super disintegrant, primojel were prepared by common solvent and solvent evaporation methods employing methanol as the solvent. The dissolution rate and dissolution efficiency of the prepared solid dispersions were evaluated in comparison to the corresponding pure drug. Solid dispersions of mefenamic acid showed a marked enhancement in dissolution rate and dissolution efficiency. At 1:4 ratio of mefenamic acid-primojel a 2.61 fold increase in the dissolution rate of mefenamic acid was observed with solid dispersion. The solid dispersions in combined carriers gave much higher rates of dissolution than super disintegrants alone. Mefanamic acid-primojel-polyvinyl pyrrolidine (1:3.2:0.8) solid dispersion gave a 4.11 fold increase in the dissolution rate of mefenamic acid. Super disintegrants alone or in combination with polyvinyl pyrrolidine could be used to enhance the dissolution rate of mefenamic acid.

  16. Amorphous drugs and dosage forms

    DEFF Research Database (Denmark)

    Grohganz, Holger; Löbmann, K.; Priemel, P.

    2013-01-01

    The transformation to an amorphous form is one of the most promising approaches to address the low solubility of drug compounds, the latter being an increasing challenge in the development of new drug candidates. However, amorphous forms are high energy solids and tend to recry stallize. New...... formulation principles are needed to ensure the stability of amorphous drug forms. The formation of solid dispersions is still the most investigated approach, but additional approaches are desirable to overcome the shortcomings of solid dispersions. Spatial separation by either coating or the use of micro-containers...... before single molecules are available for the formation of crystal nuclei, thus stabilizing the amorphous form....

  17. Mechanism for enhanced absorption of a solid dispersion formulation of LY2300559 using the artificial stomach duodenum model.

    Science.gov (United States)

    Polster, Christopher S; Wu, Sy-Juen; Gueorguieva, Ivelina; Sperry, David C

    2015-04-06

    An artificial stomach duodenum (ASD) model has been used to demonstrate the performance difference between two formulations of LY2300559, a low-solubility acidic developmental drug. The two formulations investigated were a conventional high-shear wet granulation (HSWG) formulation and a solid dispersion formulation. A pharmacokinetic study in humans demonstrated the enhanced performance of the solid dispersion formulation relative to the HSWG formulation. The Cmax and AUC of the solid dispersion was 2.6 and 1.9 times greater, respectively, compared to the HSWG formulation. In the ASD, the solid dispersion formulation performance was characterized by three main phases: (1) rapid release in the stomach, creating a supersaturated concentration of drug, (2) precipitation in the stomach, and (3) rapid redissolution of the precipitate in the duodenum to concentration levels that are supersaturated relative to crystalline drug. A series of complementary experiments were employed to describe this performance behavior mechanistically. Imaging experiments with a pH indicating dye showed that local pH gradients from meglumine in the solid dispersion formulation were responsible for creating a high initial supersaturation concentration in the stomach. Upon dissipation of meglumine, the drug precipitated in the stomach as an amorphous solid. Because the precipitated drug is in an amorphous form, it can then rapidly redissolve as it transits to the more neutral environment of the duodenum. This unexpected sequence of physical state changes gives a mechanistic explanation for the enhanced in vivo performance of the solid dispersion formulation relative to the HSWG formulation.

  18. Solid state characterization of commercial crystalline and amorphous atorvastatin calcium samples.

    Science.gov (United States)

    Shete, Ganesh; Puri, Vibha; Kumar, Lokesh; Bansal, Arvind K

    2010-06-01

    Atorvastatin calcium (ATC), an anti-lipid BCS class II drug, is marketed in crystalline and amorphous solid forms. The objective of this study was to perform solid state characterization of commercial crystalline and amorphous ATC drug samples available in the Indian market. Six samples each of crystalline and amorphous ATC were characterized using X-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis, Karl Fisher titrimetry, microscopy (hot stage microscopy, scanning electron microscopy), contact angle, and intrinsic dissolution rate (IDR). All crystalline ATC samples were found to be stable form I, however one sample possessed polymorphic impurity, evidenced in XRPD and DSC analysis. Amongst the amorphous ATC samples, XRPD demonstrated five samples to be amorphous 'form 27', while, one matched amorphous 'form 23'. Thermal behavior of amorphous ATC samples was compared to amorphous ATC generated by melt quenching in DSC. ATC was found to be an excellent glass former with T(g)/T(m) of 0.95. Residual crystallinity was detected in two of the amorphous samples by complementary use of conventional and modulated DSC techniques. The wettability and IDR of all amorphous samples was found to be higher than the crystalline samples. In conclusion, commercial ATC samples exhibited diverse solid state behavior that can impact the performance and stability of the dosage forms.

  19. In-Vitro Characterization and Oral Bioavailability of Organic Solvent-free Solid Dispersions Containing Telmisartan

    DEFF Research Database (Denmark)

    Cao, Yue; Shi, Li-Li; Cao, Qing-Ri

    2016-01-01

    Poorly water-soluble drugs often suffer from limited or irreproducible clinical response due to their low solubility and dissolution rate. In this study, organic solvent-free solid dispersions (OSF-SDs) containing telmisartan (TEL) were prepared using polyvinylpyrrolidone K30 (PVP K30....... The results from DSC, XRD showed that TEL was molecularly dispersed in the OSF-SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between TEL and its carriers. The OSF-SDs exhibited significantly higher AUC0-24 h and Cmax, but similar Tmax as compared...

  20. Surface Solid Dispersion and Solid Dispersion of Meloxicam: Comparison and Product Development.

    Science.gov (United States)

    Chaturvedi, Mayank; Kumar, Manish; Pathak, Kamla; Bhatt, Shailendra; Saini, Vipin

    2017-12-01

    Purpose: A comparative study was carried out between surface solid dispersion (SSD) and solid dispersion (SD) of meloxicam (MLX) to assess the solubility and dissolution enhancement approach and thereafter develop as patient friendly orodispersible tablet. Methods: Crospovidone (CPV), a hydrophilic carrier was selected for SSD preparation on the basis of 89% in- vitro MLX adsorption, 19% hydration capacity and high swelling index. SD on the other hand was made with PEG4000. Both were prepared by co-grinding and solvent evaporation method using drug: carrier ratios of 1:1, 1:4, and 1:8. Formulation SSDS3 (MLX: CPV in 1:8 ratio) made by solvent evaporation method showed t 50% of 28 min and 80.9% DE 50min which was higher in comparison to the corresponding solid dispersion, SDS3 (t 50% of 35min and 76.4% DE 50min ). Both SSDS3 and SDS3 were developed as orodispersible tablets and evaluated. Results: Tablet formulation F3 made with SSD3 with a disintegration time of 11 secs, by wetting time= 6 sec, high water absorption of 78%by wt and cumulative drug release of 97% proved to be superior than the tablet made with SD3. Conclusion: Conclusively, the SSD of meloxicam has the potential to be developed as fast acing formulation that can ensure almost complete release of drug.

  1. Surface Solid Dispersion and Solid Dispersion of Meloxicam: Comparison and Product Development

    Directory of Open Access Journals (Sweden)

    Mayank Chaturvedi

    2017-12-01

    Full Text Available Purpose: A comparative study was carried out between surface solid dispersion (SSD and solid dispersion (SD of meloxicam (MLX to assess the solubility and dissolution enhancement approach and thereafter develop as patient friendly orodispersible tablet. Methods: Crospovidone (CPV, a hydrophilic carrier was selected for SSD preparation on the basis of 89% in- vitro MLX adsorption, 19% hydration capacity and high swelling index. SD on the other hand was made with PEG4000. Both were prepared by co-grinding and solvent evaporation method using drug: carrier ratios of 1:1, 1:4, and 1:8. Formulation SSDS3 (MLX: CPV in 1:8 ratio made by solvent evaporation method showed t50% of 28 min and 80.9% DE50min which was higher in comparison to the corresponding solid dispersion, SDS3 (t50% of 35min and 76.4% DE50min. Both SSDS3 and SDS3 were developed as orodispersible tablets and evaluated. Results: Tablet formulation F3 made with SSD3 with a disintegration time of 11 secs, by wetting time= 6 sec, high water absorption of 78%by wt and cumulative drug release of 97% proved to be superior than the tablet made with SD3. Conclusion: Conclusively, the SSD of meloxicam has the potential to be developed as fast acing formulation that can ensure almost complete release of drug.

  2. Development of amorphous dispersions of artemether with hydrophilic polymers via spray drying: Physicochemical and in silico studies

    Directory of Open Access Journals (Sweden)

    Jaywant N. Pawar

    2016-06-01

    Full Text Available Artemether (ARM is a poorly water soluble and poorly permeable drug effective against acute and severe falciparum malaria, hence there is a strong need to improve its solubility. The objective of the study was to enhance the solubility and dissolution rate of ARM by preparation of solid dispersions using spray-drying technique. Solid dispersions of ARM were prepared with Soluplus, Kollidon VA 64, HPMC and Eudragit EPO at weight ratios of 1:1, 1:2, 1:3 using spray drying technology, and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC, and X-ray powder diffraction (XRD to identify the physicochemical interaction between drug and carrier, as well as effect on dissolution. The prepared solid dispersion of ARM with polymers showed reduced crystallinity as compared to neat ARM, which was confirmed by DSC and XRD. Drug/polymer interactions were studied in-silico by docking and molecular dynamics which indicated formation of van der Waals type of interactions of ARM with the polymers. Based on solubility studies, the optimum drug/Soluplus ratio was found to be 1:3. The dissolution studies of formulation SD3 showed highest drug release up to 82% compared to neat ARM giving only 20% at 60 minutes. The spray-dried products were free of crystalline ARM; possessed higher dissolution rates, and were stable over a period according to ICH guidelines. These findings suggest that an amorphous solid dispersion of ARM could be a viable option for enhancing the dissolution rate of ARM.

  3. Investigating the effect of moisture protection on solid-state stability and dissolution of fenofibrate and ketoconazole solid dispersions using PXRD, HSDSC and Raman microscopy.

    Science.gov (United States)

    Kanaujia, Parijat; Lau, Grace; Ng, Wai Kiong; Widjaja, Effendi; Schreyer, Martin; Hanefeld, Andrea; Fischbach, Matthias; Saal, Christoph; Maio, Mario; Tan, Reginald B H

    2011-09-01

    Enhanced dissolution of poorly soluble active pharmaceutical ingredients (APIs) in amorphous solid dispersions often diminishes during storage due to moisture-induced re-crystallization. This study aims to investigate the influence of moisture protection on solid-state stability and dissolution profiles of melt-extruded fenofibrate (FF) and ketoconazole (KC) solid dispersions. Samples were kept in open, closed and Activ-vials(®) to control the moisture uptake under accelerated conditions. During 13-week storage, changes in API crystallinity were quantified using powder X-ray diffraction (PXRD) (Rietveld analysis) and high sensitivity differential scanning calorimetry (HSDSC) and compared with any change in dissolution profiles. Trace crystallinity was observed by Raman microscopy, which otherwise was undetected by PXRD and HSDSC. Results showed that while moisture protection was ineffective in preventing the re-crystallization of amorphous FF, KC remained X-ray amorphous despite 5% moisture uptake. Regardless of the degree of crystallinity increase in FF, the enhanced dissolution properties were similarly diminished. Moisture uptake above 10% in KC samples also led to re-crystallization and significant decrease in dissolution rates. In conclusion, eliminating moisture sorption may not be sufficient in ensuring the stability of solid dispersions. Analytical quantification of API crystallinity is crucial in detecting subtle increase in crystallinity that can diminish the enhanced dissolution properties of solid dispersions.

  4. Investigation of Solid Dispersion of Atorvastatin Calcium in ...

    African Journals Online (AJOL)

    ATC), a poorly watersoluble 3-hydroxy 3-methyl glutaryl CoA (HMG-CoA) reductase inhibitor, by a solid dispersion technique using polyethylene glycol 6000 (PEG 6000) or polyvinylpyrrolidone k30 (PVP K30). Methods: The solid dispersions were ...

  5. Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions.

    Science.gov (United States)

    Liu, Yanyan; Wang, Tianzi; Ding, Wenya; Dong, Chunliu; Wang, Xiaoting; Chen, Jianqing; Li, Yanhua

    2018-06-01

    The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher C max values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

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

    Science.gov (United States)

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

    2015-10-15

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

  7. Enhancement of dissolution of Telmisartan through use of solid dispersion technique surface solid dispersion

    Directory of Open Access Journals (Sweden)

    Bhumika Patel

    2012-01-01

    Full Text Available The present study was aimed to increase the solubility of the poorly water soluble drug Telmisartan by using Surface solid dispersion (SSD made of polymers like Poloxamer 407, PEG 6000 by Solvent evaporation method. The drug was solubilized by surfactants and/or polymers then adsorbed onto the surface of extremely fine carriers to increase its surface area and to form the SSD which give the more Surface area for absorption of the drug. A 2 2 full factorial design was used to investigate for each carrier the joint influence of formulation variables: Amount of carrier and adsorbent. Saturation solubility studies shows the improvement in solubility of drug batch SSD 8 give more solubility improvement than the other batch, in-vitro dissolution of pure drug, physical mixtures and SSDs were carried out in that SSDs were found to be effective in increasing the dissolution rate of Telmisartan in form of SSD when compared to pure drug. Also FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and Surface solid dispersion. Furthermore, both DSC and X-ray diffraction showed a decrease in the melting enthalpy and reduced drug crystallinity consequently in SSDs. However, infrared spectroscopy revealed no drug interactions with the carriers.

  8. Solid dispersions of Myricetin with enhanced solubility: Formulation, characterization and crystal structure of stability-impeding Myricetin monohydrate crystals

    Science.gov (United States)

    Mureşan-Pop, M.; Pop, M. M.; Borodi, G.; Todea, M.; Nagy-Simon, T.; Simon, S.

    2017-08-01

    Three solid dispersion forms of Myricetin combined with the Polyvinylpyrrolidone were successfully prepared by spray drying method, and characterized by X-ray powder diffraction, thermal analysis, infrared spectroscopy and optical microscopy. Zeta potential measurements provided indications on solid dispersions stability in aqueous suspension related to their storage at elevated temperature and relative humidity, which depends on the Myricetin load. By increase of Myricetin load, the stability of the solid dispersion is impeded due to growth of Myricetin monohydrate crystals. The amorphous dispersions with 10% and 50% Myricetin load are stable and, compared to pure Myricetin, their aqueous solubility is enhanced by a factor of 47 and 13, respectively. The dispersion with 80% Myricetin load is unstable on storage, and this behavior acts in conjunction with the development of Myricetin monohydrate crystals. Single-crystal X-ray diffraction results obtained for Myricetin monohydrate reveal a structure of an infinite 2D network of hydrogen-bonded molecules involving all six hydroxyl groups of Myricetin. The water molecules are positioned in between the infinite chains, and contribute via H-bonds to robust crystal packing. The calculated needle-like morphology of monohydrate form is in agreement with the optical microscopy results. The study shows that the solid amorphous dispersions with up to 50% Myricetin load are a viable option for achieving substantial solubility improvement of Myricetin, and supports their potential use in pharmaceutical applications.

  9. Dissolution rate enhancement of repaglinide by solid dispersion

    African Journals Online (AJOL)

    Keywords: Diabetes, Solid dispersion, Repaglinide, Solubility, Dissolution, Burst release. Tropical Journal of ... high lipophilicity (logP = 3.97) and relatively low oral bioavailability (56 .... II drug, i.e., low soluble and high permeable in nature. As.

  10. Derivation of Hamaker Dispersion Energy of Amorphous Carbon Surfaces in Contact with Liquids Using Photoelectron Energy-Loss Spectra

    Science.gov (United States)

    Godet, Christian; David, Denis

    2017-12-01

    Hamaker interaction energies and cutoff distances have been calculated for disordered carbon films, in contact with purely dispersive (diiodomethane) or polar (water) liquids, using their experimental dielectric functions ɛ ( q, ω) obtained over a broad energy range. In contrast with previous works, a q-averaged q is derived from photoelectron energy-loss spectroscopy (XPS-PEELS) where the energy loss function (ELF) q is a weighted average over allowed transferred wave vector values, q, given by the physics of bulk plasmon excitation. For microcrystalline diamond and amorphous carbon films with a wide range of (sp3/sp2 + sp3) hybridization, non-retarded Hamaker energies, A 132 ( L < 1 nm), were calculated in several configurations, and distance and wavenumber cutoff values were then calculated based on A 132 and the dispersive work of adhesion obtained from contact angles. A geometric average approximation, H 0 CVL = ( H 0 CVC H 0 LVL )1/2, holds for the cutoff separation distances obtained for carbon-vacuum-liquid (CVL), carbon-vacuum-carbon (CVC) and liquid-vacuum-liquid (LVL) equilibrium configurations. The linear dependence found for A CVL, A CLC and A CLV values as a function of A CVC, for each liquid, allows predictive relationships for Hamaker energies (in any configuration) using experimental determination of the dispersive component of the surface tension, {γ}_{CV}^d , and a guess value of the cutoff distance H 0 CVC of the solid. [Figure not available: see fulltext.

  11. A REVIEW ON SOLID DISPERSION: A DISSOLUTION ENHANCEMENT TECHNIQUE

    OpenAIRE

    Ingle U.S.; Gaikwad P.D.; Bankar V.H.; Pawar S.P.

    2011-01-01

    The enhancement of the oral bioavailability is currently one of the greatest challenges in the development of poorly water soluble drugs. To increase the dissolution and hence the bioavaibility it is important to increase the solubility of the poorly water soluble drugs. One of the possible ways to overcome this limitation is the use of solid dispersion technology. This article contains the different methods and mechanism used in the solid dispersion technology also overlooks the various carr...

  12. Enhanced bioavailability of sirolimus via preparation of solid dispersion nanoparticles using a supercritical antisolvent process

    Directory of Open Access Journals (Sweden)

    Kim MS

    2011-11-01

    Full Text Available Min-Soo Kim1, Jeong-Soo Kim1, Hee Jun Park1, Won Kyung Cho1,3, Kwang-Ho Cha1,3, Sung-Joo Hwang2,31College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea, 2College of Pharmacy, 3Yonsei Institute of Pharmaceutical Sciences, Yonsei University, Incheon, Republic of KoreaBackground: The aim of this study was to improve the physicochemical properties and bioavailability of poorly water-soluble sirolimus via preparation of a solid dispersion of nanoparticles using a supercritical antisolvent (SAS process.Methods: First, excipients for enhancing the stability and solubility of sirolimus were screened. Second, using the SAS process, solid dispersions of sirolimus-polyvinylpyrrolidone (PVP K30 nanoparticles were prepared with or without surfactants such as sodium lauryl sulfate (SLS, tocopheryl propylene glycol succinate, Sucroester 15, Gelucire 50/13, and Myrj 52. A mean particle size of approximately 250 nm was obtained for PVP K30-sirolimus nanoparticles. Solid state characterization, kinetic solubility, powder dissolution, stability, and pharmacokinetics were analyzed in rats.Results: X-ray diffraction, differential scanning calorimetry, and high-pressure liquid chromatography indicated that sirolimus existed in an anhydrous amorphous form within a solid dispersion of nanoparticles and that no degradation occurred after SAS processing. The improved supersaturation and dissolution of sirolimus as a solid dispersion of nanoparticles appeared to be well correlated with enhanced bioavailability of oral sirolimus in rats. With oral administration of a solid dispersion of PVP K30-SLS-sirolimus nanoparticles, the peak concentration and AUC0→12h of sirolimus were increased by approximately 18.3-fold and 15.2-fold, respectively.Conclusion: The results of this study suggest that preparation of PVP K30-sirolimus-surfactant nanoparticles using the SAS process may be a promising approach for improving the bioavailability of sirolimus

  13. Solid solution and amorphous phase in Ti–Nb–Ta–Mn systems synthesized by mechanical alloying

    Energy Technology Data Exchange (ETDEWEB)

    Aguilar, C., E-mail: claudio.aguilar@usm.cl [Departamento de Ingeniería Metalúrgica y Materiales, Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso (Chile); Guzman, P. [Departamento de Ingeniería Metalúrgica y Materiales, Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso (Chile); Lascano, S. [Departamento de Ingeniería Mecánica, Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso (Chile); Parra, C. [Departamento de Física, Universidad Técnica Federico Santa María, Av. España 1680, Valparaíso (Chile); Bejar, L. [Instituto de Investigaciones Metalúrgicas, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, Morelia C.P. 58000, Michoacán (Mexico); Medina, A. [Facultad de Ingeniería Mecánica, Universidad Michoacana de San Nicolás de Hidalgo, Ciudad Universitaria, C.P. 58000, Michoacán (Mexico); Guzman, D. [Departamento de Metalurgia, Universidad de Atacama, Av. España 485, Copiapó (Chile)

    2016-06-15

    This work discusses the formation of Ti–30Nb–13Ta–xMn (x: 2, 4 and 6 wt%) solid solution by mechanical alloying using a shaker mill. A solid solution was formed after 15 h of milling and an amorphous phase was formed after 30 h of milling, according to X-ray diffraction results. Disappearance of strongest X-ray diffraction peaks of Nb, Ta and Mn indicated the formation of solid solution, while, X-ray diffraction patterns of powders milled for 30 h showed an amorphous hump with crystalline peaks in the angular range of 35–45° in 2θ. TEM image analysis showed the presence of nanocrystalline intermetallic compounds embedded in an amorphous matrix. Mn{sub 2}Ti, MnTi and NbTi{sub 4} intermetallic compounds were detected and revealed crystallites with size ranging from 3 to 20 nm. The Gibbs free energy for the formation of solid solution and amorphous phase of three ternary systems (Ti–Nb–Ta, Ti–Nb–Mn and Ti–Ta–Mn) was calculated using extended Miedema's model. Experimental and thermodynamic data confirmed that solid solution was first formed in the alloy with 6wt% Mn followed by the formation of an amorphous phase as milling time increases. The presence of Mn promoted the formation of amorphous phase because the atomic radius difference between Mn with Ti, Nb and Ta. - Highlights: • Thermodynamics analysis of extension of solid solution of the Ti–Nb–Ta–Mn system. • Formation of amorphous phase and intermetallic compounds were observed. • Nanocrystalline intermetallic compounds were formed with the sizes between 3 and 20 nm.

  14. Enhancement of carvedilol solubility by solid dispersion technique using cyclodextrins, water soluble polymers and hydroxyl acid.

    Science.gov (United States)

    Yuvaraja, K; Khanam, Jasmina

    2014-08-05

    Aim of the present work is to enhance aqueous solubility of carvedilol (CV) by solid dispersion technique using wide variety of carriers such as: β-cyclodextrin (βCD), hydroxypropyl-β-cyclodextrin (HPβCD), tartaric acid (TA), polyvinyl pyrrolidone K-30 (PVP K-30) and poloxamer-407 (PLX-407). Various products of 'CV-solid dispersion' had been studied extensively in various pH conditions to check enhancement of solubility and dissolution characteristics of carvedilol. Any physical change upon interaction between CV and carriers was confirmed by instrumental analysis: XRD, DSC, FTIR and SEM. Negative change of Gibb's free energy and complexation constants (Kc, 75-240M(-1), for cyclodextrins and 1111-20,365M(-1), for PVP K-30 and PLX-407) were the evidence of stable nature of the binding between CV and carriers. 'Solubility enhancement factor' of ionized-CV was found high enough (340 times) with HPβCD in presence of TA. TA increases the binding efficiency of cyclodextrin and changing the pH of microenvironment in dissolution medium. In addition, ionization process was used to increase the apparent intrinsic solubility of drug. In vitro, dissolution time of CV was remarkably reduced in the solid dispersion system compared to that of pure drug. This may be attributed to increased wettability, dispersing ability and transformation of crystalline state of drug to amorphous one. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Stabilizing ability of surfactant on physicochemical properties of drug nanoparticles generated from solid dispersions.

    Science.gov (United States)

    Thongnopkoon, Thanu; Puttipipatkhachorn, Satit

    2017-07-01

    This study was aimed to examine the nanoparticle formation from redispersion of binary and ternary solid dispersions. Binary systems are composed of various ratios of glibenclamide (GBM) and polyvinylpyrrolidone K30 (PVP-K30), whereas a constant amount at 2.5%w/w of a surfactant, sodium lauryl sulfate (SLS) or Gelucire44/14 (GLC), was added to create ternary systems. GBM nanoparticles were collected after the systems were dispersed in water for 15 min. The obtained nanoparticles were characterized for size distribution, crystallinity, thermal behavior, molecular structure, and dissolution properties. The results indicated that GBM nanoparticles could be formed when the drug content of the systems was lower than 30%w/w in binary systems and ternary systems containing SLS. The particle size ranged from 200 to 500 nm in diameter with narrow size distribution. The particle size was increased with increasing drug content in the systems. The obtained nanoparticles were spherical and showed the amorphous state. Furthermore, because of being amorphous form and reduced particle size, the dissolution of the generated nanoparticles was markedly improved compared with the GBM powder. In contrast, all the ternary solid dispersions prepared with GLC anomalously provided the crystalline particles with the size ranging over 5 µm and irregular shape. Interestingly, this was irrelevant to the drug content in the systems. These results indicated the ability of GLC to destabilize the polymer network surrounding the particles during particle precipitation. Therefore, this study suggested that drug content, quantity, and type of surfactant incorporated in solid dispersions drastically affected the physicochemical properties of the precipitated particles.

  16. Formulation, Characterization, and in Vivo Evaluation of Celecoxib-PVP Solid Dispersion Nanoparticles Using Supercritical Antisolvent Process

    Directory of Open Access Journals (Sweden)

    Eun-Sol Ha

    2014-12-01

    Full Text Available The aim of this study was to develop celecoxib-polyvinylpyrrolidone (PVP solid dispersion nanoparticles with and without surfactant using the supercritical antisolvent (SAS process. The effect of different surfactants such as gelucire 44/14, poloxamer 188, poloxamer 407, Ryoto sugar ester L1695, and d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS on nanoparticle formation and dissolution as well as oral absorption of celecoxib-PVP K30 solid dispersion nanoparticles was investigated. Spherical celecoxib solid dispersion nanoparticles less than 300 nm in size were successfully developed using the SAS process. Analysis by differential scanning calorimetry and powder X-ray diffraction showed that celecoxib existed in the amorphous form within the solid dispersion nanoparticles fabricated using the SAS process. The celecoxib-PVP-TPGS solid dispersion nanoparticles significantly enhanced in vitro dissolution and oral absorption of celecoxib relative to that of the unprocessed form. The area under the concentration-time curve (AUC0→24 h and peak plasma concentration (Cmax increased 4.6 and 5.7 times, respectively, with the celecoxib-PVP-TPGS formulation. In addition, in vitro dissolution efficiency was well correlated with in vivo pharmacokinetic parameters. The present study demonstrated that formulation of celecoxib-PVP-TPGS solid dispersion nanoparticles using the SAS process is a highly effective strategy for enhancing the bioavailability of poorly water-soluble celecoxib.

  17. Relating hydrogen-bonding interactions with the phase behavior of naproxen/PVP K 25 solid dispersions: evaluation of solution-cast and quench-cooled films.

    Science.gov (United States)

    Paudel, Amrit; Nies, Erik; Van den Mooter, Guy

    2012-11-05

    In this work, we investigated the relationship between various intermolecular hydrogen-bonding (H-bonding) interactions and the miscibility of the model hydrophobic drug naproxen with the hydrophilic polymer polyvinylpyrrolidone (PVP) across an entire composition range of solid dispersions prepared by quasi-equilibrium film casting and nonequilibrium melt quench cooling. The binary phase behavior in solid dispersions exhibited substantial processing method dependence. The solid state solubility of crystalline naproxen in PVP to form amorphous solid dispersions was 35% and 70% w/w naproxen in solution-cast films and quench-cooled films, respectively. However, the presence of a single mixed phase glass transition indicated the amorphous miscibility to be 20% w/w naproxen for the films, beyond which amorphous-amorphous and/or crystalline phase separations were apparent. This was further supported by the solution state interactions data such as PVP globular size distribution and solution infrared spectral profiles. The borderline melt composition showed cooling rate dependence of amorphization. The glass transition and melting point depression profiles of the system were treated with the analytical expressions based on Flory-Huggins mixing theory to interpolate the equilibrium solid solubility. FTIR analysis and subsequent spectral deconvolution revealed composition and miscibility dependent variations in the strength of drug-polymer intermolecular H-bonding. Two types of H-bonded populations were evidenced from 25% w/w and 35% w/w naproxen in solution-cast films and quench-cooled films, respectively, with the higher fraction of strongly H-bonded population in the drug rich domains of phase separated amorphous film compositions and highly drug loaded amorphous quench-cooled dispersions.

  18. Development of novel sibutramine base-loaded solid dispersion with gelatin and HPMC: physicochemical characterization and pharmacokinetics in beagle dogs.

    Science.gov (United States)

    Lim, Hyun-Tae; Balakrishnan, Prabagar; Oh, Dong Hoon; Joe, Kwan Hyung; Kim, Young Ran; Hwang, Doo Hyung; Lee, Yong-Bok; Yong, Chul Soon; Choi, Han-Gon

    2010-09-15

    To develop a novel sibutramine base-loaded solid dispersion with enhanced solubility and bioavailability, various solid dispersions were prepared using a spray drying technique with hydrophilic polymers such as gelatin, HPMC and citric acid. Their solubility, thermal characteristics and crystallinity were investigated. The dissolution and pharmacokinetics of the sibutramine base-loaded solid dispersion were then compared with a sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The solid dispersions prepared with gelatin gave higher drug solubility than those prepared without gelatin, irrespective of the amount of polymer. The sibutramine base-loaded solid dispersions containing hydrophilic polymer and citric acid showed higher drug solubility compared to sibutramine base and sibutramine hydrochloride monohydrate. Among the formulations tested, the solid dispersion composed of sibutramine base/gelatin/HPMC/citric acid at the weight ratio of 1/0.8/0.2/0.5 gave the highest solubility of 5.03+/-0.24 mg/ml. Our DSC and powder X-ray diffraction results showed that the drug was present in an altered amorphous form in this solid dispersion. The difference factor (f(1)) values between solid dispersion and commercial product were 2.82, 6.65 and 6.31 at pH 1.2, 4.0 and 6.8, respectively. Furthermore, they had the similarity factor (f(2)) value of 65.68, 53.43 and 58.97 at pH 1.2, 4.0 and 6.8, respectively. Our results suggested that the solid dispersion and commercial product produced a similar correlation of dissolution profiles at all pH ranges. The AUC, C(max) and T(max) of the parent drug and metabolite I and II from the solid dispersion were not significantly different from those of the commercial product, suggesting that the solid dispersion might be bioequivalent to the commercial product in beagle dogs. Thus, the sibutramine base-loaded solid dispersion prepared with gelatin, HPMC and citric acid is a promising candidate for improving the

  19. Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin

    Directory of Open Access Journals (Sweden)

    Andreas Beyer

    2015-10-01

    Full Text Available To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization behavior of co-amorphous systems are however limited to qualitative evaluations based on the corresponding X-ray powder diffractograms. Therefore, the objective of the study was to develop a quantification model based on X-ray powder diffractometry (XRPD, followed by a multivariate partial least squares regression approach that enables the simultaneous determination of up to four solid state fractions: crystalline naproxen, γ-indomethacin, α-indomethacin as well as co-amorphous naproxen-indomethacin. For this purpose, a calibration set that covers the whole range of possible combinations of the four components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even four solid state phases, involving one co-amorphous phase, can be quantified with this XRPD data-based approach.

  20. Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques.

    Science.gov (United States)

    van Drooge, D J; Hinrichs, W L J; Visser, M R; Frijlink, H W

    2006-03-09

    The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass transition temperature (T(g)), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-diazepam solid dispersions prepared by fusion for all drug loads tested (10-80 wt.%). The T(g) of these solid dispersions gradually changed with composition and decreased from 177 degrees C for pure PVP to 46 degrees C for diazepam. These observations indicate that diazepam was dispersed in PVP on a molecular level. However, in PVP-diazepam solid dispersions prepared by freeze drying, two T(g)'s were observed for drug loads above 35 wt.% indicating phase separation. One T(g) indicated the presence of amorphous diazepam clusters, the other T(g) was attributed to a PVP-rich phase in which diazepam was dispersed on a molecular level. With both the value of the latter T(g) and the DeltaC(p) of the diazepam glass transition the concentrations of molecular dispersed diazepam could be calculated (27-35 wt.%). Both methods gave similar results. Water vapour sorption (DVS) experiments revealed that the PVP-matrix was hydrophobised by the incorporated diazepam. TMDSC and DVS results were used to estimate the size of diazepam clusters in freeze dried PVP-diazepam solid dispersions, which appeared to be in the nano-meter range. The inulin-diazepam solid dispersions prepared by spray freeze drying showed one T(g) for drug loads up to 35 wt.% indicating homogeneous distribution on a molecular level. However, this T(g) was independent of the drug load, which is unexpected because diazepam has a lower T(g) than inulin (46 and 155 degrees C, respectively). For higher drug loads, a T(g) of diazepam as well as a T(g) of the inulin-rich phase was observed, indicating the formation of amorphous diazepam clusters. From the DeltaC(p) of the diazepam glass transition the amount of molecularly dispersed

  1. Disintegration mediated controlled release supersaturating solid dispersion formulation of an insoluble drug: design, development, optimization, and in vitro evaluation.

    Science.gov (United States)

    Verma, Sanjay; Rudraraju, Varma S

    2015-02-01

    The objective of this study was to develop a solid dispersion based controlled release system for drug substances that are poorly soluble in water. A wax-based disintegration mediated controlled release system was designed based on the fact that an amorphous drug can crystallize out from hydrophilic matrices. For this study, cilostazol (CIL) was selected as the model drug, as it exhibits poor aqueous solubility. An amorphous solid dispersion was prepared to assist the drug to attain a supersaturated state. Povidone was used as carrier for solid dispersion (spray drying technique), hydrogenated vegetable oil (HVO) as wax matrix former, and sodium carboxymethyl cellulose (NaCMC) as a disintegrant. The extreme vertices mixture design (EVMD) was applied to optimize the designed and developed composition. The optimized formulation provided a dissolution pattern which was equivalent to the predicted curve, ascertaining that the optimal formulation could be accomplished with EVMD. The release profile of CIL was described by the Higuchi's model better than zero-order, first-order, and Hixson-Crowell's model, which indicated that the supersaturation state of CIL dominated to allow drug release by diffusion rather than disintegration regulated release as is generally observed by Hixson-Crowell's model. The optimized composition was evaluated for disintegration, dissolution, XRD, and stability studies. It was found that the amorphous state as well as the dissolution profile of CIL was maintained under the accelerated conditions of 40°C/75% RH for 6 months.

  2. Preparation and characterization of celecoxib solid dispersions; comparison of poloxamer-188 and PVP-K30 as carriers

    Directory of Open Access Journals (Sweden)

    Alireza Homayouni

    2014-05-01

    Full Text Available Objective(s:Solid dispersion formulation is the most promising strategy to improve oral bioavailability of poorly water soluble drugs. The aim of this study was to compare the effect of polyvinylpyrrolidone K30 (PVP and poloxamer-188 (PLX as carrier in solid dispersion formulations of celecoxib (CLX. Materials and Methods: Solid dispersions of CLX:PVP or CLX:PLX were prepared at different ratios (2:1, 1:1, 1:2, 1:4, 1:6 by solvent evaporation and melting methods, respectively. The characterization of samples was performed using differential scanning calorimetery (DSC, X-Ray powder diffraction (XRPD and Fourier transform infrared spectroscopy (FT-IR. The Gordon-Taylor equation was used to estimate the Tg of solid dispersion systems and the possibility of the interaction between CLX and PVP. Also, the dissolution rate of all samples was determined. Results: DSC and XRPD analyses confirmed the presence of amorphous state of drug in solid dispersion systems. FT-IR studies showed CLX could participate in hydrogen bonding with PVP whilst no specific interaction between CLX and PLX was observed. Both PVP and PLX enhanced the dissolution rate of drug in solid dispersion samples. The dissolution rate was dependent on the ratio of drug: carrier. Interestingly, the solid dispersion samples of PLX at 2:1 and 1:1 drug: carrier showed slower dissolution rate than pure CLX, whilst these results were not observed for PVP. Conclusion: The effect of PVP on dissolution rate enhancement was more pronounced compared to the other carrier. Having a higher Tg and more effect on dissolution rate, PVP could be considered as a more suitable carrier compared to PLX in solid dispersion formulation of CLX.

  3. Phase transitions of amorphous solid acetone in confined geometry investigated by reflection absorption infrared spectroscopy.

    Science.gov (United States)

    Shin, Sunghwan; Kang, Hani; Kim, Jun Soo; Kang, Heon

    2014-11-26

    We investigated the phase transformations of amorphous solid acetone under confined geometry by preparing acetone films trapped in amorphous solid water (ASW) or CCl4. Reflection absorption infrared spectroscopy (RAIRS) and temperature-programmed desorption (TPD) were used to monitor the phase changes of the acetone sample with increasing temperature. An acetone film trapped in ASW shows an abrupt change in the RAIRS features of the acetone vibrational bands during heating from 80 to 100 K, which indicates the transformation of amorphous solid acetone to a molecularly aligned crystalline phase. Further heating of the sample to 140 K produces an isotropic solid phase, and eventually a fluid phase near 157 K, at which the acetone sample is probably trapped in a pressurized, superheated condition inside the ASW matrix. Inside a CCl4 matrix, amorphous solid acetone crystallizes into a different, isotropic structure at ca. 90 K. We propose that the molecularly aligned crystalline phase formed in ASW is created by heterogeneous nucleation at the acetone-water interface, with resultant crystal growth, whereas the isotropic crystalline phase in CCl4 is formed by homogeneous crystal growth starting from the bulk region of the acetone sample.

  4. Development and characterization of an atorvastatin solid dispersion formulation using skimmed milk for improved oral bioavailability

    Directory of Open Access Journals (Sweden)

    Ankush Choudhary

    2012-08-01

    Full Text Available Atorvastatin has low aqueous solubility resulting in low oral bioavailability (12% and thus presents a challenge in formulating a suitable dosage form. To improve the aqueous solubility, a solid dispersion formulation of atorvastatin was prepared by lyophilization utilising skimmed milk as a carrier. Six different formulations were prepared with varying ratios of drug and carrier and the corresponding physical mixtures were also prepared. The formation of a solid dispersion formulation was confirmed by differential scanning calorimetry and X-ray diffraction studies. The optimum drug-to-carrier ratio of 1:9 enhanced solubility nearly 33-fold as compared to pure drug. In vitro drug release studies exhibited a cumulative release of 83.69% as compared to 22.7% for the pure drug. Additionally, scanning electron microscopy studies suggested the conversion of crystalline atorvastatin to an amorphous form. In a Triton-induced hyperlipidemia model, a 3-fold increase in the lipid lowering potential was obtained with the reformulated drug as compared to pure drug. These results suggest that solid dispersion of atorvastatin using skimmed milk as carrier is a promising approach for oral delivery of atorvastatin.

  5. Encapsulation of solid dispersion in solid lipid particles for dissolution enhancement of poorly water-soluble drug.

    Science.gov (United States)

    Tran, Khanh Thi My; Vo, Toi Van; Tran, Phuong Ha-Lien; Lee, Beom-Jin; Duan, Wei; Tran, Thao Truong-Dinh

    2017-06-05

    The aim of this research was to engineer solid dispersion lipid particles (SD-SLs) in which a solid dispersion (SD) was encapsulated to form the core of solid lipid particles (SLs), thereby achieving an efficient enhancement in the dissolution of a poorly water-soluble drug. Ultrasonication was introduced into the process to obtain micro/nanoscale SLs. The mechanism of dissolution enhancement was investigated by analysing the crystalline structure, molecular interactions, and particle size of the formulations. The drug release from the SD-SLs was significantly greater than that from the SD or SLs alone. This enhancement in drug release was dependent on the preparation method and the drug-to-polymer ratio of the SD. With an appropriate amount of polymer in the SD, the solidification method had the potential to alter the drug crystallinity to an amorphous state, resulting in particle uniformity and molecular interactions in the SD-SLs. The proposed system provides a new strategy for enhancing the dissolution rate of poorly water-soluble drugs and further improving their bioavailability. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Formation of soft magnetic high entropy amorphous alloys composites containing in situ solid solution phase

    Science.gov (United States)

    Wei, Ran; Sun, Huan; Chen, Chen; Tao, Juan; Li, Fushan

    2018-03-01

    Fe-Co-Ni-Si-B high entropy amorphous alloys composites (HEAACs), which containing high entropy solid solution phase in amorphous matrix, show good soft magnetic properties and bending ductility even in optimal annealed state, were successfully developed by melt spinning method. The crystallization phase of the HEAACs is solid solution phase with body centered cubic (BCC) structure instead of brittle intermetallic phase. In addition, the BCC phase can transformed into face centered cubic (FCC) phase with temperature rise. Accordingly, Fe-Co-Ni-Si-B high entropy alloys (HEAs) with FCC structure and a small amount of BCC phase was prepared by copper mold casting method. The HEAs exhibit high yield strength (about 1200 MPa) and good plastic strain (about 18%). Meanwhile, soft magnetic characteristics of the HEAs are largely reserved from HEAACs. This work provides a new strategy to overcome the annealing induced brittleness of amorphous alloys and design new advanced materials with excellent comprehensive properties.

  7. Mathematical model to analyze the dissolution behavior of metastable crystals or amorphous drug accompanied with a solid-liquid interface reaction.

    Science.gov (United States)

    Hirai, Daiki; Iwao, Yasunori; Kimura, Shin-Ichiro; Noguchi, Shuji; Itai, Shigeru

    2017-04-30

    Metastable crystals and the amorphous state of poorly water-soluble drugs in solid dispersions (SDs), are subject to a solid-liquid interface reaction upon exposure to a solvent. The dissolution behavior during the solid-liquid interface reaction often shows that the concentration of drugs is supersaturated, with a high initial drug concentration compared with the solubility of stable crystals but finally approaching the latter solubility with time. However, a method for measuring the precipitation rate of stable crystals and/or the potential solubility of metastable crystals or amorphous drugs has not been established. In this study, a novel mathematical model that can represent the dissolution behavior of the solid-liquid interface reaction for metastable crystals or amorphous drug was developed and its validity was evaluated. The theory for this model was based on the Noyes-Whitney equation and assumes that the precipitation of stable crystals at the solid-liquid interface occurs through a first-order reaction. Moreover, two models were developed, one assuming that the surface area of the drug remains constant because of the presence of excess drug in the bulk and the other that the surface area changes in time-dependency because of agglomeration of the drug. SDs of Ibuprofen (IB)/polyvinylpyrrolidone (PVP) were prepared and their dissolution behaviors under non-sink conditions were fitted by the models to evaluate improvements in solubility. The model assuming time-dependent surface area showed good agreement with experimental values. Furthermore, by applying the model to the dissolution profile, parameters such as the precipitation rate and the potential solubility of the amorphous drug were successfully calculated. In addition, it was shown that the improvement in solubility with supersaturation was able to be evaluated quantitatively using this model. Therefore, this mathematical model would be a useful tool to quantitatively determine the supersaturation

  8. Crystalline and amorphous solid phases in the classical hard sphere system

    International Nuclear Information System (INIS)

    Aguilera-Navarro, V.C.; Souza, R.F.T.; Llano, M. de; Mini, S.

    1984-01-01

    A qualitative crystalline, as well as amorphous, solid behavior is simultaneously extracted for a classical hard sphere system from its known virial power series expansion in the density augmented by only one further virial coefficient, taken from an extrapolated estimate of the Cauchy-Hadamard radius of convergence criterion. Results are compared with computer simulation data. (Author) [pt

  9. Formation of amorphous Ti-50at.%Pt by solid state reactions during mechanical alloying

    CSIR Research Space (South Africa)

    Mahlatji, ML

    2013-10-01

    Full Text Available Mechanical alloying of an equiatomic mixture of crystalline elemental powders of Ti and Pt in a high-energy ball mill results in formation of an amorphous alloy by solid-state reactions. Mechanical alloying was carried out in an argon atmosphere...

  10. Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniques

    NARCIS (Netherlands)

    van Drooge, D J; Hinrichs, W L J; Visser, M R; Frijlink, H W

    2006-01-01

    The molecular distribution in fully amorphous solid dispersions consisting of poly(vinylpyrrolidone) (PVP)-diazepam and inulin-diazepam was studied. One glass transition temperature (T-g), as determined by temperature modulated differential scanning calorimetry (TMDSC), was observed in PVP-diazepam

  11. Characterisation of Gliclazide-PEG 8000 Solid Dispersions

    African Journals Online (AJOL)

    Erah

    Purpose: The aim of the present study was to characterise gliclazide solid dispersions (SDs) ... Results: The solubility of gliclazide increased with increasing amount of PEG 8000 in aqueous medium. ... FTIR analysis demonstrated the absence of well-defined gliclazide - PEG 8000 .... voltage of 35 kV and 20 mA current. The.

  12. Formulation of Fast-Release Gastroretentive Solid Dispersion of ...

    African Journals Online (AJOL)

    Methods: Hot melt granulation technique was adopted to prepare solid dispersions (SDs) of glibenclamide in .... ml of 0.1M HCl (pH 1.2), stirred at 20 rpm in a water bath (25 ± 0.3 .... cm-1; and SO2 stretching vibration at 1340.43 and 1159.14 ...

  13. Electromagnetic wave absorption properties of composites with micro-sized magnetic particles dispersed in amorphous carbon

    Energy Technology Data Exchange (ETDEWEB)

    Li, Bin Peng [Research Center of Carbon Fiber, Key Laboratory for Liquid–Solid Structural Evolution and Processing of Materials of Ministry of Education, Shandong University, Jinan 250061 (China); Tianjin Binhai New Area Finance Bureau, Tianjin 300450 (China); Wang, Cheng Guo, E-mail: sduwangchg@gmail.com [Research Center of Carbon Fiber, Key Laboratory for Liquid–Solid Structural Evolution and Processing of Materials of Ministry of Education, Shandong University, Jinan 250061 (China); Wang, Wen [Norinco Group China North Material Science and Engineering Technology Group Corporation, Jinan 250031 (China); Yu, Mei Jie; Gao, Rui; Chen, Yang; Xiang Wang, Yan [Research Center of Carbon Fiber, Key Laboratory for Liquid–Solid Structural Evolution and Processing of Materials of Ministry of Education, Shandong University, Jinan 250061 (China)

    2014-09-01

    Composites with micro-sized magnetic particles dispersed in amorphous carbon were fabricated conveniently and economically by carbonizing polyacrylonitrile (PAN) fibers mixed with micro-sized iron particles under different temperatures. The composites were characterized by X-ray diffraction (XRD) and scanning electric microscope (SEM). The electromagnetic (EM) properties were measured by a vector network analyzer in the frequency range of 2–18 GHz based on which analog computations of EM wave absorption properties were carried out. The influences of temperature on phase composition and EM wave absorption properties were also investigated, indicating that the composites had good electromagnetic absorption properties with both electrical loss and magnetic loss. Effective reflection loss (RL<−10 dB) was observed in a large frequency range of 7.5–18 GHz with the absorber thickness of 2.0–3.0 mm for the paraffin samples with composite powders heated up to 750 °C and the minimum absorption peak around −40 dB appeared at approximately 10 GHz with matching thickness of 2.0 mm for the paraffin sample with composite powders heated up to 800 °C. - Highlights: • High-performance electromagnetic wave absorption materials were fabricated conveniently and economically. • The materials are composites with micro-sized magnetic particles dispersed in porous amorphous carbon. • The influences of temperature on phase composition and electromagnetic wave absorption properties were investigated. • The composites heated up to 750 °C and 800 °C had good electromagnetic wave absorption property.

  14. Magnetic properties of Mn-oxide nanoparticles dispersed in an amorphous SiO2 matrix

    Science.gov (United States)

    Milivojević, D.; Babić-Stojić, B.; Jokanović, V.; Jagličić, Z.; Makovec, D.

    2011-03-01

    Samples of Mn-oxide nanoparticles dispersed in an amorphous SiO2 matrix with manganese concentration 0.7 and 3 at% have been synthesized by a sol-gel method. Transmission electron microscopy analysis has shown that the samples contain agglomerates of amorphous silica particles 10-20 nm in size. In silica matrix two types of Mn-rich particles are dispersed, smaller nanoparticles with dimensions between 3 and 10 nm, and larger crystalline areas consisting of aggregates of the smaller nanoparticles. High-temperature magnetic susceptibility study reveals that dominant magnetic phase at higher temperatures is λ-MnO2. At temperatures below TC=43 K strong ferrimagnetism originating from the minor Mn3O4 phase masks the relatively weak magnetism of λ-MnO2 with antiferromagnetic interactions. Magnetic field dependence of the maximum in the zero-field-cooled magnetization for both the samples in the vicinity of 40 K, and a frequency shift of the real component of the ac magnetic susceptibility in the sample with 3 at% Mn suggest that the magnetic moments of the smaller Mn3O4 nanoparticles with dimensions below 10 nm are exposed to thermally activated blocking process just below the Curie temperature TC. Appearance of a maximum in the zero-field-cooled magnetization for both the samples below 10 K indicates possible spin glass freezing of the magnetic moments at low temperatures which might occur in the geometrically frustrated Mn sublattice of the λ-MnO2 crystal structure.

  15. Solubility Enhancement and Formulation of Mouth Dissolving Tablet of Clonazepam with Solid Dispersion Technology

    Directory of Open Access Journals (Sweden)

    Swati C. Jagdale

    2012-01-01

    Full Text Available Clonazepam (CLZ is an anticonvulsant benzodiazepine widely used in the treatment of epilepsy. CLZ is a BCS Class II drug and its bioavailability is thus dissolution limited. The objective of the present study was to prepare solid dispersions (SDs of CLZ by various techniques, using the amphiphilic carrier Gelucire 50/13 in various proportions, to increase its water solubility. Drug-polymer interactions were investigated by Fourier-transform infrared (FTIR and UltraViolet (UV spectroscopy. The SDs were characterized physically by differential scanning calorimetry (DSC and X-ray diffraction (XRD. A phase solubility study was performed and the stability constant (Ks was found to be 275.27, while the negative Gibbs free energy (ΔGo tr indicated spontaneous solubilization of the drug. The dissolution study showed that the SDs considerably enhanced the dissolution rate of the drug. The FTIR and UV spectra revealed no chemical incompatibility between the drug and Gelucire 50/13. XRD patterns and the DSC profiles indicated the CLZ was in the amorphous form, which explains the improved dissolution rate of the drug from its SDs. Finally, mouth dissolving tablets (MDTs were prepared from the optimized batches (kneading method of solid dispersion, using crospovidone and Doshion P544 resin as superdisintegrants. The tablets were characterized by in-vitro disintegration and dissolution tests. The study of the MDTs showed disintegration times in the range 32.0±0.85 to 20.0±1.30 sec and dissolution was faster than for the commercial preparation. In conclusion, this investigation demonstrated the potential of solid dispersions of a drug with Gelucire 50/13 for promoting the dissolution of the drug and contributed to the understanding of the effect of a superdisintegrant on mouth dissolving tablets containing a solid dispersion of a hydrophobic drug.

  16. Materials modeling by design: applications to amorphous solids

    International Nuclear Information System (INIS)

    Biswas, Parthapratim; Tafen, D N; Inam, F; Cai Bin; Drabold, D A

    2009-01-01

    In this paper, we review a host of methods used to model amorphous materials. We particularly describe methods which impose constraints on the models to ensure that the final model meets a priori requirements (on structure, topology, chemical order, etc). In particular, we review work based on quench from the melt simulations, the 'decorate and relax' method, which is shown to be a reliable scheme for forming models of certain binary glasses. A 'building block' approach is also suggested and yields a pleading model for GeSe 1.5 . We also report on the nature of vulcanization in an Se network cross-linked by As, and indicate how introducing H into an a-Si network develops into a-Si:H. We also discuss explicitly constrained methods including reverse Monte Carlo (RMC) and a novel method called 'Experimentally Constrained Molecular Relaxation'. The latter merges the power of ab initio simulation with the ability to impose external information associated with RMC.

  17. Athermal brittle-to-ductile transition in amorphous solids.

    Science.gov (United States)

    Dauchot, Olivier; Karmakar, Smarajit; Procaccia, Itamar; Zylberg, Jacques

    2011-10-01

    Brittle materials exhibit sharp dynamical fractures when meeting Griffith's criterion, whereas ductile materials blunt a sharp crack by plastic responses. Upon continuous pulling, ductile materials exhibit a necking instability that is dominated by a plastic flow. Usually one discusses the brittle to ductile transition as a function of increasing temperature. We introduce an athermal brittle to ductile transition as a function of the cutoff length of the interparticle potential. On the basis of extensive numerical simulations of the response to pulling the material boundaries at a constant speed we offer an explanation of the onset of ductility via the increase in the density of plastic modes as a function of the potential cutoff length. Finally we can resolve an old riddle: In experiments brittle materials can be strained under grip boundary conditions and exhibit a dynamic crack when cut with a sufficiently long initial slot. Mysteriously, in molecular dynamics simulations it appeared that cracks refused to propagate dynamically under grip boundary conditions, and continuous pulling was necessary to achieve fracture. We argue that this mystery is removed when one understands the distinction between brittle and ductile athermal amorphous materials.

  18. Amorphous-crystalline interface evolution during Solid Phase Epitaxy Regrowth of SiGe films amorphized by ion implantation

    International Nuclear Information System (INIS)

    D'Angelo, D.; Piro, A.M.; Mirabella, S.; Bongiorno, C.; Romano, L.; Terrasi, A.; Grimaldi, M.G.

    2007-01-01

    Transmission Electron Microscopy was combined with Time Resolved Reflectivity to study the amorphous-crystalline (a-c) interface evolution during Solid Phase Epitaxy Regrowth (SPER) of Si 0.83 Ge 0.17 films deposited on Si by Molecular Beam Epitaxy and amorphized with Ge + ion implantation. Starting from the Si/SiGe interface, a 20 nm thick layer regrows free of defects with the same SPER rate of pure Si. The remaining SiGe regrows with planar defects and dislocations, accompanied by a decrease of the SPER velocity. The sample was also studied after implantation with B or P. In these cases, the SPER rate raises following the doping concentration profile, but no difference in the defect-free layer thickness was observed compared to the un-implanted sample. On the other hand, B or P introduction reduces the a-c interface roughness, while B-P co-implantation produces roughness comparable to the un-implanted sample

  19. Physiochemical Characterization and Release Rate Studies of SolidDispersions of Ketoconazole with Pluronic F127 and PVP K-30

    Science.gov (United States)

    Kumar, Pankaj; Mohan, Chander; KanamSrinivasan Uma Shankar, Mara; Gulati, Monica

    2011-01-01

    In the present study solid dispersions of the antifungal drug Ketoconazole were prepared with Pluronic F-127 and PVP K-30 with an intention to improve its dissolution properties. Investigations of the properties of the dispersions were performed using release studies, Differential scanning calorimetery (DSC), X-ray powder diffraction (XRD) and Fourier transform infrared (FTIR). The results obtained showed that the rate of dissolution of Ketoconazole was considerably improved when formulated in solid dispersions with PVP K-30 and Pluronic F-127 as compared with pure drug and physical mixtures. The results from DSC and XRD studies showed the transition of crystalline nature of drug to amorphous form, while FTIR studies demonstrated the absence of drug-carriers interaction. PMID:24250403

  20. Amorphization within the tablet

    DEFF Research Database (Denmark)

    Doreth, Maria; Hussein, Murtadha Abdul; Priemel, Petra A.

    2017-01-01

    , the feasibility of microwave irradiation to prepare amorphous solid dispersions (glass solutions) in situ was investigated. Indomethacin (IND) and polyvinylpyrrolidone K12 (PVP) were tableted at a 1:2 (w/w) ratio. In order to study the influence of moisture content and energy input on the degree of amorphization......, tablet formulations were stored at different relative humidity (32, 43 and 54% RH) and subsequently microwaved using nine different power-time combinations up to a maximum energy input of 90 kJ. XRPD results showed that up to 80% (w/w) of IND could be amorphized within the tablet. mDSC measurements...

  1. Local yield stress statistics in model amorphous solids

    Science.gov (United States)

    Barbot, Armand; Lerbinger, Matthias; Hernandez-Garcia, Anier; García-García, Reinaldo; Falk, Michael L.; Vandembroucq, Damien; Patinet, Sylvain

    2018-03-01

    We develop and extend a method presented by Patinet, Vandembroucq, and Falk [Phys. Rev. Lett. 117, 045501 (2016), 10.1103/PhysRevLett.117.045501] to compute the local yield stresses at the atomic scale in model two-dimensional Lennard-Jones glasses produced via differing quench protocols. This technique allows us to sample the plastic rearrangements in a nonperturbative manner for different loading directions on a well-controlled length scale. Plastic activity upon shearing correlates strongly with the locations of low yield stresses in the quenched states. This correlation is higher in more structurally relaxed systems. The distribution of local yield stresses is also shown to strongly depend on the quench protocol: the more relaxed the glass, the higher the local plastic thresholds. Analysis of the magnitude of local plastic relaxations reveals that stress drops follow exponential distributions, justifying the hypothesis of an average characteristic amplitude often conjectured in mesoscopic or continuum models. The amplitude of the local plastic rearrangements increases on average with the yield stress, regardless of the system preparation. The local yield stress varies with the shear orientation tested and strongly correlates with the plastic rearrangement locations when the system is sheared correspondingly. It is thus argued that plastic rearrangements are the consequence of shear transformation zones encoded in the glass structure that possess weak slip planes along different orientations. Finally, we justify the length scale employed in this work and extract the yield threshold statistics as a function of the size of the probing zones. This method makes it possible to derive physically grounded models of plasticity for amorphous materials by directly revealing the relevant details of the shear transformation zones that mediate this process.

  2. Structural Relaxations and Thermodynamic Properties of Molecular Amorphous Solids by Mechanical Milling

    Science.gov (United States)

    Tsukushi, I.; Yamamuro, O.; Matsuo, T.

    The organic crystals of tri-O-methyl-β-cyclodextrin (TMCD) and its three clathrate compounds containing benzoic acid (BA), p-nitrobenzoic acid (NBA) and p-hydroxybenzoic acid (HBA), sucrose (SUC), salicin (SAL), phenolphthalein (PP), 1,3,5-tri-α-naphthylbenzene (TNB) were amorphized by milling with a vibrating mill for 2 ˜ 16 hours at room temperature. The amorphization was checked by differential scanning calorimetry (DSC) and X-ray powder diffraction. The heat capacities of crystals, liquid quenched glasses (LQG), and mechanically-milled amorphous solid (MMAS) of TMCD and TNB were measured with an adiabatic calorimeter in the temperature range between 12 and 375 K. For both compounds, the enthalpy relaxation of MMAS appeared in the wide temperature range below Tg and the released configurational enthalpy was much larger than that of LQG, indicating that MMAS is more disordered and strained than LQG.

  3. Localized solid-state amorphization at grain boundaries in a nanocrystalline Al solid solution subjected to surface mechanical attrition

    Energy Technology Data Exchange (ETDEWEB)

    Wu, X [State Key Laboratory of Nonlinear Mechanics, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100080 (China); Tao, N [Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China); Hong, Y [State Key Laboratory of Nonlinear Mechanics, Institute of Mechanics, Chinese Academy of Sciences, Beijing 100080 (China); Lu, J [LASMIS, University of Technology of Troyes, 10000, Troyes (France); Lu, K [Shenyang National Laboratory for Materials Science, Institute of Metal Research, Chinese Academy of Sciences, Shenyang 110016 (China)

    2005-11-21

    Using high-resolution electron microscopy, localized solid-state amorphization (SSA) was observed in a nanocrystalline (NC) Al solid solution (weight per cent 4.2 Cu, 0.3 Mn, the rest being Al) subjected to a surface mechanical attrition treatment. It was found that the deformation-induced SSA may occur at the grain boundary (GB) where either the high density dislocations or dislocation complexes are present. It is suggested that lattice instability due to elastic distortion within the dislocation core region plays a significant role in the initiation of the localized SSA at defective sites. Meanwhile, the GB of severely deformed NC grains exhibits a continuously varying atomic structure in such a way that while most of the GB is ordered but reveals corrugated configurations, localized amorphization may occur along the same GB.

  4. Characterization of Two Distinct Amorphous Forms of Valsartan by Solid-State NMR.

    Science.gov (United States)

    Skotnicki, Marcin; Apperley, David C; Aguilar, Juan A; Milanowski, Bartłomiej; Pyda, Marek; Hodgkinson, Paul

    2016-01-04

    Valsartan (VAL) is an antihypertensive drug marketed in an amorphous form. Amorphous materials can have different physicochemical properties depending on preparation method, thermal history, etc., but the nature of such materials is difficult to study by diffraction techniques. This study characterizes two different amorphous forms of valsartan (AR and AM) using solid-state NMR (SSNMR) as a primary investigation tool, supported by solution-state NMR, FT-IR, TMDSC, and dissolution tests. The two forms are found to be clearly distinct, with a significantly higher level of structural arrangement in the AR form, as observed in (13)C, (15)N, and (1)H SSNMR. (13)C and (15)N NMR indicates that the fully amorphous material (AM) contains an approximately equal ratio of cis-trans conformers about the amide bond, whereas the AR form exists mainly as one conformer, with minor conformational "defects". (1)H ultrafast MAS NMR shows significant differences in the hydrogen bonding involving the tetrazole and acid hydrogens between the two materials, while (15)N NMR shows that both forms exist as a 1,2,3,4-tetrazole tautomer. NMR relaxation times show subtle differences in local and bulk molecular mobility, which can be connected with the glass transition, the stability of the glassy material, and its response to aging. Counterintuitively the fully amorphous material is found to have a significantly lower dissolution rate than the apparently more ordered AR material.

  5. Solid KHT tumor dispersal for flow cytometric cell kinetic analysis

    International Nuclear Information System (INIS)

    Pallavicini, M.G.; Folstad, L.J.; Dunbar, C.

    1981-01-01

    A bacterial neutral protease was used to disperse KHT solid tumors into single cell suspensions suitable for routine cell kinetic analysis by flow cytometry and for clonogenic cell survival. Neutral protease disaggregation under conditions which would be suitable for routine tumor dispersal was compared with a trypsin/DNase procedure. Cell yield, clonogenic cell survival, DNA distributions of untreated and drug-perturbed tumors, rates of radioactive precursor incorporation during the cell cycle, and preferential cell cycle phase-specific cell loss were investigated. Tumors dispersed with neutral protease yielded approximately four times more cells than those dispersed with trypsin/DNase and approximately a 1.5-fold higher plating efficiency in a semisolid agar system. Quantitative analysis of DNA distributions obtained from untreated and cytosine-arabinoside-perturbed tumors produced similar results with both dispersal procedures. The rates of incorporation of tritiated thymidine during the cell cycle were also similar with neutral protease and trypsin/DNase dispersal. Preferential phase-specific cell loss was not obseved with either technique. We find that neutral protease provides good single cell suspensions of the KHT tumor for cell survival measurements and for cell kinetic analysis of drug-induced perturbations by flow cytometry. In addition, the high cell yields facilitate electronic cell sorting where large numbers of cells are often required

  6. Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process

    Directory of Open Access Journals (Sweden)

    Ha ES

    2015-08-01

    Full Text Available Eun-Sol Ha,1 Jeong-Soo Kim,2 In-hwan Baek,3 Jin-Wook Yoo,1 Yunjin Jung,1 Hyung Ryong Moon,1 Min-Soo Kim1 1College of Pharmacy, Pusan National University, 2Dong-A ST Co Ltd, Yongin, 3College of Pharmacy, Kyungsung University, Busan, South Korea Abstract: In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was <500 nm. Powder X-ray diffraction and differential scanning calorimetry measurements showed that megestrol acetate was present in an amorphous or molecular dispersion state within the solid dispersion nanoparticles. Hydroxypropylmethyl cellulose (HPMC solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by d-a-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0–24 hours and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol

  7. Characterization of gliclazide-polyethylene glycol solid dispersion and its effect on dissolution

    Directory of Open Access Journals (Sweden)

    Moreshwar Pandharinath Patil

    2011-03-01

    Full Text Available The present study was initiated with the objective of studying the in vitro dissolution behavior of gliclazide from its solid dispersion with polyethylene glycol 6000. In this work, a solid dispersion of gliclazide with polyethylene glycol was prepared by the fusion method. In vitro dissolution study of gliclazide, its physical mixture and solid dispersion were carried out to demonstrate the effect of PEG 6000. Analytical techniques of FT-IR spectroscopy, differential scanning calorimetry and X-ray diffractometry were used to characterize the drug in the physical mixtures and solid dispersions. The dissolution studies of solid dispersion and physical mixture showed greater improvement compared to that of the pure drug. The mechanisms for increased dissolution rate may include reduction of crystallite size, a solubilization effect of the carrier, absence of aggregation of drug crystallites, improved wettability and dispersbility of the drug from the dispersion, dissolution of the drug in the hydrophilic carrier or conversion of drug to an amorphous state. The FT-IR spectra suggested that there was no interaction between gliclazide and PEG 6000 when prepared as a solid dispersion. DSC and XRD study indicated that the drug was converted in the amorphous form.O presente trabalho foi realizado com o objetivo de estudar o comportamento in vitro da dissolução da gliclazida a partir da sua dispersão sólida com polietileno glicol 6000. Neste trabalho, as dispersões sólidas de gliclazida com polietileno glicol foram preparadas pelo método de fusão. Os estudo de dissolução in vitro da gliclazida, na mistura física e nas dispersões sólidas foram realizados para demonstrar o efeito de PEG 6000. Técnicas analíticas como espectroscopia FT-IR, calorimetria diferencial de varredura e difração de raios-X foram empregadas para caracterizar o fármaco nas misturas físicas e nas dispersoes sólidas. Os estudos de dissolução demonstraram maior

  8. NATO Advanced Study Institute on Hydrogen in Disordered and Amorphous Solids

    CERN Document Server

    Bowman, Robert

    1986-01-01

    This is the second volume in the NATO ASI series dealing with the topic of hydrogen in solids. The first (V. B76, Metal Hydrides) appeared five years ago and focussed primarily on crystalline phases of hydrided metallic systems. In the intervening period, the amorphous solid state has become an area of intense research activity, encompassing both metallic and non-metallic, e.g. semiconducting, systems. At the same time the problem of storage of hydrogen, which motivated the first ASI, continues to be important. In the case of metallic systems, there were early indications that metallic glasses and disordered alloys may be more corrosion resistant, less susceptible to embrittlement by hydrogen and have a higher hydrogen mobility than ordered metals or intermetallics. All of these properties are desirable for hydrogen storage. Subsequent research has shown that thermodynamic instability is a severe problem in many amorphous metal hydrides. The present ASI has provided an appropriate forum to focus on these issu...

  9. Characterization of degradation products of amorphous and polymorphic forms of clopidogrel bisulphate under solid state stress conditions

    DEFF Research Database (Denmark)

    Raijada, Dhara K; Prasad, Bhagwat; Paudel, Amrit

    2010-01-01

    The present study deals with the stress degradation studies on amorphous and polymorphic forms of clopidogrel bisulphate. The objective was to characterize the degradation products and postulate mechanism of decomposition of the drug under solid state stress conditions. For that, amorphous form, ...

  10. Thermodynamic phase behavior of API/polymer solid dispersions.

    Science.gov (United States)

    Prudic, Anke; Ji, Yuanhui; Sadowski, Gabriele

    2014-07-07

    To improve the bioavailability of poorly soluble active pharmaceutical ingredients (APIs), these materials are often integrated into a polymer matrix that acts as a carrier. The resulting mixture is called a solid dispersion. In this work, the phase behaviors of solid dispersions were investigated as a function of the API as well as of the type and molecular weight of the carrier polymer. Specifically, the solubility of artemisinin and indomethacin was measured in different poly(ethylene glycol)s (PEG 400, PEG 6000, and PEG 35000). The measured solubility data and the solubility of sulfonamides in poly(vinylpyrrolidone) (PVP) K10 and PEG 35000 were modeled using the perturbed-chain statistical associating fluid theory (PC-SAFT). The results show that PC-SAFT predictions are in a good accordance with the experimental data, and PC-SAFT can be used to predict the whole phase diagram of an API/polymer solid dispersion as a function of the kind of API and polymer and of the polymer's molecular weight. This remarkably simplifies the screening process for suitable API/polymer combinations.

  11. Biodiesel fuel production with solid amorphous-zirconia catalysis in fixed bed reactor

    International Nuclear Information System (INIS)

    Furuta, Satoshi; Matsuhashi, Hiromi; Arata, Kazushi

    2006-01-01

    Amorphous zirconia catalysts, titanium-, aluminum-, and potassium-doped zirconias, were prepared and evaluated in the transesterification of soybean oil with methanol at 250 deg. C, and the esterification of n-octanoic acid with methanol at 175-200 deg. C. Titanium- and aluminum-doped zirconias are promising solid catalysts for the production of biodiesel fuels from soybean oil because of their high performance, with over 95% conversion in both of the esterifications

  12. Phenomenology of the plastic flow of amorphous solids induced by heavy-ion bombardment

    International Nuclear Information System (INIS)

    Klaumuenzer, S.; Benyagoub, A.

    1991-01-01

    Amorphous solids exhibit at temperatures far below the glass transition plastic flow when bombarded with fast heavy ions (kinetic energy ∼1 MeV/u). The dimensions perpendicular to the ion beam grow whereas the sample dimension parallel to the ion beam shrinks. The strain tensor describing phenomenologically these dimensional changes is derived from symmetry considerations and compared with experiment. Particular attention is devoted to angular changes, which have not been discussed in this context so far

  13. Movement of correlated atomic particles in amorphous solids

    International Nuclear Information System (INIS)

    Jakas, M.M.

    1983-01-01

    Two problems about energetic ions penetration in solids are studied by using transport theory. The exact solutions of their transport equations are difficult to obtain, making it necesary to resort to variational functionals. The formulation and the approximate solution of the transport equation which is introduced into an adequate variational functional are presented. After recapitulating the generalities of the Rutherford backscattering, its anomalous form is considered. The increase of the number of ions which backscatter from the first atomic layers (approx. 300 A), when the observation angle αsub(o) is very small (αsub(o) less or approx. 0.5 deg), is studied. The difficulty arises from the correlation between the scattering suffered with each atom of the target in the incoming and outcoming paths for those ions which are backscattered at scattering angles close to 180 deg and return to the vacuum through almost the same trajectory traversed in the incoming path. The second problem studied is the transmission of diatomic molecules through thin sheets, where an attempt is made to coherently describe the Coulomb repulsion between the molecular fragments and the multiple scattering. Finally, the results obtained from the calculations are discussed and compared with experimental data. (M.E.L.) [es

  14. Influence of isotopic disorder on solid state amorphization and polyamorphism in solid H2O -D2O solutions

    Science.gov (United States)

    Gromnitskaya, E. L.; Danilov, I. V.; Lyapin, A. G.; Brazhkin, V. V.

    2015-10-01

    We present a low-temperature and high-pressure ultrasonic study of elastic properties of isotopic H2O-D2O solid solutions, comparing their properties with those of the isotopically pure H2O and D2O ices. Measurements were carried out for solid state amorphization (SSA) from 1h to high-density amorphous (HDA) ice upon compression up to 1.8 GPa at 77 K and for the temperature-induced (77 -190 K ) u-HDA (unrelaxed HDA) → e-HDA (expanded HDA) → low-density amorphous (LDA )→1 c cascade of ice transformations near room pressure. There are many similarities in the elasticity behaviour of H2O ,D2O , and H2O-D2O solid solutions, including the softening of the shear elastic modulus as a precursor of SSA and the HDA →LDA transition. We have found significant isotopic effects during H/D substitution, including elastic softening of H2O -D2O solid solutions with respect to the isotopically pure ices in the case of the bulk moduli of ices 1c and 1h and for both bulk and shear elastic moduli of HDA ice at high pressures (>1 GPa ) . This softening is related to the configurational isotopic disorder in the solid solutions. At low pressures, the isotope concentration dependence of the elastic moduli of u-HDA ice changes remarkably and becomes monotonic with pronounced change of the bulk modulus (≈20 %) .

  15. Electron stimulated reactions of methyl iodide coadsorbed with amorphous solid water

    International Nuclear Information System (INIS)

    Perry, C. C.; Faradzhev, N. S.; Madey, T. E.; Fairbrother, D. H.

    2007-01-01

    The electron stimulated reactions of methyl iodide (MeI) adsorbed on and suspended within amorphous solid water (ice) were studied using a combination of postirradiation temperature programmed desorption and reflection absorption infrared spectroscopy. For MeI adsorbed on top of amorphous solid water (ice), electron beam irradiation is responsible for both structural and chemical transformations within the overlayer. Electron stimulated reactions of MeI result principally in the formation of methyl radicals and solvated iodide anions. The cross section for electron stimulated decomposition of MeI is comparable to the gas phase value and is only weakly dependent upon the local environment. For both adsorbed MeI and suspended MeI, reactions of methyl radicals within MeI clusters lead to the formation of ethane, ethyl iodide, and diiodomethane. In contrast, reactions between the products of methyl iodide and water dissociation are responsible for the formation of methanol and carbon dioxide. Methane, formed as a result of reactions between methyl radicals and either parent MeI molecules or hydrogen atoms, is also observed. The product distribution is found to depend on the film's initial chemical composition as well as the electron fluence. Results from this study highlight the similarities in the carbon-containing products formed when monohalomethanes coadsorbed with amorphous solid water are irradiated by either electrons or photons

  16. Thermodynamics of water-solid interactions in crystalline and amorphous pharmaceutical materials.

    Science.gov (United States)

    Sacchetti, Mark

    2014-09-01

    Pharmaceutical materials, crystalline and amorphous, sorb water from the atmosphere, which affects critical factors in the development of drugs, such as the selection of drug substance crystal form, compatibility with excipients, dosage form selection, packaging, and product shelf-life. It is common practice to quantify the amount of water that a material sorbs at a given relative humidity (RH), but the results alone provide minimal to no physicochemical insight into water-solid interactions, without which pharmaceutical scientists cannot develop an understanding of their materials, so as to anticipate and circumvent potential problems. This research was conducted to advance the science of pharmaceutical materials by examining the thermodynamics of solids with sorbed water. The compounds studied include nonhygroscopic drugs, a channel hydrate drug, a stoichiometric hydrate excipient, and an amorphous excipient. The water sorption isotherms were measured over a range of temperature to extract the partial molar enthalpy and entropy of sorbed water as well as the same quantities for some of the solids. It was found that water-solid interactions spanned a range of energy and entropy as a function of RH, which was unique to the solid, and which could be valuable in identifying batch-to-batch differences and effects of processing in material performance. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Improved oral absorption of tacrolimus by a solid dispersion with hypromellose and sodium lauryl sulfate.

    Science.gov (United States)

    Jung, Hyuck Jun; Ahn, Hye In; Park, Ji Yeon; Ho, Myoung Jin; Lee, Dae Ro; Cho, Ha Ra; Park, Jun Seo; Choi, Yong Seok; Kang, Myung Joo

    2016-02-01

    A novel surfactant-incorporated hydroxypropyl methylcellulose (HPMC) solid dispersion (SD) system was constructed in order to facilitate the release rate and oral absorption of tacrolimus (FK506), a poorly water-soluble immunosuppressant. Several emulsifiers including sodium lauryl sulfate (SLS), as drug release promotors, were employed with HPMC to fabricate SD using the solvent wetting method. The solid state characteristics using differential scanning calorimetry and X-ray powder diffraction, revealed that FK506 was molecularly distributed within all dispersions in amorphous form. The dissolution rates of FK506 in SLS-incorporated SDs were much higher than those in SDs prepared with HPMC alone, and even with stearoyl polyoxyl-32 glycerides or tocopheryl polyethylene glycol 1000 succinate. In particular, the greatest dissolution enhancement was obtained from the SD consisting of the drug, HPMC, and SLS in a weight ratio of 1:1:3, providing a 50-fold higher drug concentration within 15 min, compared with HPMC SD. In vivo absorption study in rats demonstrates that the optimized formula remarkably increased the oral absorption of FK506, providing about 4.0-fold greater bioavailability (p<0.05) compared with the marketed product (Prograf®, Astellas Pharma). These data suggest that a novel SLS/HPMC SD may be an advantageous dosage form of FK506, boosting the dissolution and absorption in gastrointestinal tract. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Revealing facts behind spray dried solid dispersion technology used for solubility enhancement

    Science.gov (United States)

    Patel, Bhavesh B.; Patel, Jayvadan K.; Chakraborty, Subhashis; Shukla, Dali

    2013-01-01

    Poor solubility and bioavailability of an existing or newly synthesized drug always pose challenge in the development of efficient pharmaceutical formulation. Numerous technologies can be used to improve the solubility and among them amorphous solid dispersion based spray drying technology can be successfully useful for development of product from lab scale to commercial scale with a wide range of powder characteristics. Current review deals with the importance of spray drying technology in drug delivery, basically for solubility and bioavailability enhancement. Role of additives, selection of polymer, effect of process and formulation parameters, scale up optimization, and IVIVC have been covered to gain the interest of readers about the technology. Design of experiment (DoE) to optimize the spray drying process has been covered in the review. A lot more research work is required to evaluate spray drying as a technology for screening the right polymer for solid dispersion, especially to overcome the issue related to drug re-crystallization and to achieve a stable product both in vitro and in vivo. Based on the recent FDA recommendation, the need of the hour is also to adopt Quality by Design approach in the manufacturing process to carefully optimize the spray drying technology for its smooth transfer from lab scale to commercial scale. PMID:27134535

  19. Physicochemical characterization and dissolution enhancement of loratadine by solid dispersion technique

    International Nuclear Information System (INIS)

    Bandari, Suresh; Jadav, Subash; Eedara, Basanth Babu; Jukanti, Raju; Veerareddy, Prabhakar Reddy

    2013-01-01

    The purpose of this investigation was to enhance the dissolution rate of loratadine using polyethylene glycol 6000 (PEG) solid dispersions (SDs). The solubility behavior of loratadine in the presence of polyethylene glycol 4000 and polyethylene glycol 6000 in water showed linear increase with increasing concentrations of PEG, indicating A L type solubility diagrams. SDs of loratadine with PEG 6000 were prepared at 1 : 1, 1 : 3, 1 : 5, 1 : 7 and 1 : 9 ratios by the solvent evaporation method. Solid dispersions were characterized for drug content, dissolution behavior and for physicochemical characteristics. The dissolution rate of loratadine was enhanced rapidly with increasing concentrations of PEG 6000 in SDs. Fourier transform infrared (FTIR) studies showed the stability of loratadine and the absence of a well-defined loratadine - PEG 6000 interaction. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD) studies revealed the amorphous state of loratadine in SDs of loratadine with PEG 6000 which was further confirmed from scanning electron microscopy (SEM) studies. The flow properties of the blend, physical characteristics and disintegration time of the tablets formulated indicated that PEG 6000 SD can be used to formulate fast release loratadine tablets

  20. Physicochemical characterization and dissolution enhancement of loratadine by solid dispersion technique

    Energy Technology Data Exchange (ETDEWEB)

    Bandari, Suresh; Jadav, Subash; Eedara, Basanth Babu; Jukanti, Raju; Veerareddy, Prabhakar Reddy [St. Peter’s Institute of Pharmaceutical Sciences, Warangal (India)

    2013-01-15

    The purpose of this investigation was to enhance the dissolution rate of loratadine using polyethylene glycol 6000 (PEG) solid dispersions (SDs). The solubility behavior of loratadine in the presence of polyethylene glycol 4000 and polyethylene glycol 6000 in water showed linear increase with increasing concentrations of PEG, indicating A{sub L} type solubility diagrams. SDs of loratadine with PEG 6000 were prepared at 1 : 1, 1 : 3, 1 : 5, 1 : 7 and 1 : 9 ratios by the solvent evaporation method. Solid dispersions were characterized for drug content, dissolution behavior and for physicochemical characteristics. The dissolution rate of loratadine was enhanced rapidly with increasing concentrations of PEG 6000 in SDs. Fourier transform infrared (FTIR) studies showed the stability of loratadine and the absence of a well-defined loratadine - PEG 6000 interaction. Differential scanning calorimetry (DSC) and X-ray powder diffractometry (XRD) studies revealed the amorphous state of loratadine in SDs of loratadine with PEG 6000 which was further confirmed from scanning electron microscopy (SEM) studies. The flow properties of the blend, physical characteristics and disintegration time of the tablets formulated indicated that PEG 6000 SD can be used to formulate fast release loratadine tablets.

  1. Evaluation and enhancement of physical stability of semi-solid dispersions containing piroxicam into hard gelatin capsules.

    Science.gov (United States)

    Karataş, Ayşegül; Bekmezci, Serife

    2013-01-01

    The aim of the study was to investigate the physical stability of the semi-solid dispersions into the hard gelatine capsules prepared with Gelucire 44/14, Labrasol and different additives such as microcrystalline cellulose (MCC), mannitol and lactose (alpha-monohydrate) used for enhancing the stability of the formulations. The master dispersion prepared with only Gelucire 44/14 (20% w/w) and Labrasol (80% w/w) was stored in a refrigerator (5 +/- 3 degrees C), while the modified dispersions with the additives (2% w/w) were kept in a climatic chamber (25 +/- 2 degrees C / 60 +/- 5% RH) for 12 months. Dissolution tests of the semi-solid dispersions were performed in media with different pH's immediatly after preparation and after 3, 6 and 12 months of storage. FTIR and DSC studies were also carried out at the same time points. The ideal storage condition for the master dispersion was found to be at 5 degrees C. The addition of MCC, mannitol and lactose (alpha-monohydrate) to the original dispersion afforded a solidification effect on the formulation at room temperature and showed the same dissolution behavior (not less than 85% of piroxicam within 30 min in pH 1.2, 4.5 and 6.8; and water) with the master. The dispersion including lactose was stable at 25 degrees C for 12 months. However, the ideal period of storage for the modified dispersions including MCC and mannitol was 6 months at 25 degrees C. FTIR and DSC results both confirmed the amorphous state of piroxicam in all semi-solid dispersions under storage conditions for 12 months.

  2. Physical stabilization of low-molecular-weight amorphous drugs in the solid state: a material science approach.

    Science.gov (United States)

    Qi, Sheng; McAuley, William J; Yang, Ziyi; Tipduangta, Pratchaya

    2014-07-01

    Use of the amorphous state is considered to be one of the most effective approaches for improving the dissolution and subsequent oral bioavailability of poorly water-soluble drugs. However as the amorphous state has much higher physical instability in comparison with its crystalline counterpart, stabilization of amorphous drugs in a solid-dosage form presents a major challenge to formulators. The currently used approaches for stabilizing amorphous drug are discussed in this article with respect to their preparation, mechanism of stabilization and limitations. In order to realize the potential of amorphous formulations, significant efforts are required to enable the prediction of formulation performance. This will facilitate the development of computational tools that can inform a rapid and rational formulation development process for amorphous drugs.

  3. Solid dispersions: a strategy for poorly aqueous soluble drugs and technology updates.

    Science.gov (United States)

    Alam, Mohd Aftab; Ali, Raisuddin; Al-Jenoobi, Fahad Ibrahim; Al-Mohizea, Abdullah M

    2012-11-01

    Present article reviews solid dispersion (SD) technologies and other patented inventions in the area of pharmaceutical SDs, which provide stable amorphous SDs. The review briefly compiles different techniques for preparing SDs, their applications, characterization of SDs, types of SDs and also elaborates the carriers used to prepare SDs. The advantages of recently introduced SD technologies such as RightSize(™), closed-cycle spray drying (CSD), Lidose® are summarized. Stability-related issues like phase separation, re-crystallization and methods to curb these problems are also discussed. A patented carrier-screening tool for predicting physical stability of SDs on the basis of drug-carrier interaction is explained. Applications of SD technique in controlled drug delivery systems and cosmetics are explored. Review also summarizes the carriers such as Soluplus®, Neusilin®, Solumer(TM) used to prepare stable amorphous SD. Binary and ternary SDs are found to be more stable and provide better enhancement of solubility or dissolution of poorly water-soluble drugs. The use of surfactants in the carrier system of SD is a recent trend. Surfactants and polymers provide stability against re-crystallization of SDs, surfactants also improve solubility and dissolution of drug.

  4. Solid-state characterization and dissolution properties of meloxicam-moringa coagulant-PVP ternary solid dispersions.

    Science.gov (United States)

    Noolkar, Suhail B; Jadhav, Namdeo R; Bhende, Santosh A; Killedar, Suresh G

    2013-06-01

    The effect of ternary solid dispersions of poor water-soluble NSAID meloxicam with moringa coagulant (obtained by salt extraction of moringa seeds) and polyvinylpyrrolidone on the in vitro dissolution properties has been investigated. Binary (meloxicam-moringa and meloxicam-polyvinylpyrrolidone (PVP)) and ternary (meloxicam-moringa-PVP) systems were prepared by physical kneading and ball milling and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffractometry. The in vitro dissolution behavior of meloxicam from the different products was evaluated by means of United States Pharmacopeia type II dissolution apparatus. The results of solid-state studies indicated the presence of strong interactions between meloxicam, moringa, and PVP which were of totally amorphous nature. All ternary combinations were significantly more effective than the corresponding binary systems in improving the dissolution rate of meloxicam. The best performance in this respect was given by the ternary combination employing meloxicam-moringa-PVP ratio of [1:(3:1)] prepared by ball milling, with about six times increase in percent dissolution rate, whereas meloxicam-moringa (1:3) and meloxicam-PVP (1:4) prepared by ball milling improved dissolution of meloxicam by almost 3- and 2.5-folds, respectively. The achieved excellent dissolution enhancement of meloxicam in the ternary systems was attributed to the combined effects of impartation of hydrophilic characteristic by PVP, as well as to the synergistic interaction between moringa and PVP.

  5. Structural diversity of solid dispersions of acetylsalicylic acid as seen by solid-state NMR

    Czech Academy of Sciences Publication Activity Database

    Policianová, Olivia; Brus, Jiří; Hrubý, Martin; Urbanová, Martina; Zhigunov, Alexander; Kredatusová, Jana; Kobera, Libor

    2014-01-01

    Roč. 11, č. 2 (2014), s. 516-530 ISSN 1543-8384 R&D Projects: GA ČR GPP106/11/P426 Institutional support: RVO:61389013 Keywords : solid dispersions * acetylsalicylic acid * polymers Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 4.384, year: 2014

  6. Crosslinked hydrogels—a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs

    Directory of Open Access Journals (Sweden)

    Dajun D. Sun

    2014-02-01

    Full Text Available Water-insoluble materials containing amorphous solid dispersions (ASD are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate (PHEMA can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

  7. Crosslinked hydrogels-a promising class of insoluble solid molecular dispersion carriers for enhancing the delivery of poorly soluble drugs.

    Science.gov (United States)

    Sun, Dajun D; Lee, Ping I

    2014-02-01

    Water-insoluble materials containing amorphous solid dispersions (ASD) are an emerging category of drug carriers which can effectively improve dissolution kinetics and kinetic solubility of poorly soluble drugs. ASDs based on water-insoluble crosslinked hydrogels have unique features in contrast to those based on conventional water-soluble and water-insoluble carriers. For example, solid molecular dispersions of poorly soluble drugs in poly(2-hydroxyethyl methacrylate) (PHEMA) can maintain a high level of supersaturation over a prolonged period of time via a feedback-controlled diffusion mechanism thus avoiding the initial surge of supersaturation followed by a sharp decline in drug concentration typically encountered with ASDs based on water-soluble polymers. The creation of both immediate- and controlled-release ASD dosage forms is also achievable with the PHEMA based hydrogels. So far, ASD systems based on glassy PHEMA have been shown to be very effective in retarding precipitation of amorphous drugs in the solid state to achieve a robust physical stability. This review summarizes recent research efforts in investigating the potential of developing crosslinked PHEMA hydrogels as a promising alternative to conventional water-soluble ASD carriers, and a related finding that the rate of supersaturation generation does affect the kinetic solubility profiles implications to hydrogel based ASDs.

  8. A computer model for dispersed fluid-solid turbulent flows

    International Nuclear Information System (INIS)

    Liu, C.H.; Tulig, T.J.

    1985-01-01

    A computer model is being developed to simulate two-phase turbulent flow phenomena in fluids containing finely dispersed solids. The model is based on a dual-continuum picture of the individual phases and an extension of a two-equation turbulence closure theory. The resulting set of nonlinear partial differential equations are solved using a finite difference procedure with special treatment to promote convergence. The model has been checked against a number of idealized flow problems with known solutions. The authors are currently comparing model predictions with measurements to determine a proper set of turbulence parameters needed for simulating two-phase turbulent flows

  9. An Amorphous Network Model for Capillary Flow and Dispersion in a Partially Saturated Porous Medium

    Science.gov (United States)

    Simmons, C. S.; Rockhold, M. L.

    2013-12-01

    Network models of capillary flow are commonly used to represent conduction of fluids at pore scales. Typically, a flow system is described by a regular geometric lattice of interconnected tubes. Tubes constitute the pore throats, while connection junctions (nodes) are pore bodies. Such conceptualization of the geometry, however, is questionable for the pore scale, where irregularity clearly prevails, although prior published models using a regular lattice have demonstrated successful descriptions of the flow in the bulk medium. Here a network is allowed to be amorphous, and is not subject to any particular lattice structure. Few network flow models have treated partially saturated or even multiphase conditions. The research trend is toward using capillary tubes with triangular or square cross sections that have corners and always retain some fluid by capillarity when drained. In contrast, this model uses only circular capillaries, whose filled state is controlled by a capillary pressure rule for the junctions. The rule determines which capillary participate in the flow under an imposed matric potential gradient during steady flow conditions. Poiseuille's Law and Laplace equation are used to describe flow and water retention in the capillary units of the model. A modified conjugate gradient solution for steady flow that tracks which capillary in an amorphous network contribute to fluid conduction was devised for partially saturated conditions. The model thus retains the features of classical capillary models for determining hydraulic flow properties under unsaturated conditions based on distribution of non-interacting tubes, but now accounts for flow exchange at junctions. Continuity of the flow balance at every junction is solved simultaneously. The effective water retention relationship and unsaturated permeability are evaluated for an extensive enough network to represent a small bulk sample of porous medium. The model is applied for both a hypothetically

  10. Building solids inside nano-space: from confined amorphous through confined solvate to confined 'metastable' polymorph.

    Science.gov (United States)

    Nartowski, K P; Tedder, J; Braun, D E; Fábián, L; Khimyak, Y Z

    2015-10-14

    The nanocrystallisation of complex molecules inside mesoporous hosts and control over the resulting structure is a significant challenge. To date the largest organic molecule crystallised inside the nano-pores is a known pharmaceutical intermediate - ROY (259.3 g mol(-1)). In this work we demonstrate smart manipulation of the phase of a larger confined pharmaceutical - indomethacin (IMC, 357.8 g mol(-1)), a substance with known conformational flexibility and complex polymorphic behaviour. We show the detailed structural analysis and the control of solid state transformations of encapsulated molecules inside the pores of mesoscopic cellular foam (MCF, pore size ca. 29 nm) and controlled pore glass (CPG, pore size ca. 55 nm). Starting from confined amorphous IMC we drive crystallisation into a confined methanol solvate, which upon vacuum drying leads to the stabilised rare form V of IMC inside the MCF host. In contrast to the pure form, encapsulated form V does not transform into a more stable polymorph upon heating. The size of the constraining pores and the drug concentration within the pores determine whether the amorphous state of the drug is stabilised or it recrystallises into confined nanocrystals. The work presents, in a critical manner, an application of complementary techniques (DSC, PXRD, solid-state NMR, N2 adsorption) to confirm unambiguously the phase transitions under confinement and offers a comprehensive strategy towards the formation and control of nano-crystalline encapsulated organic solids.

  11. Controlled release systems containing solid dispersions: strategies and mechanisms.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun Bom; Lee, Beom-Jin

    2011-10-01

    In addition to a number of highly soluble drugs, most new chemical entities under development are poorly water-soluble drugs generally characterized by an insufficient dissolution rate and a small absorption window, leading to the low bioavailability. Controlled-release (CR) formulations have several potential advantages over conventional dosage forms, such as providing a uniform and prolonged therapeutic effect to improve patient compliance, reducing the frequency of dosing, minimizing the number of side effects, and reducing the strength of the required dose while increasing the effectiveness of the drug. Solid dispersions (SD) can be used to enhance the dissolution rate of poorly water-soluble drugs and to sustain the drug release by choosing an appropriate carrier. Thus, a CR-SD comprises both functions of SD and CR for poorly water-soluble drugs. Such CR dosage forms containing SD provide an immediately available dose for an immediate action followed by a gradual and continuous release of subsequent doses to maintain the plasma concentration of poorly water-soluble drugs over an extended period of time. This review aims to summarize all currently known aspects of controlled release systems containing solid dispersions, focusing on the preparation methods, mechanisms of action and characterization of physicochemical properties of the system.

  12. Solid-state amorphization in the Ni-Zr system investigated by positron lifetime spectroscopy

    International Nuclear Information System (INIS)

    Bernal, M.J.; De La Cruz, R.M.; Leguey, T.; Pareja, R.; Riveiro, J.M.

    1995-01-01

    The process of mechanical alloying and amorphization of Ni-Zr powders is investigated by positron lifetime spectroscopy, X-ray diffraction and differential scanning calorimetry. The short-lived component of the lifetime spectra is composition and milling-time dependent. The second lifetime component, found during the initial stages of the milling process, appears to be due to annihilation from states trapped at crystalline interface joints. The results indicate that the solid-state reactions induced by ball milling involve the transformation and disappearance of the crystalline interface joints in the powder particles. (orig.)

  13. The kinetics of solid phase epitaxy in As-doped buried amorphous silicon layers

    International Nuclear Information System (INIS)

    McCallum, J.C.

    1999-01-01

    Ion implantation is the principal method used to introduce dopants into silicon for fabrication of semiconductor devices. During ion implantation, damage accumulates in the crystalline silicon lattice and amorphisation may occur over the depth range of the ions if the implant dose is sufficiently high. As device dimensions shrink, the need to produce shallower and shallower highly-doped layers increases and the probability of amorphisation also increases. To achieve dopant-activation, the amorphous or damaged material must be returned to the crystalline state by thermal annealing. Amorphous silicon layers can be crystallised by the solid-state process of solid phase epitaxy (SPE) in which the amorphous layer transforms to crystalline silicon (c-Si) layer by layer using the underlying c-Si as a seed. The atomic mechanism that is responsible for the crystallisation is thought to involve highly-localised bond-breaking and rearrangement processes at the amorphous/crystalline (a/c) interface but the defect responsible for these bond rearrangements has not yet been identified. Since the bond breaking process necessarily generates dangling bonds, it has been suggested that the crystallisation process may solely involve the formation and migration of dangling bonds at the interface. One of the key factors which may shed further light on the nature of the SPE defect is the observed dopant-dependence of the rate of crystallisation. It has been found that moderate concentrations of dopants enhance the SPE crystallisation rate while the presence of equal concentrations of an n-type and a p-type dopant (impurity compensation) returns the SPE rate to the intrinsic value. This provides crucial evidence that the SPE mechanism is sensitive to the position of the Fermi level in the bandgap of the crystalline and/or the amorphous silicon phases and may lead to identification of an energy level within the bandgap that can be associated with the defect. This paper gives details of SPE

  14. Solid-State Electrochromic Device Consisting of Amorphous WO3 and Various Thin Oxide Layers

    Science.gov (United States)

    Shizukuishi, Makoto; Shimizu, Isamu; Inoue, Eiichi

    1980-11-01

    A mixed oxide containing Cr2O3 was introduced into an amorphous WO3 solid-state electrochromic device (ECD) in order to improve its colour memory effect. The electrochromic characteristics were greatly affected by the chemical constituents of a dielectric layer on the a-WO3 layer. Particularly, long memory effect and low power dissipation were attained in a solid-state ECD consisting of a-WO3 and Cr2O3\\cdotV2O5(50 wt.%). Some electrochromic characteristics of the a-WO3/Cr2O3\\cdotV2O5 ECD and the role of V2O5 were investigated.

  15. Solid-state, triboelectrostatic and dissolution characteristics of spray-dried piroxicam-glucosamine solid dispersions.

    Science.gov (United States)

    Adebisi, Adeola O; Kaialy, Waseem; Hussain, Tariq; Al-Hamidi, Hiba; Nokhodchi, Ali; Conway, Barbara R; Asare-Addo, Kofi

    2016-10-01

    This work explores the use of both spray drying and d-glucosamine HCl (GLU) as a hydrophilic carrier to improve the dissolution rate of piroxicam (PXM) whilst investigating the electrostatic charges associated with the spray drying process. Spray dried PXM:GLU solid dispersions were prepared and characterised (XRPD, DSC, SEM). Dissolution and triboelectric charging were also conducted. The results showed that the spray dried PXM alone, without GLU produced some PXM form II (DSC results) with no enhancement in solubility relative to that of the parent PXM. XRPD results also showed the spray drying process to decrease the crystallinity of GLU and solid dispersions produced. The presence of GLU improved the dissolution rate of PXM. Spray dried PXM: GLU at a ratio of 2:1 had the most improved dissolution. The spray drying process generally yielded PXM-GLU spherical particles of around 2.5μm which may have contributed to the improved dissolution. PXM showed a higher tendency for charging in comparison to the carrier GLU (-3.8 versus 0.5nC/g for untreated material and -7.5 versus 3.1nC/g for spray dried materials). Spray dried PXM and spray dried GLU demonstrated higher charge densities than untreated PXM and untreated GLU, respectively. Regardless of PXM:GLU ratio, all spray dried PXM:GLU solid dispersions showed a negligible charge density (net-CMR: 0.1-0.3nC/g). Spray drying of PXM:GLU solid dispersions can be used to produce formulation powders with practically no charge and thereby improving handling as well as dissolution behaviour of PXM. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. Solubilization of poorly water-soluble drugs using solid dispersions.

    Science.gov (United States)

    Tran, Thao T-D; Tran, Phuong H-L; Khanh, Tran N; Van, Toi V; Lee, Beom-Jin

    2013-08-01

    Many new drugs have been discovered in pharmaceutical industry and exposed their surprised potential therapeutic effects. Unfortunately, these drugs possess low absorption and bioavailability since their solubility limitation in water. Solid dispersion (SD) is the current technique gaining so many attractions from scientists due to its effect on improving solubility and dissolution rate of poorly water-soluble drugs. A number of patents including the most recent inventions have been undertaken in this review to address various respects of this strategy in solubilization of poorly watersoluble drugs including type of carriers, preparation methods and view of technologies used to detect SD properties and mechanisms with the aim to accomplish a SD not only effective on enhanced bioavailability but also overcome difficulties associated with stability and production. Future prospects are as well discussed with an only hope that many developments and researches in this field will be successfully reached and contributed to commercial use for treatment as much as possible.

  17. Preparation and characterization of etoricoxib solid dispersions using lipid carriers by spray drying technique

    OpenAIRE

    Chauhan, Bhaskar; Shimpi, Shyam; Paradkar, Anant

    2005-01-01

    The basic objectives of this study were to prepare and characterize solid dispersions of poorly water-soluble drug etoricoxib using lipid carriers by spray drying technique. The properties of solid dispersions were studied by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), differential scanning calorimetry (DSC), hotstage microscopy (HSM), radiograph powder diffraction (XRPD), and dissolution studies. The absence of etoricoxib peaks in XRPD profiles of solid dispersions ...

  18. Solid dispersion application in pharmaceutical technology: Methods of preparation and characterization

    OpenAIRE

    Medarević, Đorđe; Ibrić, Svetlana; Đuriš, Jelena; Đurić, Zorica

    2013-01-01

    A growing number of newly synthesized drugs exhibit low aqueous solubility, leading to poor bioavailability. Therefore, improving drug solubility and dissolution rate became one of the greatest challenges during formulation development. Solid dispersions formulation is one of the commonly investigated techniques for improving solubility of poorly soluble drugs. Solid dispersions are dispersions of one or more drugs in an inert carrier (matrix) in the solid state prepared by melting, solvent, ...

  19. FORMULATION AND EVALUATION OF MEFENAMIC ACID SOLID DISPERSIONS USING PEG-4000

    OpenAIRE

    Shaik Jamal Shariff; Shaik Saleem; Alaparthi Naga Pavan Kumar; Bachupally Ajay Kumar; Punuru Madhusudhan

    2013-01-01

    Mefenamic acid (MA) solid Dispersions were prepared employing methanol as a common solvent using PEG-4000 as a drug carrier with two different techniques namely, melting method and solvent evaporation in varied ratios. The prepared solid dispersions were evaluated and compared with that of pure drug (mefenamic acid) in respect to the dissolution rate and dissolution efficiency. It is noted that solid dispersions of mefenamic acid showed a remarkable increase in dissolution rate and dissolutio...

  20. Solid dispersions enhance solubility, dissolution, and permeability of thalidomide.

    Science.gov (United States)

    Barea, Silvana A; Mattos, Cristiane B; Cruz, Ariadne C C; Chaves, Vitor C; Pereira, Rafael N; Simões, Claudia M O; Kratz, Jadel M; Koester, Letícia S

    2017-03-01

    Thalidomide (THD) is a BCS class II drug with renewed and growing therapeutic applicability. Along with the low aqueous solubility, additional poor biopharmaceutical properties of the drug, i.e. chemical instability, high crystallinity, and polymorphism, lead to a slow and variable oral absorption. In this view, we developed solid dispersions (SDs) containing THD dispersed in different self-emulsifying carriers aiming at an enhanced absorption profile for the drug. THD was dispersed in lauroyl macrogol-32 glycerides (Gelucire ® 44/14) and α-tocopherol polyethylene glycol succinate (Kolliphor ® TPGS), in the presence or absence of the precipitation inhibitor polyvinylpyrrolidone K30 (PVP K30), by means of the solvent method. Physicochemical analysis revealed the formation of semicrystalline SDs. X-ray diffraction and infrared spectroscopy analyses suggest that the remaining crystalline fraction of the drug in the SDs did not undergo polymorphic transition. The impact of the solubility-enhancing formulations on the THD biopharmaceutical properties was evaluated by several in vitro techniques. The developed SDs were able to increase the apparent solubility of the drug (up to 2-3x the equilibrium solubility) for a least 4 h. Dissolution experiments (paddle method, 75 rpm) in different pHs showed that around 80% of drug dissolved after 120 min (versus 40% of pure crystalline drug). Additionally, we demonstrated the enhanced solubility obtained via SDs could be translated into increased flux in a parallel artificial membrane permeability assay (PAMPA). In summary, the results demonstrate that SDs could be considered an interesting and unexplored strategy to improve the biopharmaceutical properties of THD, since SDs of this important drug have yet to be reported.

  1. A novel and alternative approach to controlled release drug delivery system based on solid dispersion technique

    Directory of Open Access Journals (Sweden)

    Tapan Kumar Giri

    2012-12-01

    Full Text Available The solid dispersion method was originally used to improve the dissolution properties and the bioavailability of poorly water soluble drugs by dispersing them into water soluble carriers. In addition to the above, dissolution retardation through solid dispersion technique using water insoluble and water swellable polymer for the development of controlled release dosage forms has become a field of interest in recent years. Development of controlled release solid dispersion has a great advantage for bypassing the risk of a burst release of drug; since the structure of the solid dispersion is monolithic where drug molecules homogeneously disperse. Despite the remarkable potential and extensive research being conducted on controlled release solid dispersion system, commercialization and large scale production are limited. The author expects that recent technological advances may overcome the existing limitations and facilitate the commercial utilization of the techniques for manufacture of controlled release solid dispersions. This article begins with an overview of the different carriers being used for the preparation of controlled release solid dispersion and also different techniques being used for the purpose. Kinetics of drug release from these controlled release solid dispersions and the relevant mathematical modeling have also been reviewed in this manuscript.

  2. [Response surface method optimize of nano-silica solid dispersion technology assistant enzymatic hydrolysis preparation genistein].

    Science.gov (United States)

    Jin, Xin; Zhang, Zhen-Hai; Zhu, Jing; Sun, E; Yu, Dan-Hong; Chen, Xiao-Yun; Liu, Qi-Yuan; Ning, Qing; Jia, Xiao-Bin

    2012-04-01

    This article reports that nano-silica solid dispersion technology was used to raise genistein efficiency through increasing the enzymatic hydrolysis rate. Firstly, genistin-nano-silica solid dispersion was prepared by solvent method. And differential scanning calorimetry (DSC) and transmission electron microscopy (TEM) were used to verify the formation of solid dispersion, then enzymatic hydrolysis of solid dispersion was done by snailase to get genistein. With the conversion of genistein as criteria, single factor experiments were used to study the different factors affecting enzymatic hydrolysis of genistin and its solid dispersion. And then, response surface method was used to optimize of nano-silica solid dispersion technology assistant enzymatic hydrolysis. The optimum condition to get genistein through enzymatic hydrolysis of genistin-nano-silica solid dispersion was pH 7.1, temperature 52.2 degrees C, enzyme concentration 5.0 mg x mL(-1) and reaction time 7 h. Under this condition, the conversion of genistein was (93.47 +/- 2.40)%. Comparing with that without forming the genistin-nano-silica solid dispersion, the conversion increased 2.62 fold. At the same time, the product of hydrolysis was purified to get pure genistein. The method of enzymatic hydrolysis of genistin-nano-silica solid dispersion by snailase to obtain genistein is simple, efficiency and suitable for the modern scale production.

  3. Weak and Strong Gels and the Emergence of the Amorphous Solid State

    Directory of Open Access Journals (Sweden)

    Jack F. Douglas

    2018-02-01

    Full Text Available Gels are amorphous solids whose macroscopic viscoelastic response derives from constraints in the material that serve to localize the constituent molecules or particles about their average positions in space. These constraints may either be local in nature, as in chemical cross-linking and direct physical associations, or non-local, as in case of topological “entanglement” interactions between highly extended fiber or sheet structures in the fluid. Either of these interactions, or both combined, can lead to “gelation” or “amorphous solidification”. While gels are often considered to be inherently non-equilibrium materials, and correspondingly termed “soft glassy matter”, this is not generally the case. For example, the formation of vulcanized rubbers by cross-linking macromolecules can be exactly described as a second order phase transition from an equilibrium fluid to an equilibrium solid state, and amorphous solidification also arises in diverse physical gels in which molecular and particle localization occurs predominantly through transient molecuar associations, or even topological interactions. As equilibrium, or near equilibrium systems, such gels can be expected to exhibit universal linear and non-linear viscoelastic properties, especially near the “critical” conditions at which the gel state first emerges. In particular, a power-law viscoelastic response is frequently observed in gel materials near their “gelation” or “amorphous solidification” transition. Another basic property of physical gels of both theoretical and practical interest is their response to large stresses at constant shear rate or under a fixed macrocopic strain. In particular, these materials are often quite sensitive to applied stresses that can cause the self-assembled structure to progressively break down under flow or deformation. This disintegration of gel structure can lead to “yield” of the gel material, i.e., a fluidization

  4. Axial dispersion of gas and solid phases in a gas—solid packed column at trickle flow

    NARCIS (Netherlands)

    Roes, A.W.M.; van Swaaij, Willibrordus Petrus Maria

    1979-01-01

    Axial dispersion of gas and solid phases in a gas—solid packed column at trickle flow, a promising new countercurrent operation, was evaluated using residence time distribution (RTD) experiments. The column was packed with dumped Pall rings, the gas phase was air at ambient conditions and the solid

  5. Neutron Scattering Analysis of Water's Glass Transition and Micropore Collapse in Amorphous Solid Water.

    Science.gov (United States)

    Hill, Catherine R; Mitterdorfer, Christian; Youngs, Tristan G A; Bowron, Daniel T; Fraser, Helen J; Loerting, Thomas

    2016-05-27

    The question of the nature of water's glass transition has continued to be disputed over many years. Here we use slow heating scans (0.4  K min^{-1}) of compact amorphous solid water deposited at 77 K and an analysis of the accompanying changes in the small-angle neutron scattering signal, to study mesoscale changes in the ice network topology. From the data we infer the onset of rotational diffusion at 115 K, a sudden switchover from nondiffusive motion and enthalpy relaxation of the network at 121  K, in excellent agreement with the glass transition onset deduced from heat capacity and dielectric measurements. This indicates that water's glass transition is linked with long-range transport of water molecules on the time scale of minutes and, thus, clarifies its nature. Furthermore, the slow heating rates combined with the high crystallization resistance of the amorphous sample allow us to identify the glass transition end point at 136 K, which is well separated from the crystallization onset at 144 K-in contrast to all earlier experiments in the field.

  6. Physicochemical properties of direct compression tablets with spray dried and ball milled solid dispersions of tadalafil in PVP-VA.

    Science.gov (United States)

    Wlodarski, K; Tajber, L; Sawicki, W

    2016-12-01

    The aim of this research was to develop immediate release tablets comprising solid dispersion (IRSDTs) of tadalafil (Td) in a vinylpyrrolidone and vinyl acetate block copolymer (PVP-VA), characterized by improved dissolution profiles. The solid dispersion of Td in PVP-VA (Td/PVP-VA) in a weight ratio of 1:1 (w/w) was prepared using two different processes i.e. spray drying and ball milling. While the former process has been well established in the formulation of IRSDTs the latter has not been exploited in these systems yet. Regardless of the preparation method, both Td/PVP-VA solid dispersions were amorphous as confirmed by PXRD, DSC and FTIR. However, different morphology of particles (SEM) resulted in differences in water apparent solubility and disk intrinsic dissolution rate (DIDR). Both solid dispersions and crystalline Td were successfully made into directly compressible tablets at three doses of Td, i.e. 2.5mg, 10mgand20mg, yielding nine different formulations (D 1 -D 9 ). Each of the lots met the requirements set by Ph.Eur. and was evaluated with respect to appearance, diameter, thickness, mass, hardness, friability, disintegration time and content of Td. IRSDTs performed as supersaturable formulations and had significantly improved water dissolution profiles in comparison with equivalent tablets containing crystalline Td and the marketed formulations. Tablets with both spray dried and ball milled Td/PVP-VA revealed the greatest improvement in dissolution depending on the investigated doses, i.e. 2.5mgand20mg, respectively. Also, dissolution of Td from Td/PVP-VA delivered in different forms occurred in the following order: powders>tablets>capsules. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Preparation of nickel-based amorphous alloys with finely dispersed lead and lead-bismuth particles and their superconducting properties

    International Nuclear Information System (INIS)

    Inoue, A.; Oguchi, M.; Harakawa, Y.; Masumoto, T.; Matsuzaki, K.

    1986-01-01

    The application of the melt-quenching technique to Ni-Si-B-Pb, Ni-P-B-Pb, Ni-Si-B-Pb-Bi and Ni-P-B-Pb-Bi alloys containing immiscible elements such as lead and bismuth has been tried and it has been found to result in the formation of a new type of material consisting of fine fcc Pb or hcp epsilon(Pb-Bi) + bct X(Pb-Bi) particles dispersed uniformly in the nickel-based amorphous matrix. The particle size and interparticle distance were 1 to 3 and 1 to 4 μm, respectively, for the lead phase, and less than 0.2 to 0.5 μm and 0.2 to 1.0 μm for the Pb-Bi phase. The uniform dispersion of such fine particles into the amorphous matrix was achieved in the composition range below about 6 at% Pb and 7 at% (Pb+Bi). Additionally, these amorphous alloys have been found to exhibit a superconductivity by the proximity effect of fcc Pb or epsilon(Pb-Bi) superconducting particles. The transition temperature Tsub(c) was in the range 6.8 to 7.5 K for the Ni-Si (or P)-B-Pb alloys and 8.6 to 8.8 K for the Ni-Si (or P)-B-Pb-Bi alloys. The upper critical field Hsub(c2) and the critical current density Jsub(c) for (Nisub(0.8)Psub(0.1)Bsub(0.1)) 95 Pb 3 Bi 2 at 4.2 K were, respectively, about 1.6 T and of the order of 7 x 10 7 Am -2 at zero applied field. (author)

  8. Acoustic and Seismic Dispersion in Complex Fluids and Solids

    Science.gov (United States)

    Goddard, Joe

    2017-04-01

    The first part of the present paper is the continuation of a previous work [3] on the effects of higher spatial gradients and temporal relaxation on stress and heat flux in complex fluids. In particular, the general linear theory is applied to acoustic dispersion, extending a simpler model proposed by Davis and Brenner [2]. The theory is applied to a linearized version of the Chapman-Enskog fluid [1] valid to terms of Burnett order and including Maxwell-Cataneo relaxation of stress and heat flux on relaxation time scales τ. For this model, the dispersion relation k(ω) giving spatial wave number k as function of temporal frequency ω is a cubic in k2, in contrast to the quadratic in k2 given by the classical model and the recently proposed modification [2]. The cubic terms are shown to be important only for ωτ = O(1) where Maxwell-Cataneo relaxation is also important. As a second part of the present work, it is shown how the above model can also be applied to isotropic solids, where both shear and pressure waves are important. Finally, consideration is given to hyperstress in micro- polar continua, including both graded and micro-morphic varieties. [1]S. Chapman and T. Cowling. The mathematical theory of non-uniform gases. Cambridge University Press, [Cambridge, UK], 1960. [2]A. M.J. Davis and H. Brenner. Thermal and viscous effects on sound waves: revised classical theory. J. Acoust. Soc. Am., 132(5):2963-9, 2012. [3] J.D. Goddard. On material velocities and non-locality in the thermo-mechanics of continua. Int. J. Eng. Sci., 48(11):1279-88, 2010.

  9. Quantifying atom addition reactions on amorphous solid water: a review of recent laboratory advances

    Science.gov (United States)

    He, Jiao; Vidali, Gianfranco

    2018-06-01

    Complex organic molecules found in space are mostly formed on and in the ice mantle covering interstellar dust grains. In clouds where ionizing irradiation is insignificant, chemical reactions on the ice mantle are dominated by thermal processes. Modeling of grain surface chemistry requires detailed information from the laboratory, including sticking coefficients, binding energies, diffusion energy barriers, mechanism of reaction, and chemical desorption rates. In this talk, recent laboratory advances in obtaining these information would be reviewed. Specifically, this talk will focus on the efforts in our group in: 1) Determining the mechanism of atomic hydrogen addition reactions on amorphous solid water (ASW); 2) Measuring the chemical desorption coefficient of H+O3-->O2+OH using the time-resolved scattering technique; and 3) Measuring the diffusion energy barrier of volatile molecules on ASW. Further laboratory studies will be suggested.This research was supported by NSF Astronomy & Astrophysics Research Grant #1615897.

  10. Direct conversion of radioactive and chemical waste containing metals, ceramics, amorphous solids, and organics to glass

    International Nuclear Information System (INIS)

    Forsberg, C.W.; Beahm, E.C.; Parker, G.W.

    1994-01-01

    The Glass Material Oxidation and Dissolution System (CMODS) is a new process for direct conversion of radioactive, mixed, and chemical wastes to glass. The wastes can be in the chemical forms of metals, ceramics, amorphous solids, and organics. GMODS destroys organics and it incorporates heavy metals and radionuclides into a glass. Processable wastes may include miscellaneous spent fuels (SF), SF hulls and hardware, plutonium wastes in different forms, high-efficiency particulate air (HEPA) filters, ion-exchange resins, failed equipment, and laboratory wastes. Thermodynamic calculations indicate theoretical feasibility. Small-scale laboratory experiments (< 100 g per test) have demonstrated chemical laboratory feasibility for several metals. Additional work is needed to demonstrate engineering feasibility

  11. Preparation, characterization, and dissolution studies of naproxen solid dispersions using polyethylene glycol 6000 and labrafil M2130

    Directory of Open Access Journals (Sweden)

    Jafar Akbari

    2015-06-01

    Full Text Available Naproxen is a poor water soluble, non-steroidal analgesic and anti-inflammatory drug. The enhancement of oral bioavailability of poor water soluble drugs remains one of the most challenging aspects of drug development. Although salt formation, solubilization and particle size reduction have commonly been used to increase dissolution rate and thereby oral absorption and bioavailability of low water soluble drugs, there are practical limitation of these techniques. However, the most attractive option for increasing the release rate is improvement of solubility through formulation approaches. In this study, solid dispersions (SD of naproxen were prepared by hot melt method using various ratios of drug to polymers (PEG6000 separately and characterized for physical appearance, FTIR, DSC, X-Ray crystallography, and in-vitro dissolution studies. The influence of several amounts of Labrafil M2130 was also studied. FTIR study revealed that drug was stable in SDs, and great state of amorphous formed particles was proofed by DSC analysis. The in vitro dissolution studies were carried using USP type II (paddle dissolution apparatus at medium (pH 1.5. Solubility of naproxen from SDs was increased in dissolution media. The prepared dispersion showed increase in the dissolution rate of naproxen comparing to that of physical mixtures of drug and polymers and pure drug. Percent of drug released in 60 minutes was 23.92% for pure naproxen witch is increased in SDs and reached to100% for best formulations of PEG6000 and labrafil based SDs respectively, considering ratio of drug to polymers.It is concluded that dissolution of the naproxen could be improved by the solid dispersion. Although physical mixtures have increased the rate of dissolution, dissolution shows faster release from SDs which would therefore be due to formation of amorphous particles through the hot melt process which was also revealed by DSC analysis and XRD.

  12. Preparation and pharmacokinetic evaluation of curcumin solid dispersion using Solutol® HS15 as a carrier.

    Science.gov (United States)

    Seo, Sang-Wan; Han, Hyo-Kyung; Chun, Myung-Kwan; Choi, Hoo-Kyun

    2012-03-15

    Solubility of curcumin at physiological pH was significantly increased by forming solid dispersion (SD) with Solutol® HS15. Since curcumin undergoes hydrolytic degradation, chemical stability study was conducted in pH 1.2, 6.8 and 7.4 buffer media. Solutol® HS15 exhibited superior stabilizing effect to Cremophor® RH40 and Kollidon® 30. The physical state of the dispersed curcumin in the polymer matrix was characterized by differential scanning calorimetry and X-ray diffraction studies. SD preparation transformed curcumin into amorphous form and facilitated micellar incorporation, thereby preventing hydrolysis in aqueous medium. In vitro drug release in pH 6.8 buffer revealed that SD (1:10) improved the dissolution of curcumin with approximately 90% release of the drug within 1h. Pharmacokinetic study of the solid dispersion formulation in rat showed that bioavailability of the drug was significantly improved as compared to pure curcumin. SD containing 1:10 ratio of drug and Solutol® HS15 resulted in approximately 5 fold higher AUC(0-12h). SD formulation was physically stable over the study period of 3 months. Copyright © 2011 Elsevier B.V. All rights reserved.

  13. Understanding API-polymer proximities in amorphous stabilized composite drug products using fluorine-carbon 2D HETCOR solid-state NMR.

    Science.gov (United States)

    Abraham, Anuji; Crull, George

    2014-10-06

    A simple and robust method for obtaining fluorine-carbon proximities was established using a (19)F-(13)C heteronuclear correlation (HETCOR) two-dimensional (2D) solid-state nuclear magnetic resonance (ssNMR) experiment under magic-angle spinning (MAS). The method was applied to study a crystalline active pharmaceutical ingredient (API), avagacestat, containing two types of fluorine atoms and its API-polymer composite drug product. These results provide insight into the molecular structure, aid with assigning the carbon resonances, and probe API-polymer proximities in amorphous spray dried dispersions (SDD). This method has an advantage over the commonly used (1)H-(13)C HETCOR because of the large chemical shift dispersion in the fluorine dimension. In the present study, fluorine-carbon distances up to 8 Å were probed, giving insight into the API structure, crystal packing, and assignments. Most importantly, the study demonstrates a method for probing an intimate molecular level contact between an amorphous API and a polymer in an SDD, giving insights into molecular association and understanding of the role of the polymer in API stability (such as recrystallization, degradation, etc.) in such novel composite drug products.

  14. Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique.

    Science.gov (United States)

    Patel, S M; Patel, R P; Prajapati, B G

    2012-03-01

    The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4). Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

  15. Solubility enhancement of benfotiamine, a lipid derivative of thiamine by solid dispersion technique

    Directory of Open Access Journals (Sweden)

    S M Patel

    2012-01-01

    Full Text Available The present study was aimed to increase the solubility of the poorly water soluble drug benfotiamine using hydrophilic polymers (PVP K-30 and HPMC E4. Solid dispersions were prepared by kneading method. Phase solubility study, in-vitro dissolution of pure drug, physical mixtures and solid dispersions were carried out. PVP and HPMC were found to be effective in increasing the dissolution of Benfotiamine in solid dispersions when compared to pure drug. FT-IR, differential scanning calorimetry and X-ray diffractometry studies were carried out in order to characterize the drug and solid dispersion. To conclude that, the prepared solid dispersion of PVP-30 may to effectively used for the enhancement of solubility of poorly water soluble drugs such as benfotiamine.

  16. Modeling solid-fuel dispersal during slow loss-of-flow-type transients

    International Nuclear Information System (INIS)

    DiMelfi, R.J.; Fenske, G.R.

    1981-01-01

    The dispersal, under certain accident conditions, of solid particles of fast-reactor fuel is examined in this paper. In particular, we explore the possibility that solid-fuel fragmentation and dispersal can be driven by expanding fission gas, during a slow LOF-type accident. The consequences of fragmentation are studied in terms of the size and speed of dispersed particles, and the overall quantity of fuel moved. (orig.)

  17. Fabrication of amorphous Si and C anode films via co-sputtering for an all-solid-state battery

    Energy Technology Data Exchange (ETDEWEB)

    Lee, K.S. [Department of Materials Science and Engineering, Yonsei University Shinchondong, 262 Seongsanno, Seodaemoongu, Seoul 120-749 (Korea, Republic of); Department of Environment and Energy Engineering, Gachon University, Seongnamdaero 1342, 461-710 Gyeonggi-do (Korea, Republic of); Lee, S.H. [Department of Environment and Energy Engineering, Gachon University, Seongnamdaero 1342, 461-710 Gyeonggi-do (Korea, Republic of); Woo, S.P. [Department of Materials Science and Engineering, Yonsei University Shinchondong, 262 Seongsanno, Seodaemoongu, Seoul 120-749 (Korea, Republic of); Department of Environment and Energy Engineering, Gachon University, Seongnamdaero 1342, 461-710 Gyeonggi-do (Korea, Republic of); Kim, H.S. [Department of Mechanical Engineering, Gachon University, Seongnamdaero 1342, 461-710 Gyeonggi-do (Korea, Republic of); Yoon, Y.S., E-mail: benedicto@gachon.ac.kr [Department of Environment and Energy Engineering, Gachon University, Seongnamdaero 1342, 461-710 Gyeonggi-do (Korea, Republic of)

    2014-08-01

    In this study, a combination of silicon and carbon as the anode material for an all-solid-state battery has been investigated to overcome their individual deficiencies. The capacity of silicon thin films with an input power of 60 W shows dramatic failure after 38 cycles due to serious volume expansion. In contrast, C thin films at 60 W show high stability of cyclic performance and capacity retention. The amorphous silicon and carbon composite reduced the volume expansion of silicon during long term cycles and enhanced the low specific capacity of the carbon. This resistance of the volume expansion might be expected from the cushion effect caused by the carbon, which was confirmed by scanning electron microscope images after a 100 cycle test. These results indicate that amorphous silicon and carbon composite thin films have a high possibility as the stable anode material for an all-solid-state battery. - Highlights: • Amorphous Si/C nanocomposite thin films have been prepared by co-sputtering. • Carbon can act as a cushion effect to prevent volume expansion of Si. • Amorphous Si/C nanocomposite thin films show structure stability at 100 cycles. • Capacity of the amorphous Si/C nanocomposite thin films was enhanced considerably.

  18. Solubility enhancement of BCS Class II drug by solid phospholipid dispersions: Spray drying versus freeze-drying.

    Science.gov (United States)

    Fong, Sophia Yui Kau; Ibisogly, Asiye; Bauer-Brandl, Annette

    2015-12-30

    The poor aqueous solubility of BCS Class II drugs represents a major challenge for oral dosage form development. Using celecoxib (CXB) as model drug, the current study adopted a novel solid phospholipid nanoparticle (SPLN) approach and compared the effect of two commonly used industrial manufacturing methods, spray- and freeze-drying, on the solubility and dissolution enhancement of CXB. CXB was formulated with Phospholipoid E80 (PL) and trehalose at different CXB:PL:trehalose ratios, of which 1:10:16 was the optimal formulation. Spherical amorphous SPLNs with average diameters <1μm were produced by spray-drying; while amorphous 'matrix'-like structures of solid PL dispersion with larger particle sizes were prepared by freeze-drying. Formulations from both methods significantly enhanced the dissolution rates, apparent solubility, and molecularly dissolved concentration of CXB in phosphate buffer (PBS, pH 6.5) and in biorelevant fasted state simulated intestinal fluid (FaSSIF, pH 6.5) (p<0.05). While similar dissolution rates were found, the spray-dried SPLNs had a larger enhancement in apparent solubility (29- to 132-fold) as well as molecular solubility (18-fold) of CXB at equilibrium (p<0.05). The strong capability of the spray-dried SPLNs to attain 'true' supersaturation state makes them a promising approach for bioavailability enhancement of poorly soluble drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Elastic properties of amorphous boron suboxide based solids studied using ab initio molecular dynamics

    International Nuclear Information System (INIS)

    Music, Denis; Schneider, Jochen M

    2008-01-01

    We have studied the correlation between chemical composition, structure, chemical bonding and elastic properties of amorphous B 6 O based solids using ab initio molecular dynamics. These solids are of different chemical compositions, but the elasticity data appear to be a function of density. This is in agreement with previous experimental observations. As the density increases from 1.64 to 2.38 g cm -3 , the elastic modulus increases from 74 to 253 GPa. This may be understood by analyzing the cohesive energy and the chemical bonding of these compounds. The cohesive energy decreases from -7.051 to -7.584 eV/atom in the elastic modulus range studied. On the basis of the electron density distributions, Mulliken analysis and radial distribution functions, icosahedral bonding is the dominating bonding type. C and N promote cross-linking of icosahedra and thus increase the density, while H hinders the cross-linking by forming OH groups. The presence of icosahedral bonding is independent of the density

  20. Emerging trends in the stabilization of amorphous drugs.

    Science.gov (United States)

    Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J; Grohganz, Holger; Rades, Thomas

    2013-08-30

    The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative methods to amorphous polymer dispersions for stabilizing the amorphous form of drugs. First, an overview of the properties and stabilization mechanisms of amorphous forms is provided. Subsequently, formulation approaches such as the preparation of co-amorphous small-molecule mixtures and the use of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals. Copyright © 2012 Elsevier B.V. All rights reserved.

  1. Multiple Linear Regression Modeling To Predict the Stability of Polymer-Drug Solid Dispersions: Comparison of the Effects of Polymers and Manufacturing Methods on Solid Dispersion Stability.

    Science.gov (United States)

    Fridgeirsdottir, Gudrun A; Harris, Robert J; Dryden, Ian L; Fischer, Peter M; Roberts, Clive J

    2018-03-29

    Solid dispersions can be a successful way to enhance the bioavailability of poorly soluble drugs. Here 60 solid dispersion formulations were produced using ten chemically diverse, neutral, poorly soluble drugs, three commonly used polymers, and two manufacturing techniques, spray-drying and melt extrusion. Each formulation underwent a six-month stability study at accelerated conditions, 40 °C and 75% relative humidity (RH). Significant differences in times to crystallization (onset of crystallization) were observed between both the different polymers and the two processing methods. Stability from zero days to over one year was observed. The extensive experimental data set obtained from this stability study was used to build multiple linear regression models to correlate physicochemical properties of the active pharmaceutical ingredients (API) with the stability data. The purpose of these models is to indicate which combination of processing method and polymer carrier is most likely to give a stable solid dispersion. Six quantitative mathematical multiple linear regression-based models were produced based on selection of the most influential independent physical and chemical parameters from a set of 33 possible factors, one model for each combination of polymer and processing method, with good predictability of stability. Three general rules are proposed from these models for the formulation development of suitably stable solid dispersions. Namely, increased stability is correlated with increased glass transition temperature ( T g ) of solid dispersions, as well as decreased number of H-bond donors and increased molecular flexibility (such as rotatable bonds and ring count) of the drug molecule.

  2. Solid-phase extraction versus matrix solid-phase dispersion: Application to white grapes.

    Science.gov (United States)

    Dopico-García, M S; Valentão, P; Jagodziñska, A; Klepczyñska, J; Guerra, L; Andrade, P B; Seabra, R M

    2007-11-15

    The use of matrix solid-phase dispersion (MSPD) was tested to, separately, extract phenolic compounds and organic acids from white grapes. This method was compared with a more conventional analytical method previously developed that combines solid liquid extraction (SL) to simultaneously extract phenolic compounds and organic acids followed by a solid-phase extraction (SPE) to separate the two types of compounds. Although the results were qualitatively similar for both techniques, the levels of extracted compounds were in general quite lower on using MSPD, especially for organic acids. Therefore, SL-SPE method was preferred to analyse white "Vinho Verde" grapes. Twenty samples of 10 different varieties (Alvarinho, Avesso, Asal-Branco, Batoca, Douradinha, Esganoso de Castelo Paiva, Loureiro, Pedernã, Rabigato and Trajadura) from four different locations in Minho (Portugal) were analysed in order to study the effects of variety and origin on the profile of the above mentioned compounds. Principal component analysis (PCA) was applied separately to establish the main sources of variability present in the data sets for phenolic compounds, organic acids and for the global data. PCA of phenolic compounds accounted for the highest variability (77.9%) with two PCs, enabling characterization of the varieties of samples according to their higher content in flavonol derivatives or epicatechin. Additionally, a strong effect of sample origin was observed. Stepwise linear discriminant analysis (SLDA) was used for differentiation of grapes according to the origin and variety, resulting in a correct classification of 100 and 70%, respectively.

  3. Studies on Dissolution Enhancement of Prednisolone, a Poorly Water-Soluble Drug by Solid Dispersion Technique

    Directory of Open Access Journals (Sweden)

    Parvin Zakeri-Milani

    2011-06-01

    Full Text Available Introduction: Prednisolone is a class II substance according to the Biopharmaceutics Classification System. It is a poorly water soluble agent. The aim of the present study was to improve dissolution rate of a poorly water-soluble drug, prednisolone, by a solid dispersion technique. Methods: Solid dispersion of prednisolone was prepared with PEG 6000 or different carbohydrates such as lactose and dextrin with various ratios of the drug to carrier i.e., 1:10, 1:20 and 1:40. Solid dispersions were prepared by coevaporation method. The evaluation of the properties of the dispersions was performed using dissolution studies, Fourier-transform infrared spectroscopy and x-ray powder diffractometery. Results: The results indicated that lactose is suitable carriers to enhance the in vitro dissolution rate of prednisolone. The data from the x-ray diffraction showed that the drug was still detectable in its solid state in all solid dispersions except solid dispersions prepared by dextrin as carrier. The results from infrared spectroscopy showed no well-defined drug–carrier interactions for coevaporates. Conclusion: Solid dispersion of a poorly water-soluble drug, prednisolone may alleviate the problems of delayed and inconsistent rate of dissolution of the drug.

  4. Enhanced solubility and bioavailability of sibutramine base by solid dispersion system with aqueous medium.

    Science.gov (United States)

    Li, Dong Xun; Jang, Ki-Young; Kang, Wonku; Bae, Kyoungjin; Lee, Mann Hyung; Oh, Yu-Kyoung; Jee, Jun-Pil; Park, Young-Joon; Oh, Dong Hoon; Seo, Youn Gee; Kim, Young Ran; Kim, Jong Oh; Woo, Jong Soo; Yong, Chul Soon; Choi, Han-Gon

    2010-01-01

    To develop a novel sibutramine base-loaded solid dispersion with improved solubility bioavailability, various solid dispersions were prepared with water, hydroxypropylmethyl cellulose (HPMC), poloxamer and citric acid using spray-drying technique. The effect of HPMC, poloxamer and citric acid on the aqueous solubility of sibutramine was investigated. The physicochemical properties of solid dispersion were investigated using scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction. The dissolution and pharmacokinetics in rats of solid dispersion were evaluated compared to the sibutramine hydrochloride monohydrate-loaded commercial product (Reductil). The sibutramine base-loaded solid dispersion gave two type forms. Like conventional solid dispersion system, one type appeared as a spherical shape with smooth surface, as the carriers and drug with relatively low melting point were soluble in water and formed it. The other appeared as an irregular form with relatively rough surface. Unlike conventional solid dispersion system, this type changed no crystalline form of drug. Our results suggested that this type was formed by attaching hydrophilic carriers to the surface of drug without crystal change, resulting from changing the hydrophobic drug to hydrophilic form. The sibutramine-loaded solid dispersion at the weight ratio of sibutramine base/HPMC/poloxamer/citric acid of 5/3/3/0.2 gave the maximum drug solubility of about 3 mg/ml. Furthermore, it showed the similar plasma concentration, area under the curve (AUC) and C(max) of parent drug, metabolite I and II to the commercial product, indicating that it might give the similar drug efficacy compared to the sibutramine hydrochloride monohydrate-loaded commercial product in rats. Thus, this solid dispersion system would be useful to deliver poorly water-soluble sibutramine base with enhanced bioavailability.

  5. Flexible continuous manufacturing platforms for solid dispersion formulations

    Science.gov (United States)

    Karry-Rivera, Krizia Marie

    In 2013 16,000 people died in the US due to overdose from prescription drugs and synthetic narcotics. As of that same year, 90% of new molecular entities in the pharmaceutical drug pipeline are classified as poor water-soluble. The work in this dissertation aims to design, develop and validate platforms that solubilize weak acids and can potentially deter drug abuse. These platforms are based on processing solid dispersions via solvent-casting and hot-melt extrusion methods to produce oral transmucosal films and melt tablets. To develop these platforms, nanocrystalline suspensions and glassy solutions were solvent-casted in the form of films after physicochemical characterizations of drug-excipient interactions and design of experiment approaches. A second order model was fitted to the emulsion diffusion process to predict average nanoparticle size and for process optimization. To further validate the manufacturing flexibility of the formulations, glassy solutions were also extruded and molded into tablets. This process included a systematic quality-by-design (QbD) approach that served to identify the factors affecting the critical quality attributes (CQAs) of the melt tablets. These products, due to their novelty, lack discriminatory performance tests that serve as predictors to their compliance and stability. Consequently, Process Analytical Technology (PAT) tools were integrated into the continuous manufacturing platform for films. Near-infrared (NIR) spectroscopy, including chemical imaging, combined with deconvolution algorithms were utilized for a holistic assessment of the effect of formulation and process variables on the product's CQAs. Biorelevant dissolution protocols were then established to improve the in-vivo in-vitro correlation of the oral transmucosal films. In conclusion, the work in this dissertation supports the delivery of poor-water soluble drugs in products that may deter abuse. Drug nanocrystals ensured high bioavailability, while glassy

  6. Enhanced dissolution and bioavailability of biochanin A via the preparation of solid dispersion: in vitro and in vivo evaluation.

    Science.gov (United States)

    Han, Hyo-Kyung; Lee, Beom-Jin; Lee, Hyoung-Kyu

    2011-08-30

    The present study aimed to improve the bioavailability of biochanin A, a poorly soluble bioflavonoid, via the preparation of solid dispersion (SD) using Solutol HS15 and HPMC 2910. Solubility of biochanin A was enhanced by 8-60 folds as the drug-carrier ratio was increased in SDs. Furthermore, compared to pure biochanin A or physical mixture (PM), SDs significantly improved the dissolution rate and the extent of drug release. Particularly, SDs (Drug:Solutol HS15:HPMC 2910=1:5:5 or 1:10:10) achieved the rapid and complete drug release (approximately 100% within 1h) at pH 6.8. The XRD patterns indicated that SDs might enhance the solubility of biochanin A by changing the drug crystallinity to amorphous state in addition to the solubilizing effect of hydrophilic carriers. The improved dissolution of biochanin A via SD formulation appeared to be well correlated with the enhanced oral exposure of biochanin A in rats. After an oral administration of SD (Drug:Solutol HS15:HPMC 2910=1:10:10), C(max) and AUC of biochanin A were increased by approximately 13 and 5 folds, respectively, implying that SDs could be effective to improve the bioavailability of biochanin A. In conclusion, solid dispersion with Solutol HS15 and HPMC 2910 appeared to be promising to improve the dissolution and oral exposure of biochanin A. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Surface and bulk crystallization of amorphous solid water films: Confirmation of “top-down” crystallization

    Energy Technology Data Exchange (ETDEWEB)

    Yuan, Chunqing; Smith, R. Scott; Kay, Bruce D.

    2016-10-01

    The crystallization kinetics of nanoscale amorphous solid water (ASW) films are investigated using temperature-programmed desorption (TPD) and reflection absorption infrared spectroscopy (RAIRS). TPD measurements are used to probe surface crystallization and RAIRS measurements are used to probe bulk crystallization. Isothermal TPD results show that surface crystallization is independent of the film thickness (from 100 to 1000 ML). Conversely, the RAIRS measurements show that the bulk crystallization time increases linearly with increasing film thickness. These results suggest that nucleation and crystallization begin at the ASW/vacuum interface and then the crystallization growth front propagates linearly into the bulk. This mechanism was confirmed by selective placement of an isotopic layer (5% D2O in H2O) at various positions in an ASW (H2O) film. In this case, the closer the isotopic layer was to the vacuum interface, the earlier the isotopic layer crystallized. These experiments provide direct evidence to confirm that ASW crystallization in vacuum proceeds by a “top-down” crystallization mechanism.

  8. Small-angle neutron scattering study of micropore collapse in amorphous solid water.

    Science.gov (United States)

    Mitterdorfer, Christian; Bauer, Marion; Youngs, Tristan G A; Bowron, Daniel T; Hill, Catherine R; Fraser, Helen J; Finney, John L; Loerting, Thomas

    2014-08-14

    Vapor-deposited amorphous solid water (ASW) is the most abundant solid molecular material in space, where it plays a direct role in both the formation of more complex chemical species and the aggregation of icy materials in the earliest stages of planet formation. Nevertheless, some of its low temperature physics such as the collapse of the micropore network upon heating are still far from being understood. Here we characterize the nature of the micropores and their collapse using neutron scattering of gram-quantities of D2O-ASW of internal surface areas up to 230 ± 10 m(2) g(-1) prepared at 77 K. The model-free interpretation of the small-angle scattering data suggests micropores, which remain stable up to 120-140 K and then experience a sudden collapse. The exact onset temperature to pore collapse depends on the type of flow conditions employed in the preparation of ASW and, thus, the specific surface area of the initial deposit, whereas the onset of crystallization to cubic ice is unaffected by the flow conditions. Analysis of the small-angle neutron scattering signal using the Guinier-Porod model suggests that a sudden transition from three-dimensional cylindrical pores with 15 Å radius of gyration to two-dimensional lamellae is the mechanism underlying the pore collapse. The rather high temperature of about 120-140 K of micropore collapse and the 3D-to-2D type of the transition unraveled in this study have implications for our understanding of the processing and evolution of ices in various astrophysical environments.

  9. A basic insight into the stability and manufacturing aspects of solid dispersions

    Directory of Open Access Journals (Sweden)

    Jishnu Vijay

    2012-01-01

    Full Text Available The development of a bioavailable dosage form is the most challenging task for the researchers. In the arena of advanced drug delivery systems, the solid dispersion techniques seem to be a promising system for the development of an optimized, bioavailable formulation of Class 2 drugs. The methods of formulation of solid dispersion have been summarized. This article is an effort to define a solid dispersion and its classification. The prospective of the stability of solid dispersion has also been discussed. Moreover, the major techniques that have been used so far such as the fusion/melting method, solvent evaporation method, hot melt extrusion method, supercritical fluid methods, have also been detailed.

  10. Natural polymers: Best carriers for improving bioavailability of poorly water soluble drugs in solid dispersions

    OpenAIRE

    Sandip Sapkal; Mahesh Narkhede; Mukesh Babhulkar; Gautam Mehetre; Ashish Rathi

    2013-01-01

    ABSTRACTNatural polymers and its modified forms can be used as best alternative for improving bioavailabilityof poorly water soluble drugs in solid dispersion. Most of the natural polymersare hydrophilic and having high swelling capacity. Recent trend towards the use of naturalpolymer demands the replacement of synthetic additives with natural ones. Many plant derivednatural polymers are studied for use in solid dispersion systems, out of which naturalgums, cyclodextrin and carbohydrate are m...

  11. Dispersion of Silicate in Tricalcium Phosphate Elucidated by Solid-State NMR

    Energy Technology Data Exchange (ETDEWEB)

    Rewal, A.; Wei, X.; Akinc, M.; Schmidt-Rohr, K.

    2008-03-12

    The dispersion of silicate in tricalcium phosphate, a resorbable bioceramics for bone replacement, has been investigated by various solid-state nuclear magnetic resonance (NMR) methods. In samples prepared with 5 and 10 mol% of both {sup 29}SiO{sub 2} and ZnO, three types of silicate have been detected: (i) SiO{sub 4}{sup 4-} (Q{sub 0} sites) with long longitudinal (T{sub 1,Si}) relaxation times ({approx} 10,000 s), which substitute for {approx}1% of PO{sub 4}{sup 3-}; (ii) silicate nanoinclusions containing Q{sub 2}, Q{sub 1}, and Q{sub 0} sites with T{sub 1,Si} 100 s, which account for most of the silicon; and (iii) crystalline Q{sub 4} (SiO{sub 2}) with long T{sub 1,Si}. Sensitivity was enhanced >100-fold by {sup 29}Si enrichment and refocused detection. The inclusions in both samples have a diameter of {approx}8 nm, as proved by {sup 29}Si{l_brace}{sup 31}P{r_brace} REDOR dephasing on a 30-ms time scale, which was simulated using a multispin approach specifically suited for nanoparticles. {sup 29}Si CODEX NMR with 30-s {sup 29}Si spin diffusion confirms that an inclusion contains >10 Si (consistent with the REDOR result of >100 Si per inclusion). Overlapping signals of silicate Q{sub 2}, Q{sub 1}, and Q{sub 0} sites were spectrally edited based on their J-couplings, using double-quantum filtering. The large inhomogeneous broadening of the Q{sub 2}, Q{sub 1}, and Q{sub 0} {sup 29}Si subspectra indicates that the nanoinclusions are amorphous.

  12. Preparation and characterization of fast dissolving flurbiprofen and esomeprazole solid dispersion using spray drying technique.

    Science.gov (United States)

    Pradhan, Roshan; Tran, Tuan Hiep; Kim, Sung Yub; Woo, Kyu Bong; Choi, Yong Joo; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2016-04-11

    We aimed to develop an immediate-release flurbiprofen (FLU) and esomeprazole (ESO) combination formulation with enhanced gastric aqueous solubility and dissolution rate. Aqueous solubility can be enhanced by formulating solid dispersions (SDs) with a polyvinylpyrrolidone (PVP)-K30 hydrophilic carrier, using spray-drying technique. Aqueous and gastric pH dissolution can be achieved by macro-environmental pH modulation using sodium bicarbonate (NaHCO3) and magnesium hydroxide (Mg(OH)2) as the alkaline buffer. FLU/ESO-loaded SDs (FLU/ESO-SDs) significantly improved aqueous solubility of both drugs, compared to each drug powder. Dissolution studies in gastric pH and water were compared with the microenvironmental pH modulated formulations. The optimized FLU/ESO-SD powder formulation consisted of FLU/ESO/PVP-K30/sodium carbonate (Na2CO3) in a weight ratio 1:0.22:1.5:0.3, filled in the inner capsule. The outer capsule consisted of NaHCO3 and Mg(OH)2, which created the macro-environmental pH modulation. Increased aqueous and gastric pH dissolution of FLU and ESO from the SD was attributed to the alkaline buffer effects and most importantly, to drug transformation from crystalline to amorphous SD powder, clearly revealed by scanning electron microscopy, differential scanning calorimetry, and powder X-ray diffraction studies. Thus, the combined FLU and ESO SD powder can be effectively delivered as an immediate-release formulation using the macro-environmental pH modulation concept. Copyright © 2016. Published by Elsevier B.V.

  13. Optimization of the Büchi B-90 spray drying process using central composite design for preparation of solid dispersions.

    Science.gov (United States)

    Gu, Bing; Linehan, Brian; Tseng, Yin-Chao

    2015-08-01

    A central composite design approach was applied to study the effect of polymer concentration, inlet temperature and air flow rate on the spray drying process of the Büchi B-90 nano spray dryer (B-90). Hypromellose acetate succinate-LF was used for the Design of Experiment (DoE) study. Statistically significant models to predict the yield, spray rate, and drying efficiency were generated from the study. The spray drying conditions were optimized according to the models to maximize the yield and efficiency of the process. The models were further validated using a poorly water-soluble investigational compound (BI064) from Boehringer Ingelheim Pharmaceuticals. The polymer/drug ratio ranged from 1/1 to 3/1w/w. The spray dried formulations were amorphous determined by differential scanning calorimetry and X-ray powder diffraction. The particle size of the spray dried formulations was 2-10 μm under polarized light microscopy. All the formulations were physically stable for at least 3h when suspended in an aqueous vehicle composed of 1% methyl cellulose. This study demonstrates that DoE is a useful tool to optimize the spray drying process, and the B-90 can be used to efficiently produce amorphous solid dispersions with a limited quantity of drug substance available during drug discovery stages. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Humid storage conditions increase the dissolution rate of diazepam from solid dispersions prepared by melt agglomeration

    DEFF Research Database (Denmark)

    Jørgensen, Anna Cecilia; Torstenson, Anette Seo

    2008-01-01

    The purpose of this study is to investigate the effect of cooling mode and storage conditions on the dissolution rate of a solid dispersion prepared by melt agglomeration. The aim has been to relate this effect to the solid state properties of the agglomerates. The cooling mode had an effect on t...

  15. Importance of the Direct Contact of Amorphous Solid Particles with the Surface of Monolayers for the Transepithelial Permeation of Curcumin.

    Science.gov (United States)

    Kimura, Shunsuke; Kasatani, Sachiha; Tanaka, Megumi; Araki, Kaeko; Enomura, Masakazu; Moriyama, Kei; Inoue, Daisuke; Furubayashi, Tomoyuki; Tanaka, Akiko; Kusamori, Kosuke; Katsumi, Hidemasa; Sakane, Toshiyasu; Yamamoto, Akira

    2016-02-01

    The amorphization has been generally known to improve the absorption and permeation of poorly water-soluble drugs through the enhancement of the solubility. The present study focused on the direct contact of amorphous solid particles with the surface of the membrane using curcumin as a model for water-insoluble drugs. Amorphous nanoparticles of curcumin (ANC) were prepared with antisolvent crystallization method using a microreactor. The solubility of curcumin from ANC was two orders of magnitude higher than that of crystalline curcumin (CC). However, the permeation of curcumin from the saturated solution of ANC was negligible. The transepithelial permeation of curcumin from ANC suspension was significantly increased as compared to CC suspension, while the permeation was unlikely correlated with the solubility, and the increase in the permeation was dependent on the total concentration of curcumin in ANC suspension. The absorptive transport of curcumin (from apical to basal, A to B) from ANC suspension was much higher than the secretory transport (from basal to apical, B to A). In vitro transport of curcumin through air-interface monolayers is large from ANC but negligible from CC particles. These findings suggest that the direct contact of ANC with the absorptive membrane can play an important role in the transport of curcumin from ANC suspension. The results of the study suggest that amorphous particles may be directly involved in the transepithlial permeation of curcumin.

  16. An IR investigation of solid amorphous ethanol - Spectra, properties, and phase changes

    Science.gov (United States)

    Hudson, Reggie L.

    2017-12-01

    Mid- and far-infrared spectra of condensed ethanol (CH3CH2OH) at 10-160 K are presented, with a special focus on amorphous ethanol, the form of greatest astrochemical interest, and with special attention given to changes at 155-160 K. Infrared spectra of amorphous and crystalline forms are shown. The refractive index at 670 nm of amorphous ethanol at 16 K is reported, along with three IR band strengths and a density. A comparison is made to recent work on the isoelectronic compound ethanethiol (CH3CH2SH), and several astrochemical applications are suggested for future study.

  17. Multivariate Quantification of the Solid State Phase Composition of Co-Amorphous Naproxen-Indomethacin

    DEFF Research Database (Denmark)

    Beyer, Andreas; Grohganz, Holger; Löbmann, Korbinian

    2015-01-01

    To benefit from the optimized dissolution properties of active pharmaceutical ingredients in their amorphous forms, co-amorphisation as a viable tool to stabilize these amorphous phases is of both academic and industrial interest. Reports dealing with the physical stability and recrystallization...... components was prepared and analyzed by XRPD. In order to test the model performances, leave-one-out cross validation was performed and revealed root mean square errors of validation between 3.11% and 3.45% for the crystalline molar fractions and 5.57% for the co-amorphous molar fraction. In summary, even...

  18. Pressure-induced amorphization and reactivity of solid dimethyl acetylene probed by in situ FTIR and Raman spectroscopy

    Science.gov (United States)

    Guan, Jiwen; Daljeet, Roshan; Kieran, Arielle; Song, Yang

    2018-06-01

    Conjugated polymers are prominent semiconductors that have unique electric conductivity and photoluminescence. Synthesis of conjugated polymers under high pressure is extremely appealing because it does not require a catalyst or solvent used in conventional chemical methods. Transformation of acetylene and many of its derivatives to conjugated polymers using high pressure has been successfully achieved, but not with dimethyl acetylene (DMA). In this work, we present a high-pressure study on solid DMA using a diamond anvil cell up to 24.4 GPa at room temperature characterized by in situ Fourier transform infrared and Raman spectroscopy. Our results show that solid DMA exists in a phase II crystal structure and is stable up to 12 GPa. Above this pressure, amorphization was initiated and the process was completed at 24.4 GPa. The expected polymeric transformation was not evident upon compression, but only observed upon decompression from a threshold compression pressure (e.g. 14.4 GPa). In situ florescence measurements suggest excimer formation via crystal defects, which induces the chemical reactions. The vibrational spectral analysis suggests the products contain the amorphous poly(DMA) and possibly additional amorphous hydrogenated carbon material.

  19. Theory of amorphous ices.

    Science.gov (United States)

    Limmer, David T; Chandler, David

    2014-07-01

    We derive a phase diagram for amorphous solids and liquid supercooled water and explain why the amorphous solids of water exist in several different forms. Application of large-deviation theory allows us to prepare such phases in computer simulations. Along with nonequilibrium transitions between the ergodic liquid and two distinct amorphous solids, we establish coexistence between these two amorphous solids. The phase diagram we predict includes a nonequilibrium triple point where two amorphous phases and the liquid coexist. Whereas the amorphous solids are long-lived and slowly aging glasses, their melting can lead quickly to the formation of crystalline ice. Further, melting of the higher density amorphous solid at low pressures takes place in steps, transitioning to the lower-density glass before accessing a nonequilibrium liquid from which ice coarsens.

  20. Characterization of ZSM-5 zeolites synthesized by amorphous seed method by 29 Si solid state NMR

    International Nuclear Information System (INIS)

    Souza, Claudia M.G. de; Lau, Yiu Lam; Menezes, Sonia Cabral de

    1993-01-01

    The main objective of this analysis was to study the structure of samples synthesised by the amorphous seed method. The implications of this process upon the synthesized material were unknown. In the synthesis it was used ethanol and amorphous seed, which were added to the final synthesis mixture. It was observed a very significant reduction in the reaction time when compared to conventional synthesis. NMR was used to study the defects in the crystal lattice. Results are presented and discussed

  1. Curcumin-Eudragit® E PO solid dispersion: A simple and potent method to solve the problems of curcumin.

    Science.gov (United States)

    Li, Jinglei; Lee, Il Woo; Shin, Gye Hwa; Chen, Xiguang; Park, Hyun Jin

    2015-08-01

    Using a simple solution mixing method, curcumin was dispersed in the matrix of Eudragit® E PO polymer. Water solubility of curcumin in curcumin-Eudragit® E PO solid dispersion (Cur@EPO) was greatly increased. Based on the results of several tests, curcumin was demonstrated to exist in the polymer matrix in amorphous state. The interaction between curcumin and the polymer was investigated through Fourier transform infrared spectroscopy and (1)H NMR which implied that OH group of curcumin and carbonyl group of the polymer involved in the H bonding formation. Cur@EPO also provided protection function for curcumin as verified by the pH challenge and UV irradiation test. The pH value influenced curcumin release profile in which sustained release pattern was revealed. Additionally, in vitro transdermal test was conducted to assess the potential of Cur@EPO as a vehicle to deliver curcumin through this alternative administration route. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Enhanced dissolution and oral bioavailability of valsartan solid dispersions prepared by a freeze-drying technique using hydrophilic polymers.

    Science.gov (United States)

    Xu, Wei-Juan; Xie, Hong-Juan; Cao, Qing-Ri; Shi, Li-Li; Cao, Yue; Zhu, Xiao-Yin; Cui, Jing-Hao

    2016-01-01

    This study aimed to improve the dissolution rate and oral bioavailability of valsartan (VAL), a poorly soluble drug using solid dispersions (SDs). The SDs were prepared by a freeze-drying technique with polyethylene glycol 6000 (PEG6000) and hydroxypropylmethylcellulose (HPMC 100KV) as hydrophilic polymers, sodium hydroxide (NaOH) as an alkalizer, and poloxamer 188 as a surfactant without using any organic solvents. In vitro dissolution rate and physicochemical properties of the SDs were characterized using the USP paddle method, differential scanning calorimetry (DSC), X-ray diffractometry (XRD) and Fourier transform-infrared (FT-IR) spectroscopy, respectively. In addition, the oral bioavailability of SDs in rats was evaluated by using VAL (pure drug) as a reference. The dissolution rates of the SDs were significantly improved at pH 1.2 and pH 6.8 compared to those of the pure drug. The results from DSC, XRD showed that VAL was molecularly dispersed in the SDs as an amorphous form. The FT-IR results suggested that intermolecular hydrogen bonding had formed between VAL and its carriers. The SDs exhibited significantly higher values of AUC 0-24 h and Cmax in comparison with the pure drug. In conclusion, hydrophilic polymer-based SDs prepared by a freeze-drying technique can be a promising method to enhance dissolution rate and oral bioavailability of VAL.

  3. Investigation into mixing capability and solid dispersion preparation using the DSM Xplore Pharma Micro Extruder.

    Science.gov (United States)

    Sakai, Toshiro; Thommes, Markus

    2014-02-01

    The goal of this investigation was to qualify the DSM Xplore Pharma Micro Extruder as a formulation screening tool for early-stage hot-melt extrusion. Dispersive and distributive mixing was investigated using soluplus, copovidone or basic butylated methacrylate copolymer with sodium chloride (NaCl) in a batch size of 5 g. Eleven types of solid dispersions were prepared using various drugs and carriers in batches of 5 g in accordance with the literature. The dispersive mixing was a function of screw speed and recirculation time and the particle size was remarkably reduced after 1 min of processing, regardless of the polymers. An inverse relationship between the particle size and specific mechanical energy (SME) was also found. The SME values were higher than those in large-scale extruders. After 1 min recirculation at 200 rpm, the uniformity of NaCl content met the criteria of the European Pharmacopoeia, indicating that distributive mixing was achieved in this time. For the solid dispersions preparations, the results from different scanning calorimetry, powder X-ray diffractometry and in-vitro dissolution tests confirmed that all solid-dispersion systems were successfully prepared. These findings demonstrated that the extruder is a useful tool to screen solid-dispersion formulations and their material properties on a small scale. © 2013 Royal Pharmaceutical Society.

  4. Microparticles Containing Curcumin Solid Dispersion: Stability, Bioavailability and Anti-Inflammatory Activity.

    Science.gov (United States)

    Teixeira, C C C; Mendonça, L M; Bergamaschi, M M; Queiroz, R H C; Souza, G E P; Antunes, L M G; Freitas, L A P

    2016-04-01

    This work aimed at improving the solubility of curcumin by the preparation of spray-dried ternary solid dispersions containing Gelucire®50/13-Aerosil® and quantifying the resulting in vivo oral bioavailability and anti-inflammatory activity. The solid dispersion containing 40% of curcumin was characterised by calorimetry, infrared spectroscopy and X-ray powder diffraction. The solubility and dissolution rate of curcumin in aqueous HCl or phosphate buffer improved up to 3600- and 7.3-fold, respectively. Accelerated stability test demonstrated that the solid dispersion was stable for 9 months. The pharmacokinetic study showed a 5.5-fold increase in curcumin in rat blood plasma when compared to unprocessed curcumin. The solid dispersion also provided enhanced anti-inflammatory activity in rat paw oedema. Finally, the solid dispersion proposed here is a promising way to enhance curcumin bioavailability at an industrial pharmaceutical perspective, since its preparation applies the spray drying, which is an easy to scale up technique. The findings herein stimulate further in vivo evaluations and clinical tests as a cancer and Alzheimer chemoprevention agent.

  5. Development and characterization of solid dispersion of piroxicam for improvement of dissolution rate using hydrophilic carriers

    Directory of Open Access Journals (Sweden)

    Mohammad Barzegar-jalali

    2014-09-01

    Full Text Available Introduction: The main objective of this study was preparation and characterization of solid dispersion of piroxicam to enhance its dissolution rate. Methods: Solid dispersion formulations with different carriers including crospovidone, microcrystalline cellulose and Elaeagnus angustifolia fruit powder and with different drug: carrier ratios were prepared employing cogrinding method. Dissolution study of the piroxicam powders, physical mixtures and solid dispersions was performed in simulated gastric fluid and simulated intestinal fluid using USP Apparatus type II. The physical characterization of formulations were analyzed using powder X ray diffraction (PXRD, particle size analyzer and differential scanning calorimetry (DSC. Interactions between the drug and carriers were evaluated by Fourier transform infrared (FT-IR spectroscopic method. Results: It was revealed that all of three carriers increase the dissolution rate of piroxicam from physical mixtures and especially in solid dispersions compared to piroxicam pure and treated powders. PXRD and DSC results were confirmed the reduction of crystalline form of piroxicam. FT-IR analysis did not show any physicochemical interaction between drug and carriers in the solid dispersion formulations. Conclusion: Dissolution rate was dependent on the type and ratio of drug: carrier as well as pH of dissolution medium. Dissolution data of formulations were fitted well in to the linear Weibull as well as non-linear logistic and a suggested models.

  6. The effect of polymeric excipients on the physical properties and performance of amorphous dispersions: Part I, free volume and glass transition.

    Science.gov (United States)

    Li, Jinjiang; Zhao, Junshu; Tao, Li; Wang, Jennifer; Waknis, Vrushali; Pan, Duohai; Hubert, Mario; Raghavan, Krishnaswamy; Patel, Jatin

    2015-02-01

    To investigate the structural effect of polymeric excipients on the behavior of free volume of drug-polymer dispersions in relation to glass transition. Two drugs (indomethacin and ketoconazole) were selected to prepare amorphous dispersions with PVP, PVPVA, HPC, and HPMCAS through spray drying. The physical attributes of the dispersions were characterized using SEM and PXRD. The free volume (hole-size) of the dispersions along with drugs and polymers was measured using positron annihilation lifetime spectroscopy (PALS). Their glass transition temperatures (Tgs) were determined using DSC and DMA. FTIR spectra were recorded to identify hydrogen bonding in the dispersions. The chain structural difference-flexible (PVP and PVPVA) vs. inflexible (HPC and HPMCAS)-significantly impacts the free volume and Tgs of the dispersions as well as their deviation from ideality. Relative to Tg, free volume seems to be a better measure of hydrogen bonding interaction for the dispersions of PVP, HPC, and HPMCAS. The free volume of polymers and their dispersions in general appears to be related to their conformations in solution. Both the backbone chain rigidity of polymers as well as drug-polymer interaction can impact the free volume and glass transition behaviors of the dispersions.

  7. Transport Properties Of PbI2 Doped Silver Oxysalt Based Amorphous Solid Electrolytes

    Science.gov (United States)

    Shrisanjaykumar Jayswal, Manishkumar

    Solid electrolytes are a class of materials that conduct electricity by means of motion of ions like Ag+, Na+, Li +, Cu+, H+, F-, O -2 etc. in solid phase. The host materials include crystalline, polycrystalline, glasses, polymers and composites. Ion conducting glasses are one of the most sought after solid electrolytes that are useful in various electrochemical applications like solid state batteries, gas sensors, supercapacitors, electrochromic devices, to name a few. Since the discovery of fast silver ion transport in silver oxyhalide glasses at the end of the 1960s, many glasses showing large ionic conductivity up to 10-4 10-2 S/cm at room temperature have been developed, chiefly silver and copper ion conductors. The silver ion conducting glasses owe their high ionic conductivity mainly to stabilized alpha-AgI. AgI, as we know, undergoes a structural phase transition from wurtzite (beta phase) at room temperature to body centered cubic (alpha phase) structure at temperatures higher than 146 °C. The alpha-AgI possesses approximately six order of higher ionic conductivity than beta-AgI. The high ionic conductivity of alpha-AgI is attributed to its molten sublattice type of structure, which facilitates easy Ag+ ion migration, like a liquid. And hence, several attempts have been made to stabilize it at room temperature in crystalline as well as non-crystalline hosts like oxide and non-oxide glasses. Recently, in order to stabilize AgI in glasses, instead of directly doping it, indirect routes have also been explored. Where, a metal iodide salt along with silver oxide or silver phosphate is taken and an exchange reaction permitted by Hard and Soft, Acid and Base (HSAB) principle occurs between the two and AgI and metal oxide form in the glass forming melt. Work done in the present thesis has been organized in seven chapters as follows: Chapter 1: A review and background information of different solid electrolyte materials and their development is presented. Along

  8. Diffusion and Clustering of Carbon Dioxide on Non-porous Amorphous Solid Water

    Energy Technology Data Exchange (ETDEWEB)

    He, Jiao; Emtiaz, Shahnewaj M.; Vidali, Gianfranco, E-mail: jhe08@syr.edu, E-mail: gvidali@syr.edu [Physics Department, Syracuse University, Syracuse, NY 13244 (United States)

    2017-03-01

    Observations by ISO and Spitzer toward young stellar objects showed that CO{sub 2} segregates in the icy mantles covering dust grains. Thermal processing of the ice mixture was proposed as being responsible for the segregation. Although several laboratories studied thermally induced segregation, a satisfying quantification is still missing. We propose that the diffusion of CO{sub 2} along pores inside water ice is the key to quantify segregation. We combined Temperature Programmed Desorption and Reflection Absorption InfraRed Spectroscopy to study how CO{sub 2} molecules interact on a non-porous amorphous solid water (np-ASW) surface. We found that CO{sub 2} diffuses significantly on an np-ASW surface above 65 K and clusters are formed at well below one monolayer. A simple rate equation simulation finds that the diffusion energy barrier of CO{sub 2} on np-ASW is 2150 ± 50 K, assuming a diffusion pre-exponential factor of 10{sup 12} s{sup −1}. This energy should also apply to the diffusion of CO{sub 2} on the wall of pores. The binding energy of CO{sub 2} from CO{sub 2} clusters and CO{sub 2} from H{sub 2}O ice has been found to be 2415 ± 20 K and 2250 ± 20 K, respectively, assuming the same prefactor for desorption. CO{sub 2}–CO{sub 2} interaction is stronger than CO{sub 2}–H{sub 2}O interaction, in agreement with the experimental finding that CO{sub 2} does not wet the np-ASW surface. For comparison, we carried out similar experiments with CO on np-ASW, and found that the CO–CO interaction is always weaker than CO–H{sub 2}O. As a result, CO wets the np-ASW surface. This study should be of help to uncover the thermal history of CO{sub 2} on the icy mantles of dust grains.

  9. Carbon-free Solid Dispersion LiCoO2 Redox Couple Characterization and Electrochemical Evaluation for All Solid Dispersion Redox Flow Batteries

    International Nuclear Information System (INIS)

    Qi, Zhaoxiang; Liu, Aaron L.; Koenig, Gary M.

    2017-01-01

    Highlights: • LiCoO 2 particles can be cycled in carbon-free and binder-free coin cells. • A carbon-free LiCoO 2 suspension is electrochemically oxidized and reduced. • Comparable size LiCoO 2 and Li 4 Ti 5 O 12 suspensions have similar rheological properties. • First demonstration of redox couples with solid suspensions for both electrodes. - Abstract: Semi-solid flow batteries have been reported to have among the highest energy densities for redox flow batteries, however, they rely on percolated carbon networks which increase the electrolyte viscosity significantly. We report the first demonstration of carbon-free redox flow couples comprised of dispersed lithium-ion battery active material suspensions, with sub-micrometer LiCoO 2 (LCO) particles at the cathode and Li 4 Ti 5 O 12 (LTO) particles at the anode. Both electrochemical and rheological properties of the LCO suspensions are reported and compared to previous reports for LTO dispersed electrochemical redox couples. An LTO anode and LCO cathode full cell was constructed and reversible electrochemical redox reaction of the dispersed particles was successfully demonstrated. This carbon-free dispersed lithium-ion active material full cell provides a proof-of-concept for a system that lies between the relatively high viscosity semi-solid flow cells with percolated carbon networks and the relatively low energy density conventional flow cells comprised of dissolved transition metals, providing a system for future study of the trade-off between energy density and viscosity for electrochemical flow cells that rely on solid active materials.

  10. Solid-state amorphization of SmFe{sub 3} by hydrogenation

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, K.H.; Kubis, M.; Handstein, A.; Gutfleisch, O.

    2000-05-10

    Hydrogen-induced amorphization (HIA) has received much attention as a method for the preparation of amorphous compounds since its discovery by Yeh et al. Meanwhile it has been observed for a large number of intermetallic compounds with C15, C23, B8{sub 2}, DO{sub 19} and L1{sub 2} structures. E.G. the C15 Laves-type compounds (MgCu{sub 2}-type structure) of rare earth (R) - transition metal (T) compounds RT{sub 2} show HIA for R = Y, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho and Er. Aoki et al. postulated that new amorphizing compounds can be expected at high hydrogen pressures. In this work, the structural changes of SmFe{sub 3} (PuNi{sub 3}-type structure) during heating in high hydrogen pressures are reported.

  11. Solid-state amorphization of SmFe3 by hydrogenation

    International Nuclear Information System (INIS)

    Mueller, K.H.; Kubis, M.; Handstein, A.; Gutfleisch, O.

    2000-01-01

    Hydrogen-induced amorphization (HIA) has received much attention as a method for the preparation of amorphous compounds since its discovery by Yeh et al. Meanwhile it has been observed for a large number of intermetallic compounds with C15, C23, B8 2 , DO 19 and L1 2 structures. E.G. the C15 Laves-type compounds (MgCu 2 -type structure) of rare earth (R) - transition metal (T) compounds RT 2 show HIA for R = Y, Ce, Pr, Nd, Sm, Gd, Tb, Dy, Ho and Er. Aoki et al. postulated that new amorphizing compounds can be expected at high hydrogen pressures. In this work, the structural changes of SmFe 3 (PuNi 3 -type structure) during heating in high hydrogen pressures are reported

  12. On the structure of amorphous calcium carbonate--a detailed study by solid-state NMR spectroscopy.

    Science.gov (United States)

    Nebel, Holger; Neumann, Markus; Mayer, Christian; Epple, Matthias

    2008-09-01

    The calcium carbonate phases calcite, aragonite, vaterite, monohydrocalcite (calcium carbonate monohydrate), and ikaite (calcium carbonate hexahydrate) were studied by solid-state NMR spectroscopy ( (1)H and (13)C). Further model compounds were sodium hydrogencarbonate, potassium hydrogencarbonate, and calcium hydroxide. With the help of these data, the structure of synthetically prepared additive-free amorphous calcium carbonate (ACC) was analyzed. ACC contains molecular water (as H 2O), a small amount of mobile hydroxide, and no hydrogencarbonate. This supports the concept of ACC as a transient precursor in the formation of calcium carbonate biominerals.

  13. Short-range correlations control the G/K and Poisson ratios of amorphous solids and metallic glasses

    Energy Technology Data Exchange (ETDEWEB)

    Zaccone, Alessio; Terentjev, Eugene M. [Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom)

    2014-01-21

    The bulk modulus of many amorphous materials, such as metallic glasses, behaves nearly in agreement with the assumption of affine deformation, namely that the atoms are displaced just by the amount prescribed by the applied strain. In contrast, the shear modulus behaves as for nonaffine deformations, with additional displacements due to the structural disorder which induce a marked material softening to shear. The consequence is an anomalously large ratio of the bulk modulus to the shear modulus for disordered materials characterized by dense atomic packing, but not for random networks with point atoms. We explain this phenomenon with a microscopic derivation of the elastic moduli of amorphous solids accounting for the interplay of nonaffinity and short-range particle correlations due to excluded volume. Short-range order is responsible for a reduction of the nonaffinity which is much stronger under compression, where the geometric coupling between nonaffinity and the deformation field is strong, whilst under shear this coupling is weak. Predictions of the Poisson ratio based on this model allow us to rationalize the trends as a function of coordination and atomic packing observed with many amorphous materials.

  14. The significance of the amorphous potential energy landscape for dictating glassy dynamics and driving solid-state crystallisation.

    Science.gov (United States)

    Ruggiero, Michael T; Krynski, Marcin; Kissi, Eric Ofosu; Sibik, Juraj; Markl, Daniel; Tan, Nicholas Y; Arslanov, Denis; van der Zande, Wim; Redlich, Britta; Korter, Timothy M; Grohganz, Holger; Löbmann, Korbinian; Rades, Thomas; Elliott, Stephen R; Zeitler, J Axel

    2017-11-15

    The fundamental origins surrounding the dynamics of disordered solids near their characteristic glass transitions continue to be fiercely debated, even though a vast number of materials can form amorphous solids, including small-molecule organic, inorganic, covalent, metallic, and even large biological systems. The glass-transition temperature, T g , can be readily detected by a diverse set of techniques, but given that these measurement modalities probe vastly different processes, there has been significant debate regarding the question of why T g can be detected across all of them. Here we show clear experimental and computational evidence in support of a theory that proposes that the shape and structure of the potential-energy surface (PES) is the fundamental factor underlying the glass-transition processes, regardless of the frequency that experimental methods probe. Whilst this has been proposed previously, we demonstrate, using ab initio molecular-dynamics (AIMD) simulations, that it is of critical importance to carefully consider the complete PES - both the intra-molecular and inter-molecular features - in order to fully understand the entire range of atomic-dynamical processes in disordered solids. Finally, we show that it is possible to utilise this dependence to directly manipulate and harness amorphous dynamics in order to control the behaviour of such solids by using high-powered terahertz pulses to induce crystallisation and preferential crystal-polymorph growth in glasses. Combined, these findings provide compelling evidence that the PES landscape, and the corresponding energy barriers, are the ultimate controlling feature behind the atomic and molecular dynamics of disordered solids, regardless of the frequency at which they occur.

  15. Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan.

    Science.gov (United States)

    Lee, Jae-Young; Kang, Wie-Soo; Piao, Jingpei; Yoon, In-Soo; Kim, Dae-Duk; Cho, Hyun-Jong

    2015-01-01

    Soluplus(®) (SP) and D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based solid dispersion (SD) formulations were developed by hot-melt extrusion (HME) to improve oral bioavailability of valsartan (VST). HME process with twin-screw configuration for generating a high shear stress was used to prepare VST SD formulations. The thermodynamic state of the drug and its dispersion in the polymers were evaluated by solid-state studies, including Fourier-transform infrared, X-ray diffraction, and differential scanning calorimetry. Drug release from the SD formulations was assessed at pH values of 1.2, 4.0, and 6.8. Pharmacokinetic study was performed in rats to estimate the oral absorption of VST. HME with a high shear rate produced by the twin-screw system was successfully applied to prepare VST-loaded SD formulations. Drug amorphization and its molecular dispersion in the polymer matrix were verified by several solid-state studies. Drug release from SD formulations was improved, compared to the pure drug, particularly at pH 6.8. Oral absorption of drug in rats was also enhanced in SP and TPGS-based SD groups compared to that in the pure drug group. SP and TPGS-based SDs, prepared by the HME process, could be used to improve aqueous solubility, dissolution, and oral absorption of poorly water-soluble drugs.

  16. Structures of the particles of the condensed dispersed phase in solid fuel combustion products plasma

    International Nuclear Information System (INIS)

    Samaryan, A.A.; Chernyshev, A.V.; Nefedov, A.P.; Petrov, O.F.; Fortov, V.E.; Mikhailov, Yu.M.; Mintsev, V.B.

    2000-01-01

    The results of experimental investigations of a type of dusty plasma which has been least studied--the plasma of solid fuel combustion products--were presented. Experiments to determine the parameters of the plasma of the combustion products of synthetic solid fuels with various compositions together with simultaneous diagnostics of the degree of ordering of the structures of the particles of the dispersed condensed phase were performed. The measurements showed that the charge composition of the plasma of the solid fuels combustion products depends strongly on the easily ionized alkali-metal impurities which are always present in synthetic fuel in one or another amount. An ordered arrangement of the particles of a condensed dispersed phase in structures that form in a boundary region between the high-temperature and condensation zones was observed for samples of aluminum-coated solid fuels with a low content of alkali-metal impurities

  17. Amorphous chalcogenide semiconductors for solid state dosimetric systems of high-energetic ionizing radiation

    International Nuclear Information System (INIS)

    Shpotyuk, O.

    1997-01-01

    The application possibilities of amorphous chalcogenide semiconductors use as radiation-sensitive elements of high-energetic (E > 1 MeV) dosimetric systems are analysed. It is shown that investigated materials are characterized by more wide region of registered absorbed doses and low temperature threshold of radiation information bleaching in comparison with well-known analogies based on coloring oxide glasses. (author)

  18. Novel family of solid acid catalysts: substantially amorphous or partially crystalline zeolitic materials

    CSIR Research Space (South Africa)

    Nicolaides, CP

    1999-01-01

    Full Text Available of the samples obtained at the various temperatures showed that for synthesis temperatures of up to 70 degrees C, X-ray amorphous aluminosilicates were obtained, whereas treatment at 90 degrees C produced a material exhibiting a 2% XRD crystallinity. Higher...

  19. γ-radiation resistance of amorphous films of a-Si1-xGex:H solid solution

    International Nuclear Information System (INIS)

    Najafov, B.A.; Isakov, G.I.; Figarov, V.R.

    2004-01-01

    Full text: a-Si 1-x Ge x :H solid solution amorphous films (with x=0.4; 0.7, H=17 at. %) were fabricated by the plasma-chemical deposition method 1 μm thick, at the substrate temperature of 200 deg. C, the rate of deposition was 0.1 A /s, and the distance between the target and the substrate was L∼25 cm. The dispersion process was conducted in a hydrogenous plasma medium, that had been obtained with the use of a magnetron and a RF field. Taken ESR spectra of a-Si 1-x Ge x :H at 80 K were asymmetric in form, inasmuch as they were composed of two kinds relating to free bonds of Si and Ge, respectively. At the same time the observed signal was not a simple superposition of the two signals (for Si and for Ge), since they violently interacted with each other and the resulting signal in the intervening interval aimed to assume the form of a sole line. Because of this the observed spectrum on the left and on the right could be depicted by a superposition of the two signal: with g-factor of g=2.004-2.006 and the line width of 51-65 G and with g=2.018-2.022 and 73-86 G relating to the silicon and germanium free bonds, respectively. In this way it could be evaluated densities of Si and Ge free bonds, taken separately. But in accordance with computation of molecular orbitals in a-Si 1-x Ge x :H, the presence of atoms, adjacent to the orbitals, almost does not alter g-value of ESR-signals from both Si and Ge free bonds. By the IR absorption spectrum determining a number of Si-H bonds, and also a number of Ge-H bonds, it may assert that a number of Ge free bonds is 8-10 times larger than that of Si. It is proved that in a-Si 1 x Ge x : H films H atoms are mainly bound to Si atoms and so a total number of H is reduced with increasing of Ge content. That stands for the density of Ge free bonds decreases a number of H atoms, bound to Ge, but it does not a number of H atoms, bound to Si. This fact is also confirmed by ESR investigations. ESR investigations in a-Si 1-x Ge x :H

  20. Formation of the prebiotic molecule NH2CHO on astronomical amorphous solid water surfaces: accurate tunneling rate calculations.

    Science.gov (United States)

    Song, Lei; Kästner, Johannes

    2016-10-26

    Investigating how formamide forms in the interstellar medium is a hot topic in astrochemistry, which can contribute to our understanding of the origin of life on Earth. We have constructed a QM/MM model to simulate the hydrogenation of isocyanic acid on amorphous solid water surfaces to form formamide. The binding energy of HNCO on the ASW surface varies significantly between different binding sites, we found values between ∼0 and 100 kJ mol -1 . The barrier for the hydrogenation reaction is almost independent of the binding energy, though. We calculated tunneling rate constants of H + HNCO → NH 2 CO at temperatures down to 103 K combining QM/MM with instanton theory. Tunneling dominates the reaction at such low temperatures. The tunneling reaction is hardly accelerated by the amorphous solid water surface compared to the gas phase for this system, even though the activation energy of the surface reaction is lower than the one of the gas-phase reaction. Both the height and width of the barrier affect the tunneling rate in practice. Strong kinetic isotope effects were observed by comparing to rate constants of D + HNCO → NHDCO. At 103 K we found a KIE of 231 on the surface and 146 in the gas phase. Furthermore, we investigated the gas-phase reaction NH 2 + H 2 CO → NH 2 CHO + H and found it unlikely to occur at cryogenic temperatures. The data of our tunneling rate constants are expected to significantly influence astrochemical models.

  1. Fabrication and evaluation of pH-modulated solid dispersion for telmisartan by spray-drying technique.

    Science.gov (United States)

    Marasini, Nirmal; Tran, Tuan Hiep; Poudel, Bijay Kumar; Cho, Hyuk Jun; Choi, Young Keun; Chi, Sang-Cheol; Choi, Han-Gon; Yong, Chul Soon; Kim, Jong Oh

    2013-01-30

    The present study was undertaken to overcome the problems associated with solubility, dissolution and oral bioavailability of a poorly water-soluble ionizable drug, telmisartan (TMS). For these purposes, a solubility test was carried to select the appropriate formulation composition from various carriers and alkalizers. Solid dispersions (SDs) of TMS were prepared at different drug-to-carrier ratios by the spray-drying technique, and were characterized by dissolution and aqueous solubility studies. The optimum formulation was investigated by dissolution studies at different pH and water media and its solid state characterisations were performed by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction (XRD) studies. In solubility and dissolution tests, all TMS-loaded pH-modulated SDs (pH(M)-SDs) exhibited marked improvement in the dissolution behavior when compared with crystalline TMS powder. The optimum formulation of pH(M)-SD consisted of TMS/PVP (polyvinylpyrrolidone) K30/Na(2)CO(3) at a weight ratio of 2/0.5/3 and showed significant improvement in the aqueous solubility and dissolution rate by approximately 40,000- and 3-fold, respectively, compared to TMS powder. Solid-state characterization revealed the changed in crystallinity of TMS into amorphous state. Furthermore, area under the drug concentration time-curve (AUC) of TMS from the pH(M)-SD increased by 13.4- and 2.1-fold, compared with TMS powder and commercial product, respectively. According to these observations, taken together with dissolution and pharmacokinetic behaviors, pH-modulated SD in the presence of an alkalizer for a poorly water-soluble ionizable drug, TMS, appeared to be efficacious for enhancing its bioavailability. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Dispersive solid-phase imprinting of proteins for the production of plastic antibodies

    DEFF Research Database (Denmark)

    Ashley, Jon; Feng, Xiaotong; Halder, Arnab

    2018-01-01

    We describe a novel dispersive solid-phase imprinting technique for the production of nano-sized molecularly imprinted polymers (nanoMIPs) as plastic antibodies. The template was immobilized on in-house synthesized magnetic microspheres instead of conventional glass beads. As a result, high...

  3. The mechanisms of drug release from solid dispersions in water-soluble polymers.

    Science.gov (United States)

    Craig, Duncan Q M

    2002-01-14

    Solid dispersions in water-soluble carriers have attracted considerable interest as a means of improving the dissolution rate, and hence possibly bioavailability, of a range of hydrophobic drugs. However, despite the publication of numerous original papers and reviews on the subject, the mechanisms underpinning the observed improvements in dissolution rate are not yet understood. In this review the current consensus with regard to the solid-state structure and dissolution properties of solid dispersions is critically assessed. In particular the theories of carrier- and drug-controlled dissolution are highlighted. A model is proposed whereby the release behaviour from the dispersions may be understood in terms of the dissolution or otherwise of the drug into the concentrated aqueous polymer layer adjacent to the solid surface, including a derivation of an expression to describe the release of intact particles from the dispersions. The implications of a deeper understanding of the dissolution mechanisms are discussed, with particular emphasis on optimising the choice of carrier and manufacturing method and the prediction of stability problems.

  4. CLSM as quantitative method to determine the size of drug crystals in a solid dispersion

    NARCIS (Netherlands)

    de Waard, Hans; Hessels, Martin J T; Boon, Maarten; Sjollema, Klaas A; Hinrichs, Wouter L J; Eissens, Anko C; Frijlink, Henderik W

    2011-01-01

    PURPOSE: To test whether confocal laser scanning microscopy (CLSM) can be used as an analytical tool to determine the drug crystal size in a powder mixture or a crystalline solid dispersion. METHODS: Crystals of the autofluorescent drug dipyridamole were incorporated in a matrix of crystalline

  5. Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tablets

    NARCIS (Netherlands)

    Srinarong, Parinda; Kouwen, Sander; Visser, Marinella R; Hinrichs, Wouter L J; Frijlink, Henderik W

    2010-01-01

    The objective of this study was to compare the dissolution behavior of tablets prepared from solid dispersions with and without drug-carrier interactions. Diazepam and nifedipine were used as model drugs. Two types of carriers were used; polyvinylpyrrolidone (PVP K12, K30 and K60) and saccharides

  6. Solid dispersions in oncology: a solution to solubility-limited oral drug absorption

    NARCIS (Netherlands)

    Sawicki, Emilia

    2017-01-01

    This thesis discusses the formulation method solid dispersion and how it works to resolve solubility-limited absorption of orally dosed anticancer drugs. Dissolution in water is essential for drug absorption because only dissolved drug molecules are absorbed. The problem is that half of the arsenal

  7. Development and evaluation of alginate-chitosan gastric floating beads loading with oxymatrine solid dispersion.

    Science.gov (United States)

    Liu, Yanhua; Chen, Lihong; Zhou, Chengming; Yang, Jianhong; Hou, Yanhui; Wang, Wenping

    2016-01-01

    Oxymatrine (OM) can be metabolized to matrine in gastrointestinal ileocecal valve after oral administration, which affects pharmacological activity and reduce bioavailability of OM. A type of multiple-unit alginate-chitosan (Alg-Cs) floating beads was prepared by the ionotropic gelation method for gastroretention delivery of OM. A solid dispersion technique was applied and incorporated into beads to enhance the OM encapsulation efficiency (EE) and sustain the drug release. The surface morphology and internal hollow structure of beads were evaluated using optical microscopy and scanning electron microscopy (SEM). The developed Alg-Cs beads were spherical in shape with hollow internal structure and had particle size of 3.49 ± 0.09 mm and 1.33 ± 0.09 mm for wet and dried beads. Over 84% of the optimized OM solid dispersion-loaded Alg-Cs beads were able to continuously float over the simulated gastric fluid for 12 h in vitro. The OM solid dispersion-loaded Alg-Cs beads showed drug EE of 67.07%, which was much higher than that of beads loading with pure OM. Compared with the immediate release of OM capsules and pure OM-loaded beads, the release of OM from solid dispersion-loaded Alg-Cs beads was in a sustained-release manner for 12 h. Prolonged gastric retention time of over 8.5 h was achieved for OM solid dispersion-loaded Alg-Cs floating beads in healthy rabbit in in vivo floating ability evaluated by X-ray imaging. The developed Alg-Cs beads loading with OM solid dispersion displayed excellent performance features characterized by excellent gastric floating ability, high drug EE and sustained-release pattern. The study illustrated the potential use of Alg-Cs floating beads combined with the solid dispersion technique for prolonging gastric retention and sustaining release of OM, which could provide a promising drug delivery system for gastric-specific delivery of OM for bioavailability enhancement.

  8. Recent advances in co-amorphous drug formulations

    DEFF Research Database (Denmark)

    Dengale, Swapnil Jayant; Grohganz, Holger; Rades, Thomas

    2016-01-01

    with other amorphous stabilization techniques. Because of this, several research groups started to investigate the co-amorphous formulation approach, resulting in an increasing amount of scientific publications over the last few years. This study provides an overview of the co-amorphous field and its recent......Co-amorphous drug delivery systems have recently gained considerable interest in the pharmaceutical field because of their potential to improve oral bioavailability of poorly water-soluble drugs through drug dissolution enhancement as a result of the amorphous nature of the material. A co...... findings. In particular, we investigate co-amorphous formulations from the viewpoint of solid dispersions, describe their formation and mechanism of stabilization, study their impact on dissolution and in vivo performance and briefly outline the future potentials....

  9. Amorphous chalcogenide semiconductors for solid state dosimetric systems of high-energetic ionizing radiation

    Energy Technology Data Exchange (ETDEWEB)

    Shpotyuk, O. [Pedagogical University, Czestochowa (Poland)]|[Institute of Materials, Lvov (Ukraine)

    1997-12-31

    The application possibilities of amorphous chalcogenide semiconductors use as radiation-sensitive elements of high-energetic (E > 1 MeV) dosimetric systems are analysed. It is shown that investigated materials are characterized by more wide region of registered absorbed doses and low temperature threshold of radiation information bleaching in comparison with well-known analogies based on coloring oxide glasses. (author). 16 refs, 1 tab.

  10. Synthesis and electrochemical evaluation of an amorphous titanium dioxide derived from a solid state precursor

    Science.gov (United States)

    Joyce, Christopher D.; McIntyre, Toni; Simmons, Sade; LaDuca, Holly; Breitzer, Jonathan G.; Lopez, Carmen M.; Jansen, Andrew N.; Vaughey, J. T.

    Titanium oxides are an important class of lithium-ion battery electrodes owing to their good capacity and stability within the cell environment. Although most Ti(IV) oxides are poor electronic conductors, new methods developed to synthesize nanometer scale primary particles have achieved the higher rate capability needed for modern commercial applications. In this report, the anionic water stable titanium oxalate anion [TiO(C 2O 4) 2] 2- was isolated in high yield as the insoluble DABCO (1,4-diazabicyclo[2.2.2]octane) salt. Powder X-ray diffraction studies show that the titanium dioxide material isolated after annealing in air is initially amorphous, converts to N-doped anatase above 400 °C, then to rutile above 600 °C. Electrochemical studies indicate that the amorphous titanium dioxide phase within a carbon matrix has a stable cycling capacity of ∼350 mAh g -1. On crystallizing at 400 °C to a carbon-coated anatase the capacity drops to 210 mAh g -1, and finally upon carbon burn-off to 50 mAh g -1. Mixtures of the amorphous titanium dioxide and Li 4Ti 5O 12 showed a similar electrochemical profile and capacity to Li 4Ti 5O 12 but with the addition of a sloping region to the end of the discharge curve that could be advantageous for determining state-of-charge in systems using Li 4Ti 5O 12.

  11. Development of megestrol acetate solid dispersion nanoparticles for enhanced oral delivery by using a supercritical antisolvent process.

    Science.gov (United States)

    Ha, Eun-Sol; Kim, Jeong-Soo; Baek, In-Hwan; Yoo, Jin-Wook; Jung, Yunjin; Moon, Hyung Ryong; Kim, Min-Soo

    2015-01-01

    In the present study, solid dispersion nanoparticles with a hydrophilic polymer and surfactant were developed using the supercritical antisolvent (SAS) process to improve the dissolution and oral absorption of megestrol acetate. The physicochemical properties of the megestrol acetate solid dispersion nanoparticles were characterized using scanning electron microscopy, differential scanning calorimetry, powder X-ray diffraction, and a particle-size analyzer. The dissolution and oral bioavailability of the nanoparticles were also evaluated in rats. The mean particle size of all solid dispersion nanoparticles that were prepared was nanoparticles. Hydroxypropylmethyl cellulose (HPMC) solid dispersion nanoparticles significantly increased the maximum dissolution when compared with polyvinylpyrrolidone K30 solid dispersion nanoparticles. The extent and rate of dissolution of megestrol acetate increased after the addition of a surfactant into the HPMC solid dispersion nanoparticles. The most effective surfactant was Ryoto sugar ester L1695, followed by D-α-tocopheryl polyethylene glycol 1000 succinate. In this study, the solid dispersion nanoparticles with a drug:HPMC:Ryoto sugar ester L1695 ratio of 1:2:1 showed >95% rapid dissolution within 30 minutes, in addition to good oral bioavailability, with approximately 4.0- and 5.5-fold higher area under the curve (0-24 hours) and maximum concentration, respectively, than raw megestrol acetate powder. These results suggest that the preparation of megestrol acetate solid dispersion nanoparticles using the supercritical antisolvent process is a promising approach to improve the dissolution and absorption properties of megestrol acetate.

  12. Electrospun 4th-Generation Solid Dispersions of Poorly Water-Soluble Drug Utilizing Two Different Processes

    Directory of Open Access Journals (Sweden)

    Zhu Zhang

    2018-01-01

    Full Text Available Different from traditional solid dispersion (SD for improving the dissolution rates of poorly water-soluble drugs, the upgraded 4th SD was developed to furnish a drug sustained-release profile. In this work, two different kinds of 4th SDs were fabricated using two electrospinning processes. One is a ternary SD (nanofibers F2 that consisted of ethyl cellulose (EC, polyethylene glycol 1000 (PEG, and tamoxifen citrate (TAM from a modified coaxial process, and the other is a binary SD (nanofibers F1 which is comprised of EC and TAM from a single-fluid blending process. Scanning electronic microscopic observations demonstrated that F2 (330±50 nm showed a better quality than F1 (870±230 nm in terms of size and size distribution although both of them had a smooth surface morphology and a cross section. X-ray diffraction patterns verified that both SDs were amorphous nanocomposites owing to the favorable secondary interactions among these components, as suggested from the results of FTIR. In vitro dissolution experiments indicated that F2 could furnish an improved drug sustained-release characteristics compared to F1, exhausting all the contained TAM and having weaker leveling-off late release. The molecular behaviors of drug sustained-release from the binary 4th SD were suggested. The protocols reported here paved an alternative way for developing novel functional nanomaterials for effective delivery of poorly water-soluble drugs.

  13. Electrosprayed core–shell solid dispersions of acyclovir fabricated using an epoxy-coated concentric spray head

    Science.gov (United States)

    Liu, Zhe-Peng; Cui, Lei; Yu, Deng-Guang; Zhao, Zhuan-Xia; Chen, Lan

    2014-01-01

    A novel structural solid dispersion (SD) taking the form of core–shell microparticles for poorly water-soluble drugs is reported for the first time. Using polyvinylpyrrolidone (PVP) as a hydrophilic polymer matrix, the SDs were fabricated using coaxial electrospraying (characterized by an epoxy-coated concentric spray head), although the core fluids were unprocessable using one-fluid electrospraying. Through manipulating the flow rates of the core drug-loaded solutions, two types of core–shell microparticles with tunable drug contents were prepared. They had average diameters of 1.36±0.67 and 1.74±0.58 μm, and were essentially a combination of nanocomposites with the active ingredient acyclovir (ACY) distributed in the inner core, and the sweeter sucralose and transmembrane enhancer sodium dodecyl sulfate localized in the outer shell. Differential scanning calorimetry and X-ray diffraction results demonstrated that ACY, sodium dodecyl sulfate, and sucralose were well distributed in the PVP matrix in an amorphous state because of favorable second-order interactions. In vitro dissolution and permeation studies showed that the core–shell microparticle SDs rapidly freed ACY within 1 minute and promoted nearly eightfold increases in permeation rate across the sublingual mucosa compared with raw ACY powders. PMID:24790437

  14. Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability.

    Science.gov (United States)

    Parikh, Ankit; Kathawala, Krishna; Song, Yunmei; Zhou, Xin-Fu; Garg, Sanjay

    2018-05-29

    Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.

  15. Solid lipid dispersions: potential delivery system for functional ingredients in foods.

    Science.gov (United States)

    Asumadu-Mensah, Aboagyewa; Smith, Kevin W; Ribeiro, Henelyta S

    2013-07-01

    Structured solid lipid (SL) systems have the advantages of long-term physical stability, low surfactant concentrations, and may exhibit controlled release of active ingredients. In this research work, the potential use of high-melting SLs for the production of the above structured SL carrier systems was investigated. Dispersions containing either SL or blend of solid lipid and oil (SL+O) were produced by a hot melt high-pressure homogenization method. Experiments involved the use of 3 different SLs for the disperse phase: stearic acid, candelilla wax and carnauba wax. Sunflower oil was incorporated in the disperse phase for the production of the dispersions containing lipid and oil. In order to evaluate the practical aspects of structured particles, analytical techniques were used including: static light scattering to measure particle sizes, transmission electron microscopy (TEM) for investigating particle morphology and differential scanning calorimetry (DSC) to investigate the crystallization behavior of lipids in bulk and in dispersions. Results showed different mean particle sizes depending on the type of lipid used in the disperse phase. Particle sizes for the 3 lipids were: stearic acid (SL: 195 ± 2.5 nm; SL+O: 138 ± 6.0 nm); candelilla wax (SL: 178 ± 1.7 nm; SL+O: 144 ± 0.6 nm); carnauba wax (SL: 303 ± 1.5 nm; SL+O: 295 ± 5.0 nm). TEM results gave an insight into the practical morphology, showing plate-like and needle-like structures. DSC investigations also revealed that SL dispersions melted and crystallized at lower temperatures than the bulk. This decrease can be explained by the small particle sizes of the dispersion, the high-specific surface area, and the presence of a surfactant. © 2013 Institute of Food Technologists®

  16. CONDENSED MATTER: STRUCTURE, MECHANICAL AND THERMAL PROPERTIES: Molecular Dynamics Study of Stability of Solid Solutions and Amorphous Phase in the Cu-Al System

    Science.gov (United States)

    Yang, Bin; Lai, Wen-Sheng

    2009-06-01

    The relative stability of fcc and bcc solid solutions and amorphous phase with different compositions in the Cu-Al system is studied by molecular dynamics simulations with n-body potentials. For Cu1-xAlx alloys, the calculations show that the fcc solid solution has the lowest energies in the composition region with x 0.72, while the bee solid solution has the lowest energies in the central composition range, in agreement with the ball-milling experiments that a single bcc solid solution with 0.30 < x < 0.70 is obtained. The evolution of structures in solid solutions and amorphous phase is studied by the coordination number (CN) and bond-length analysis so as to unveil the underlying physics. It is found that the energy sequence among three phases is determined by the competition in energy change originating from the bond length and CNs (or the number of bonds).

  17. Enhanced dissolution rate of dronedarone hydrochloride via preparation of solid dispersion using vinylpyrrolidone-vinyl acetate copolymer (Kollidone® VA 64)

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hyuck Jun; Kang, Myung Joo [College of Pharmacy, Dankook University, Cheonan (Korea, Republic of); Han, Sang Duk [Dong-A ST Rese arch Institute, Pharmaceutical Product Research Laboratories, Yongin (Korea, Republic of)

    2015-09-15

    Solid dispersion (SD) systems have been widely used to increase the dissolution rate and oral absorption of poorly water-soluble compounds. In order to enhance the dissolution rate of dronedarone hydrochloride (DRN), a recent antiarrhythmic agent, SDs of DRN were formulated using conventional solvent evaporation method with amorphous polymers including hydroxypropyl methyl cellulose (HPMC), poly(vinyl pyrrolidone) (PVP), and vinylpyrrolidone-vinyl acetate copolymer (VA64). The prepared SDs were characterized in terms of drug crystallinity, morphology, and in vitro dissolution profile in aqueous medium. The physical characterization using differential scanning calorimetry and X-ray powder diffraction revealed that the active compound was molecularly dispersed in all polymeric carriers tested, in a stable amorphous form in drug to polymer ratios ranging from 1:0.5 to 1:2. The dissolution rates of DRN in all SDs were much higher than those from the corresponding physical mixture and drug powder alone. In particular, the greatest dissolution enhancement was obtained from the VA64-based SD in a drug to polymer weight ratio of 1:1, achieving almost complete drug release after 120 min at pH 1.2. Thus, VA64-based SD with higher drug dissolution rate along with a simple preparation process is suggested as an alternative for the oral formulation of the benzofuran derivative.

  18. Solid dispersions, part I: recent evolutions and future opportunities in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

    Science.gov (United States)

    Bikiaris, Dimitrios N

    2011-11-01

    In recent years, the number of active pharmaceutical ingredients with high therapeutic impact, but very low water solubility, has increased significantly. Thus, a great challenge for pharmaceutical technology is to create new formulations and efficient drug-delivery systems to overcome these dissolution problems. Drug formulation in solid dispersions (SDs) is one of the most commonly used techniques for the dissolution rate enhancement of poorly water-soluble drugs. Generally, SDs can be defined as a dispersion of active ingredients in molecular, amorphous and/or microcrystalline forms into an inert carrier. This review covers literature which states that the dissolution enhancement of SDs is based on the fact that drugs in the nanoscale range, or in amorphous phase, dissolve faster and to a greater extent than micronized drug particles. This is in accordance to the Noyes-Whitney equation, while the wetting properties of the used polymer may also play an important role. The main factors why SD-based pharmaceutical products on the market are steadily increasing over the last few years are: the recent progress in various methods used for the preparation of SDs, the effect of evolved interactions in physical state of the drug and formulation stability during storage, the characterization of the physical state of the drug and the mechanism of dissolution rate enhancement.

  19. Impact of in situ polymer coating on particle dispersion into solid laser-generated nanocomposites.

    Science.gov (United States)

    Wagener, Philipp; Brandes, Gudrun; Schwenke, Andreas; Barcikowski, Stephan

    2011-03-21

    The crucial step in the production of solid nanocomposites is the uniform embedding of nanoparticles into the polymer matrix, since the colloidal properties or specific physical properties are very sensitive to particle dispersion within the nanocomposite. Therefore, we studied a laser-based generation method of a nanocomposite which enables us to control the agglomeration of nanoparticles and to increase the single particle dispersion within polyurethane. For this purpose, we ablated targets of silver and copper inside a polymer-doped solution of tetrahydrofuran by a picosecond laser (using a pulse energy of 125 μJ at 33.3 kHz repetition rate) and hardened the resulting colloids into solid polymers. Electron microscopy of these nanocomposites revealed that primary particle size, agglomerate size and particle dispersion strongly depend on concentration of the polyurethane added before laser ablation. 0.3 wt% polyurethane is the optimal polymer concentration to produce nanocomposites with improved particle dispersion and adequate productivity. Lower polyurethane concentration results in agglomeration whereas higher concentration reduces the production rate significantly. The following evaporation step did not change the distribution of the nanocomposite inside the polyurethane matrix. Hence, the in situ coating of nanoparticles with polyurethane during laser ablation enables simple integration into the structural analogue polymer matrix without additives. Furthermore, it was possible to injection mold these in situ-stabilized nanocomposites without affecting particle dispersion. This clarifies that sufficient in situ stabilization during laser ablation in polymer solution is able to prevent agglomeration even in a hot polymer melt.

  20. New metastable form of glibenclamide prepared by redispersion from ternary solid dispersions containing polyvinylpyrrolidone-K30 and sodium lauryl sulfate.

    Science.gov (United States)

    Thongnopkoon, Thanu; Puttipipatkhachorn, Satit

    2016-01-01

    Modification of polymorphic forms of poorly water-soluble drugs is one way to achieve the desirable properties. In this study, glibenclamide (GBM) particles with different polymorphic forms, including a new metastable form, were obtained from redispersion of ternary solid dispersion systems. The ternary solid dispersion systems, consisting of GBM, polyvinylpyrrolidone-K30 (PVP-K30) and sodium lauryl sulfate (SLS), were prepared by solvent evaporation method and subsequently redispersed in deionized water. The precipitated drug particles were then collected at a given time period. The drug particles with different polymorphic forms could be achieved depending on the polymer/surfactant ratio. Amorphous drug nanoparticles could be obtained by using a high polymer/surfactant ratio, whereas two different crystalline forms were obtained from the systems containing low polymer/surfactant ratios. Interestingly, a new metastable form IV of GBM with improved dissolution behavior could be obtained from the system of GBM:PVP-K30:SLS with the weight ratio of 2:2:4. This new polymorphic form IV of GBM was confirmed by differential scanning calorimetry (DSC), Fourier transform infrared (FT-IR) spectroscopy, powder X-ray diffractometry (PXRD) and solid state 13 C nuclear magnetic resonance (NMR) spectroscopy. The molecular arrangement of the new polymorphic form IV of GBM was proposed. The GBM particles with polymorphic form IV also showed an improved dissolution behavior. In addition, it was found that the formation of the new polymorphic form IV of GBM by this process was reproducible.

  1. Enriched Boron-Doped Amorphous Selenium Based Position-Sensitive Solid-State Thermal Neutron Detector for MPACT Applications

    Energy Technology Data Exchange (ETDEWEB)

    Mandal, Krishna [Univ. of South Carolina, Columbia, SC (United States)

    2017-09-29

    High-efficiency thermal neutron detectors with compact size, low power-rating and high spatial, temporal and energy resolution are essential to execute non-proliferation and safeguard protocols. The demands of such detector are not fully covered by the current detection system such as gas proportional counters or scintillator-photomultiplier tube combinations, which are limited by their detection efficiency, stability of response, speed of operation, and physical size. Furthermore, world-wide shortage of 3He gas, required for widely used gas detection method, has further prompted to design an alternative system. Therefore, a solid-state neutron detection system without the requirement of 3He will be very desirable. To address the above technology gap, we had proposed to develop new room temperature solidstate thermal neutron detectors based on enriched boron (10B) and enriched lithium (6Li) doped amorphous Se (As- 0.52%, Cl 5 ppm) semiconductor for MPACT applications. The proposed alloy materials have been identified for its many favorable characteristics - a wide bandgap (~2.2 eV at 300 K) for room temperature operation, high glass transition temperature (tg ~ 85°C), a high thermal neutron cross-section (for boron ~ 3840 barns, for lithium ~ 940 barns, 1 barn = 10-24 cm2), low effective atomic number of Se for small gamma ray sensitivity, and high radiation tolerance due to its amorphous structure.

  2. Enriched Boron-Doped Amorphous Selenium Based Position-Sensitive Solid-State Thermal Neutron Detector for MPACT Applications

    International Nuclear Information System (INIS)

    Mandal, Krishna

    2017-01-01

    High-efficiency thermal neutron detectors with compact size, low power-rating and high spatial, temporal and energy resolution are essential to execute non-proliferation and safeguard protocols. The demands of such detector are not fully covered by the current detection system such as gas proportional counters or scintillator-photomultiplier tube combinations, which are limited by their detection efficiency, stability of response, speed of operation, and physical size. Furthermore, world-wide shortage of 3 He gas, required for widely used gas detection method, has further prompted to design an alternative system. Therefore, a solid-state neutron detection system without the requirement of 3 He will be very desirable. To address the above technology gap, we had proposed to develop new room temperature solidstate thermal neutron detectors based on enriched boron ( 10 B) and enriched lithium ( 6 Li) doped amorphous Se (As- 0.52%, Cl 5 ppm) semiconductor for MPACT applications. The proposed alloy materials have been identified for its many favorable characteristics - a wide bandgap (~2.2 eV at 300 K) for room temperature operation, high glass transition temperature (t g ~ 85°C), a high thermal neutron cross-section (for boron ~ 3840 barns, for lithium ~ 940 barns, 1 barn = 10 -24 cm 2 ), low effective atomic number of Se for small gamma ray sensitivity, and high radiation tolerance due to its amorphous structure.

  3. Combinational approach using solid dispersion and semi-solid matrix technology to enhance in vitro dissolution of telmisartan

    Directory of Open Access Journals (Sweden)

    Syed Faisal Ali

    2016-02-01

    Full Text Available The present investigation was focused to formulate semi-solid capsules (SSCs of hydrophobic drug telmisartan (TLMS by encapsulating semi-solid matrix of its solid dispersion (SD in HPMC capsules. The combinational approach was used to reduce the lag time in drug release and improvise its dissolution. SDs of TLMS was prepared using hot fusion method by varying the combinations of Pluronic-F68, Gelucire 50/13 and Plasdone S630. A total of nine batches (SD1-SD9 were characterized for micromeritic properties, in vitro dissolution behavior and surface characterization. SD4 with 52.43% cumulative drug release (CDR in phosphate buffer, pH 7.4, in 120 min, t50% 44.2 min and DE30min 96.76% was selected for the development of semi-solid capsules. Differential scanning calorimetry of SD4 revealed molecular dispersion of TLMS in Pluronic-F68. SD4 was formulated into SSCs using Gelucire 44/14 and PEG 400 as semi-solid components and PEG 6000 as a suspending agent to achieve reduction in lag time for effective drug dissolution. SSC6 showed maximum in vitro drug dissolution 97.49 % in phosphate buffer, pH 7.4 with in 20 min that was almost a three folds reduction in the time required to achieve similar dissolution by SD. Thus, SSCs present an excellent approach to enhance in vitro dissolution as well as to reduce the lag time of dissolution for poorly water soluble drugs especially to those therapeutic classes that are intended for faster onset of action. Developed approach based on HPMC capsules provided a better alternative to target delivery of telmisartan to the vegetarian population.

  4. Novel Solid Encapsulation of Ethylene Gas Using Amorphous α-Cyclodextrin and the Release Characteristics.

    Science.gov (United States)

    Ho, Binh T; Bhandari, Bhesh R

    2016-05-04

    This research investigated the encapsulation of ethylene gas into amorphous α-cyclodextrins (α-CDs) at low (LM) and high (HM) moisture contents at 1.0-1.5 MPa for 24-120 h and its controlled release characteristics at 11.2-52.9% relative humidity (RH) for 1-168 h. The inclusion complexes (ICs) were characterized using X-ray diffractometry (XRD), nuclear magnetic resonance spectroscopy (CP-MAS (13)C NMR), and scanning electron microscopy (SEM). Ethylene concentrations in the ICs were from 0.45 to 0.87 mol of ethylene/mol CD and from 0.42 to 0.54 mol of ethylene/mol CD for LM and HM α-CDs, respectively. Ethylene gas released from the encapsulated powder at higher rates with increasing RH. An analysis of release kinetics using Avrami's equation showed that the LM and HM amorphous α-CDs were not associated with significant differences in release constant k and parameter n for any given RH condition. NMR spectra showed the presence of the characteristic carbon-carbon double bond of ethylene gas in the encapsulated α-CD powder.

  5. Solid state photochemistry. Subpanel A-2(b): Metastability in hydrogenated amorphous silicon

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, D. [Solarex Corporation, Newton, PA (United States)

    1996-09-01

    All device quality amorphous silicon based materials exhibit degradation in electronic properties when exposed to sunlight. The photo-induced defects are associated with Si dangling bonds that are created by the recombination and/or trapping of photogenerated carriers. The defects are metastable and can be annealed out at temperatures of about 150 to 200 degrees Centigrade. The density of metastable defects is larger in films that are contaminated with > 10{sup 19} per cubic cm of impurities such as oxygen, carbon and nitrogen. However, recent experimental results indicate that some metastable defects are still present in films with very low impurity concentrations. The photo-induced defects typically saturate after 100 to 1000 hours of exposure to one sun illumination depending on the deposition conditions. There is also experimental evidence that photo-induced structural changes are occurring in the amorphous silicon based materials and that hydrogen may be playing an important role in both the photo-induced structural changes and in the creation of metastable defects.

  6. Amorphous is not always better—A dissolution study on solid state forms of carbamazepine

    DEFF Research Database (Denmark)

    Jensen, Linda G.; Skautrup, Frederik B.; Müllertz, Anette

    2017-01-01

    state forms of carbamazepine, crystalline or amorphous drug, with or without either polyvinylpyrrolidone (PVP) or hydroxypropylmethylcellulose (HPMC) and glass solutions of the drug with both polymers (2:1, 4:1 and 10:1 (w/w) drug-to-polymer ratio) were tested with respect to their dissolution behaviour...... in a biorelevant gastric medium (for 30 min) and subsequently in intestinal conditions (for 2 h). Carbamazepine form III in the absence of polymer dissolved to a drug concentration of 540 μg/ml, but the concentration decreased after around 70 min due to precipitation of the dihydrate form, and reached 436 μg....../ml after 2.5 h dissolution testing. The presence of PVP led to a similar dissolution profile with a slightly earlier onset of decrease in drug concentration, while in the presence of HPMC no decline in dissolved drug concentration was observed. Surprisingly, amorphous carbamazepine did not result in any...

  7. Novel Transrotational Solid State Order Discovered by TEM in Crystallizing Amorphous Films

    Science.gov (United States)

    Kolosov, Vladimir

    Exotic thin crystals with unexpected transrotational microstructures have been discovered by transmission electron microscopy (TEM) for crystal growth in thin (10-100 nm) amorphous films of different chemical nature (oxides, chalcogenides, metals and alloys) prepared by various methods. Primarily we use our TEM bend contour technique. The unusual phenomenon can be traced in situ in TEM column: dislocation independent regular internal bending of crystal lattice planes in a growing crystal. Such transrotation (unit cell trans lation is complicated by small rotationrealized round an axis lying in the film plane) can result in strong regular lattice orientation gradients (up to 300 degrees per micrometer) of different geometries: cylindrical, ellipsoidal, toroidal, saddle, etc. Transrotation is increasing as the film gets thinner. Transrotational crystal resembles ideal single crystal enclosed in a curved space. Transrotational micro crystals have been eventually recognized by other authors in some vital thin film materials, i.e. PCMs for memory, silicides, SrTiO3. Atomic model and possible mechanisms of the phenomenon are discussed. New transrotational nanocrystalline model of amorphous state is also proposed Support of RF Ministry of Education and Science is acknowledged.

  8. Enhanced dissolution and bioavailability of Nateglinide by microenvironmental pH-regulated ternary solid dispersion: in-vitro and in-vivo evaluation.

    Science.gov (United States)

    Wairkar, Sarika; Gaud, Ram; Jadhav, Namdeo

    2017-09-01

    Nateglinide, an Antidiabetic drug (BCS II), shows pH-dependent solubility and variable bioavailability. The purpose of study was to increase dissolution and bioavailability of Nateglinide by development of its microenvironmental pH-regulated ternary solid dispersion (MeSD). MeSD formulation of Nateglinide, poloxamer-188 and Na 2 CO 3 was prepared by melt dispersion in 1 : 2 : 0.2 w/w ratio and further characterised for solubility, In-vitro dissolution, microenvironmental pH, crystallinity/amorphism, physicochemical interactions, bioavailability in Wistar rats. Solubility of Nateglinide was increased notably in MeSD, and its in-vitro dissolution study showed fourfold increase in the dissolution, particularly in 1.2 pH buffer. Prominent reduction in the peak intensity of X-ray powder diffraction (XRPD) and absence of endotherm in DSC thermogram confirmed the amorphism of Nateglinide in MeSD. Attenuated total reflectance Fourier transform infrared spectra revealed the hydrogen bond interactions between Nateglinide and poloxamer-188. In-vivo study indicated that MeSD exhibited fourfold increase in area under curve over Nateglinide. Tmax of MeSD was observed at 0.25 h, which is beneficial for efficient management of postprandial sugar. Instead of mere transformation of the Nateglinide to its amorphous form as evidenced by DSC and XRPD, formation of a soluble carboxylate compound of Nateglinide in MeSD was predominantly responsible for dissolution and bioavailability enhancement. The study demonstrates the utility of MeSD in achieving pH-independent dissolution, reduced T max and enhanced bioavailability of Nateglinide. © 2017 Royal Pharmaceutical Society.

  9. The photoexcitation of crystalline ice and amorphous solid water: A molecular dynamics study of outcomes at 11 K and 125 K

    Energy Technology Data Exchange (ETDEWEB)

    Crouse, J.; Loock, H.-P., E-mail: hploock@chem.queensu.ca; Cann, N. M., E-mail: ncann@chem.queensu.ca [Department of Chemistry, Queen’s University, Kingston, Ontario K7L 3N6 (Canada)

    2015-07-21

    Photoexcitation of crystalline ice Ih and amorphous solid water at 7-9 eV is examined using molecular dynamics simulations and a fully flexible water model. The probabilities of photofragment desorption, trapping, and recombination are examined for crystalline ice at 11 K and at 125 K and for amorphous solid water at 11 K. For 11 K crystalline ice, a fully rigid water model is also employed for comparison. The kinetic energy of desorbed H atoms and the distance travelled by trapped fragments are correlated to the location and the local environment of the photoexcited water molecule. In all cases, H atom desorption is found to be the most likely outcome in the top bilayer while trapping of all photofragments is most probable deeper in the solid where the likelihood for recombination of the fragments into H{sub 2}O molecules also rises. Trajectory analysis indicates that the local hydrogen bonding network in amorphous solid water is more easily distorted by a photodissociation event compared to crystalline ice. Also, simulations indicate that desorption of OH radicals and H{sub 2}O molecules are more probable in amorphous solid water. The kinetic energy distributions for desorbed H atoms show a peak at high energy in crystalline ice, arising from photoexcited water molecules in the top monolayer. This peak is less pronounced in amorphous solid water. H atoms that are trapped may be displaced by up to ∼10 water cages, but migrate on average 3 water cages. Trapped OH fragments tend to stay near the original solvent cage.

  10. Fast-track to a solid dispersion formulation using multi-way analysis of complex interactions

    DEFF Research Database (Denmark)

    Wu, Jian-Xiong; Den Berg, Frans Van; Søgaard, Søren Vinter

    2013-01-01

    Several factors with complex interactions influence the physical stability of solid dispersions, thus highlighting the need for efficient experimental design together with robust and simple multivariate model. Design of Experiments together with ANalysis Of VAriance (ANOVA) model is one of the ce.......g., an entire spectral data set), model uniqueness, and curve resolution abilities. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:904-914, 2013....

  11. To evaluate the change in release from solid dispersion using sodium lauryl sulfate and model drug sulfathiazole.

    Science.gov (United States)

    Dave, Rutesh H; Patel, Hardikkumar H; Donahue, Edward; Patel, Ashwinkumar D

    2013-10-01

    The solubility of drugs remains one of the most challenging aspects of formulation development. There are numerous ways to improve the solubility of drugs amongst which the most promising strategy is solid dispersion. Different ratios of sulfathiazole: PVP-K29/32: sodium lauryl sulfate (SLS) were prepared (1:1:0.1, 1:1:0.5, 1:1:1) and various methods were employed to characterize the prepared solid dispersions, namely modulated differential scanning calorimeter, X-ray powder diffraction, Fourier Transformed Infrared Spectroscopy and dissolution studies. Lack of crystallinity was observed in internal and external systems suggesting a loss of crystallinity, whereas the physical mixtures showed a characteristic peak of sulfathiazole. In vitro dissolution results clearly showed that the incorporation of a relatively small amount of surfactants (5, 20 or 33% w/w) into a solid dispersion can improve its dissolution rates compared to binary solid dispersion (SD) alone and pure sulfathiazole. In all ratios solid dispersion internal shows a higher dissolution rate compared to a physical mixture and solid dispersion external which suggests that the way that the surfactant is incorporated into the solid dispersion plays an important role in changing the solubility of a drug. The solubilization mechanism is mainly responsible for this higher dissolution rate when we incorporate the SLS in SD.

  12. Scattering of light keV ions from amorphous and crystalline solid surfaces

    International Nuclear Information System (INIS)

    Robinson, J.E.; Kwok, K.K.; Thompson, D.A.

    1976-01-01

    Total reflection coefficients (R), backscattered energy fractions (γ), and backscattered energy spectra are evaluated using a binary collision Monte Carlo technique for a variety of light ions (H, D, T, He) in the energy range 0.25-8 keV, incident on amorphous targets (C, Fe, Nb). The scattering is also evaluated for H on Nb for a range of incident angles and two electronic stopping values. The average scattered energy per reflected particle and the backscattered energy spectra are found to vary in a universal manner as a function of the reflection coefficient between the Rutherford high energy limit and a low energy multiple collision limit. Single crystal effects are also briefly discussed using a diffusional dechanneling model. (Auth.)

  13. Solid-state properties and dissolution behaviour of tablets containing co-amorphous indomethacin-arginine

    DEFF Research Database (Denmark)

    Lenz, Elisabeth; Jensen, Katrine Birgitte Tarp; Blaabjerg, Lasse Ingerslev

    2015-01-01

    –arginine in a larger production scale. In this work, a tablet formulation was developed for a co-amorphous salt, namely spray dried indomethacin–arginine (SD IND–ARG). The effects of compaction pressure on tablet properties, physical stability and dissolution profiles under non-sink conditions were examined....... Dissolution profiles of tablets with SD IND–ARG (TAB SD IND–ARG) were compared to those of tablets containing a physical mixture of crystalline IND and ARG (TAB PM IND–ARG) and to the dissolution of pure spray dried powder. Concerning tableting, the developed formulation allowed for the preparation of tablets...... with a broad range of compaction pressures resulting in different porosities and tensile strengths. XRPD results showed that, overall, no crystallization occurred neither during tableting nor during long-term storage. Dissolution profiles of TAB SD IND–ARG showed an immediate release of IND by erosion...

  14. Electron-beam-irradiation-induced crystallization of amorphous solid phase change materials

    Science.gov (United States)

    Zhou, Dong; Wu, Liangcai; Wen, Lin; Ma, Liya; Zhang, Xingyao; Li, Yudong; Guo, Qi; Song, Zhitang

    2018-04-01

    The electron-beam-irradiation-induced crystallization of phase change materials in a nano sized area was studied by in situ transmission electron microscopy and selected area electron diffraction. Amorphous phase change materials changed to a polycrystalline state after being irradiated with a 200 kV electron beam for a long time. The results indicate that the crystallization temperature strongly depends on the difference in the heteronuclear bond enthalpy of the phase change materials. The selected area electron diffraction patterns reveal that Ge2Sb2Te5 is a nucleation-dominated material, when Si2Sb2Te3 and Ti0.5Sb2Te3 are growth-dominated materials.

  15. Hypercrosslinked particles for the extraction of sweeteners using dispersive solid-phase extraction from environmental samples.

    Science.gov (United States)

    Lakade, Sameer S; Zhou, Qing; Li, Aimin; Borrull, Francesc; Fontanals, Núria; Marcé, Rosa M

    2018-04-01

    This work presents a new extraction material, namely, Q-100, based on hypercrosslinked magnetic particles, which was tested in dispersive solid-phase extraction for a group of sweeteners from environmental samples. The hypercrosslinked Q-100 magnetic particles had the advantage of suitable pore size distribution and high surface area, and showed good retention behavior toward sweeteners. Different dispersive solid-phase extraction parameters such as amount of magnetic particles or extraction time were optimized. Under optimum conditions, Q-100 showed suitable apparent recovery, ranging in the case of river water sample from 21 to 88% for all the sweeteners, except for alitame (12%). The validated method based on dispersive solid-phase extraction using Q-100 followed by liquid chromatography with tandem mass spectrometry provided good linearity and limits of quantification between 0.01 and 0.1 μg/L. The method was applied to analyze samples from river water and effluent wastewater, and four sweeteners (acesulfame, saccharin, cyclamate, and sucralose) were found in both types of sample. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Development and Optimization of Osmotically Controlled Asymmetric Membrane Capsules for Delivery of Solid Dispersion of Lycopene

    Directory of Open Access Journals (Sweden)

    Nitin Jain

    2014-01-01

    Full Text Available The aim of the present investigation is to develop and statistically optimize the osmotically controlled asymmetric membrane capsules of solid dispersion of lycopene. Solid dispersions of lycopene with β-cyclodextrin in different ratios were prepared using solvent evaporation method. Solubility studies showed that the solid dispersion with 1 : 5 (lycopene : β-cyclodextrin exhibited optimum solubility (56.25 mg/mL for osmotic controlled delivery. Asymmetric membrane capsules (AMCs were prepared on glass mold pins via dip coating method. Membrane characterization by scanning electron microscopy showed inner porous region and outer dense region. Central composite design response surface methodology was applied for the optimization of AMCs. The independent variables were ethyl cellulose (X1, glycerol (X2, and NaCl (X3 which were varied at different levels to analyze the effect on dependent variables (percentage of cumulative drug release (Y1 and correlation coefficient of drug release (Y2. The effect of independent variables on the response was significantly influential. The F18 was selected as optimized formulation based on percentage of CDR (cumulative drug release of 85.63% and correlation coefficient of 0.9994. The optimized formulation was subjected to analyze the effect of osmotic pressure and agitational intensity on percentage of CDR. The drug release was independent of agitational intensity but was dependent on osmotic pressure of dissolution medium.

  17. Influence of solvent evaporation rate and formulation factors on solid dispersion physical stability.

    Science.gov (United States)

    Wu, Jian X; Yang, Mingshi; Berg, Frans van den; Pajander, Jari; Rades, Thomas; Rantanen, Jukka

    2011-12-18

    New chemical entities (NCEs) often show poor water solubility necessitating solid dispersion formulation. The aim of the current study is to employ design of experiments in investigating the influence of one critical process factor (solvent evaporation rate) and two formulation factors (PVP:piroxicam ratio (PVP:PRX) and PVP molecular weight (P(MW))) on the physical stability of PRX solid dispersion prepared by the solvent evaporation method. The results showed the rank order of an increase in factors contributing to a decrease in the extent of PRX nucleation being evaporation rate>PVP:PRX>P(MW). The same rank order was found for the decrease in the extent of PRX crystal growth in PVP matrices from day 0 up to day 12. However, after 12days the rank became PVP:PRX>evaporation rate>P(MW). The effects of an increase in evaporation rate and PVP:PRX ratio in stabilizing PRX were of the same order of magnitude, while the effect from P(MW) was much smaller. The findings were confirmed by XRPD. FT-IR showed that PRX recrystallization in the PVP matrix followed Ostwald's step rule, and an increase in the three factors all led to increased hydrogen bonding interaction between PRX and PVP. The present study showed the applicability of the Quality by Design approach in solid dispersion research, and highlights the need for multifactorial analysis. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Comparison of ethylcellulose matrix characteristics prepared by solid dispersion technique or physical mixing

    Directory of Open Access Journals (Sweden)

    Fatemeh Sadeghi

    2003-07-01

    Full Text Available The characteristics of ethylcellulose matrices prepared from solid dispersion systems were compared with those prepared from physical mixture of drug and polymer. Sodium diclofenac was used as a model drug and the effect of the drug:polymer ratio and the method of matrix production on tablet crushing strength, friability, drug release profile and drug release mechanism were evaluated. The results showed that increasing the polymer content in matrices increased the crushing strengths of tablets. However the friability of tablets was independent of polymer content. Drug release rate was greatly affected by the amount of polymer in the matrices and considerable decrease in release rate was observed by increasing the polymer content. It was also found that the type of mixture used for matrix production had great influence on the tablet crushing strength and drug release rate. Matrices prepared from physical mixtures of drug and polymer was harder than those prepared from solid dispersion systems, but their release rates were considerably faster. This phenomenon was attributed to the encapsulation of drug particles by polymer in matrices prepared from solid dispersion system which caused a great delay in diffusion of the drug through polymer and made diffusion as a rate retarding process in drug release mechanism.

  19. Emerging trends in the stabilization of amorphous drugs

    DEFF Research Database (Denmark)

    Laitinen, Riikka; Löbmann, Korbinian; Strachan, Clare J.

    2013-01-01

    The number of active pharmaceutical substances having high therapeutic potential but low water solubility is constantly increasing, making it difficult to formulate these compounds as oral dosage forms. The solubility and dissolution rate, and thus potentially the bioavailability, of these poorly...... water-soluble drugs can be increased by the formation of stabilized amorphous forms. Currently, formulation as solid polymer dispersions is the preferred method to enhance drug dissolution and to stabilize the amorphous form of a drug. The purpose of this review is to highlight emerging alternative...... of mesoporous silicon and silica-based carriers are presented as potential means to increase the stability of amorphous pharmaceuticals....

  20. The potential for the fabrication of wires embedded in the crystalline silicon substrate using the solid phase segregation of gold in crystallising amorphous volumes

    International Nuclear Information System (INIS)

    Liu, A.C.Y.; McCallum, J.C.

    2004-01-01

    The refinement of gold in crystallising amorphous silicon volumes was tested as a means of creating a conducting element embedded in the crystalline matrix. Amorphous silicon volumes were created by self-ion-implantation through a mask. Five hundred kiloelectronvolt Au + was then implanted into the volumes. The amorphous volumes were crystallised on a hot stage in air, and the crystallisation was characterised using cross sectional transmission electron microscopy. It was found that the amorphous silicon volumes crystallised via solid phase epitaxy at all the lateral and vertical interfaces. The interplay of the effects of the gold and also the hydrogen that infilitrated from the surface oxide resulted in a plug of amorphous material at the surface. Further annealing at this temperature demonstrated that the gold, once it had reached a certain critical concentration nucleated poly-crystalline growth instead of solid phase epitaxy. Time resolved reflectivity and Rutherford backscattering and channeling measurements were performed on large area samples that had been subject to the same implantation regime to investigate this system further. It was discovered that the crystallisation dynamics and zone refinement of the gold were complicated functions of both gold concentration and temperature. These findings do not encourage the use of this method to obtain conducting elements embedded in the crystalline silicon substrate

  1. Preparation and Characterization of Solid Dispersions of Artemether by Freeze-Dried Method

    Directory of Open Access Journals (Sweden)

    Muhammad Tayyab Ansari

    2015-01-01

    Full Text Available Solid dispersions of artemether and polyethylene glycol 6000 (PEG6000 were prepared in ratio 12 : 88 (group-1. Self-emulsified solid dispersions of artemether were prepared by using polyethylene glycol 6000, Cremophor-A25, olive oil, Transcutol, and hydroxypropyl methylcellulose (HPMC in ratio 12 : 75 : 5 : 4 : 2 : 2, respectively (group-2. In third group, only Cremophor-A25 was replaced with Poloxamer 188 compared to group-2. The solid dispersions and self-emulsified solid dispersions were prepared by physical and freeze dried methods, respectively. All samples were characterized by X-ray diffraction, attenuated total reflectance Fourier transform infrared spectroscopy, differential scanning calorimeter, scanning electron microscopy, and solubility, dissolution, and stability studies. X-ray diffraction pattern revealed artemether complete crystalline, whereas physical mixture and freeze-dried mixture of all three groups showed reduced peak intensities. In attenuated total reflectance Fourier transform infrared spectroscopy spectra, C–H stretching vibrations of artemether were masked in all prepared samples, while C–H stretching vibrations were representative of polyethylene glycol 6000, Cremophor-A25, and Poloxamer 188. Differential scanning calorimetry showed decreased melting endotherm and increased enthalpy change (ΔH in both physical mixture and freeze-dried mixtures of all groups. Scanning electron microscopy of freeze-dried mixtures of all samples showed glassy appearance, size reduction, and embedment, while their physical mixture showed size reduction and embedment of artemether by excipients. In group-1, solubility was improved up to 15 times, whereas group-2 showed up to 121 times increase but, in group-3, when Poloxamer 188 was used instead of Cremophor-A25, solubility of freeze-dried mixtures was increased up to 135 times. In fasted state simulated gastric fluid at pH 1.6, the dissolution of physical

  2. Excess vibrational density of states and the brittle to ductile transition in crystalline and amorphous solids.

    Science.gov (United States)

    Babu, Jeetu S; Mondal, Chandana; Sengupta, Surajit; Karmakar, Smarajit

    2016-01-28

    The conditions which determine whether a material behaves in a brittle or ductile fashion on mechanical loading are still elusive and comprise a topic of active research among materials physicists and engineers. In this study, we present the results of in silico mechanical deformation experiments from two very different model solids in two and three dimensions. The first consists of particles interacting with isotropic potentials and the other has strongly direction dependent interactions. We show that in both cases, the excess vibrational density of states is one of the fundamental quantities which characterizes the ductility of the material. Our results can be checked using careful experiments on colloidal solids.

  3. Near-infrared analysis of hydrogen-bonding in glass- and rubber-state amorphous saccharide solids.

    Science.gov (United States)

    Izutsu, Ken-ichi; Hiyama, Yukio; Yomota, Chikako; Kawanishi, Toru

    2009-01-01

    Near-infrared (NIR) spectroscopic analysis of noncrystalline polyols and saccharides (e.g., glycerol, sorbitol, maltitol, glucose, sucrose, maltose) was performed at different temperatures (30-80 degrees C) to elucidate the effect of glass transition on molecular interaction. Transmission NIR spectra (4,000-12,000 cm(-1)) of the liquids and cooled-melt amorphous solids showed broad absorption bands that indicate random configuration of molecules. Heating of the samples decreased an intermolecular hydrogen-bonding OH vibration band intensity (6,200-6,500 cm(-1)) with a concomitant increase in a free and intramolecular hydrogen-bonding OH group band (6,600-7,100 cm(-1)). Large reduction of the intermolecular hydrogen-bonding band intensity at temperatures above the glass transition (T(g)) of the individual solids should explain the higher molecular mobility and lower viscosity in the rubber state. Mixing of the polyols with a high T(g) saccharide (maltose) or an inorganic salt (sodium tetraborate) shifted both the glass transition and the inflection point of the hydrogen-bonding band intensity to higher temperatures. The implications of these results for pharmaceutical formulation design and process monitoring (PAT) are discussed.

  4. Evaluation of single-walled carbon nanohorns as sorbent in dispersive micro solid-phase extraction

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez-Soto, Juan Manuel; Cardenas, Soledad [Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, Marie Curie Building, Campus de Rabanales, University of Cordoba, 14071 Cordoba (Spain); Valcarcel, Miguel, E-mail: qa1meobj@uco.es [Department of Analytical Chemistry, Institute of Fine Chemistry and Nanochemistry, Marie Curie Building, Campus de Rabanales, University of Cordoba, 14071 Cordoba (Spain)

    2012-02-10

    Highlights: Black-Right-Pointing-Pointer The potential of single walled carbon nanohorns in dispersive solid phase microextraction has been evaluated. Black-Right-Pointing-Pointer The method was characterized for the extraction of PAHs from waters. Black-Right-Pointing-Pointer Single walled carbon nanohorns were better extractant than carbon nanotubes and carbon nanocones. Black-Right-Pointing-Pointer The limits of detection were adequate for the target analytes in environmental waters. - Abstract: A new dispersive micro solid-phase extraction method which uses single-walled carbon nanohorns (SWNHs) as sorbent is proposed. The procedure combines the excellent sorbent properties of the nanoparticles with the efficiency of the dispersion of the material in the sample matrix. Under these conditions, the interaction with the analytes is maximized. The determination of polycyclic aromatic hydrocarbons was selected as model analytical problem. Two dispersion strategies were evaluated, being the functionalization via microwave irradiation better than the use of a surfactant. The extraction was accomplished by adding 1 mL of oxidized SWHNs (o-SWNHs) dispersion to 10 mL of water sample. After extraction, the mixture was passed through a disposable Nylon filter were the nanoparticles enriched with the PAHs were retained. The elution was carried out with 100 {mu}L of hexane. The limits of detection achieved were between 30 and 60 ng L{sup -1} with a precision (as repeatability) better than 12.5%. The recoveries obtained for the analytes in three different water samples were acceptable in all instances. The performance of o-SWNHs was favourably compared with that provided by carboxylated single-walled carbon nanotubes and thermally treated carbon nanocones.

  5. Amorphous chalcogenides as random octahedrally bonded solids: I. Implications for the first sharp diffraction peak, photodarkening, and Boson peak

    Science.gov (United States)

    Lukyanov, Alexey; Lubchenko, Vassiliy

    2017-09-01

    We develop a computationally efficient algorithm for generating high-quality structures for amorphous materials exhibiting distorted octahedral coordination. The computationally costly step of equilibrating the simulated melt is relegated to a much more efficient procedure, viz., generation of a random close-packed structure, which is subsequently used to generate parent structures for octahedrally bonded amorphous solids. The sites of the so-obtained lattice are populated by atoms and vacancies according to the desired stoichiometry while allowing one to control the number of homo-nuclear and hetero-nuclear bonds and, hence, effects of the mixing entropy. The resulting parent structure is geometrically optimized using quantum-chemical force fields; by varying the extent of geometric optimization of the parent structure, one can partially control the degree of octahedrality in local coordination and the strength of secondary bonding. The present methodology is applied to the archetypal chalcogenide alloys AsxSe1-x. We find that local coordination in these alloys interpolates between octahedral and tetrahedral bonding but in a non-obvious way; it exhibits bonding motifs that are not characteristic of either extreme. We consistently recover the first sharp diffraction peak (FSDP) in our structures and argue that the corresponding mid-range order stems from the charge density wave formed by regions housing covalent and weak, secondary interactions. The number of secondary interactions is determined by a delicate interplay between octahedrality and tetrahedrality in the covalent bonding; many of these interactions are homonuclear. The present results are consistent with the experimentally observed dependence of the FSDP on arsenic content, pressure, and temperature and its correlation with photodarkening and the Boson peak. They also suggest that the position of the FSDP can be used to infer the effective particle size relevant for the configurational equilibration in

  6. Silica Modified with Polyaniline as a Potential Sorbent for Matrix Solid Phase Dispersion (MSPD) and Dispersive Solid Phase Extraction (d-SPE) of Plant Samples

    Science.gov (United States)

    Sowa, Ireneusz; Wójciak-Kosior, Magdalena; Strzemski, Maciej; Sawicki, Jan; Staniak, Michał; Dresler, Sławomir; Szwerc, Wojciech; Mołdoch, Jarosław; Latalski, Michał

    2018-01-01

    Polyaniline (PANI) is one of the best known conductive polymers with multiple applications. Recently, it was also used in separation techniques, mostly as a component of composites for solid-phase microextraction (SPME). In the present paper, sorbent obtained by in situ polymerization of aniline directly on silica gel particles (Si-PANI) was used for dispersive solid phase extraction (d-SPE) and matrix solid–phase extraction (MSPD). The efficiency of both techniques was evaluated with the use of high performance liquid chromatography with diode array detection (HPLC-DAD) quantitative analysis. The quality of the sorbent was verified by Raman spectroscopy and microscopy combined with automated procedure using computer image analysis. For extraction experiments, triterpenes were chosen as model compounds. The optimal conditions were as follows: protonated Si-PANI impregnated with water, 160/1 sorbent/analyte ratio, 3 min of extraction time, 4 min of desorption time and methanolic solution of ammonia for elution of analytes. The proposed procedure was successfully used for pretreatment of plant samples. PMID:29565297

  7. Silica Modified with Polyaniline as a Potential Sorbent for Matrix Solid Phase Dispersion (MSPD and Dispersive Solid Phase Extraction (d-SPE of Plant Samples

    Directory of Open Access Journals (Sweden)

    Ireneusz Sowa

    2018-03-01

    Full Text Available Polyaniline (PANI is one of the best known conductive polymers with multiple applications. Recently, it was also used in separation techniques, mostly as a component of composites for solid-phase microextraction (SPME. In the present paper, sorbent obtained by in situ polymerization of aniline directly on silica gel particles (Si-PANI was used for dispersive solid phase extraction (d-SPE and matrix solid–phase extraction (MSPD. The efficiency of both techniques was evaluated with the use of high performance liquid chromatography with diode array detection (HPLC-DAD quantitative analysis. The quality of the sorbent was verified by Raman spectroscopy and microscopy combined with automated procedure using computer image analysis. For extraction experiments, triterpenes were chosen as model compounds. The optimal conditions were as follows: protonated Si-PANI impregnated with water, 160/1 sorbent/analyte ratio, 3 min of extraction time, 4 min of desorption time and methanolic solution of ammonia for elution of analytes. The proposed procedure was successfully used for pretreatment of plant samples.

  8. INVESTIGATION OF THE PHARMACO-TECHNOLOGICAL PROPERTIES OF SOLID DISPERSIONS OF THIOCTIC ACID, OBTAINED BY MICRONIZATION

    Directory of Open Access Journals (Sweden)

    Kovalevska, I. V.

    2018-04-01

    Full Text Available Introduction. Thioctic acid is used in the treatment of diseases that are characterized by lack of mitochondrial activity, which is responsible for the formation of free radicals. Widespread use of thioctic acid is due to the chemical structure. The thioctic acid exhibits biological activity in both hydrophilic and hydrophobic environments. Thioctic acid is an enzyme cofactor and a powerful antioxidant, it regulates the transcription of numerous genes, participates in regulation of glucose and lipid metabolism, increases insulin sensitivity, and forms complexes with heavy metals. Thioctic acid has a high pharmacological potential, which is confirmed by the evidence base of clinical trials. An analysis of the literature on the oral use of thioctic acid indicates that solid dosage forms can be used for long-term therapy. This route of administration is limited by factors such as reduced solubility in acidic environments and enzymatic degradation. For this reason, the search for various compositions of auxiliary substances and methods of obtaining drugs is an urgent task of pharmaceutical technology. Material & methods. Objects of study were solid dispersions of thioctic acid (SDTA on the basis of cellulose derivatives: microcrystalline (MCC, HPMC (hydroxypropyl methylcellulose and polyvinylpyrrolidone (PVP as compared to thioctic acid (TA. The samples were made by solid phase method using micronization in a laboratory shredder at a ratio of 1: 1. Pharmacological and technological parameters were determined according to generally accepted methods. Results & discussion. In appearance the resulting mixtures had lemon color, without inclusions and the formation of conglomerates, with homogeneous sized particles According to the pharmaco-technological studies, the samples do not have a satisfactory flowability. The values of the Carr index and the ratio of Hausner make it possible to conclude that there is a large force of cohesion between the

  9. Solubility and dissolution enhancement of flurbiprofen by solid dispersion using hydrophilic carriers

    Directory of Open Access Journals (Sweden)

    Bhaskar Daravath

    2018-05-01

    Full Text Available ABSTRACT The intent of the current work is to study the effect of polyethylene glycol 8000 and polyethylene glycol 10000 as hydrophilic carriers on dissolution behaviour of flurbiprofen. In the present study, solvent evaporation method was used to prepare flurbiprofen solid dispersions and evaluated for physico-chemical properties, drug-carrier compatibility studies and dissolution behaviour of drug. Solubility studies showed more solubility in higher pH values and formulations SD4 and SD8 were selected to prepare the fast dissolving tablets. FTIR and DSC study showed no interaction and drug was dispersed molecularly in hydrophilic carrier. XRD studies revealed that there was change in the crystallinity of the drug. The results of In vitro studies showed SD8 formulation confer significant improvement (p<0.05 in drug release, Q20 was 99.08±1.35% compared to conventional and marketed tablets (47.31±0.74% and 56.86±1.91%. The mean dissolution time (MDT was reduced to 8.79 min compared to conventional and marketed tablets (25.76 and 22.22 min. indicating faster drug release. The DE (% dissolution efficiency was increased by 2.5 folds (61.63% compared to conventional tablets (23.71%. From the results, it is evident that polyethylene glycol solid dispersions in less carrier ratio may enhance the solubility and there by improve the dissolution rate of flurbiprofen.

  10. On-cartridge derivatisation using matrix solid phase dispersion for the determination of cyclamate in foods

    International Nuclear Information System (INIS)

    Li, Jianjun; Liu, Yun; Liu, Qianping; Hui, Junfeng; Liu, Yangzi

    2017-01-01

    A novel method for determination of sodium cyclamate in foods was developed. In this method, a syringe was loaded with the homogeneous mixture of the sample, KMnO 4 powder and silica dispersant and used as a matrix solid phase dispersion (MSPD) reactor. As the reactor was infiltrated with small amounts of concentrated HCl, cyclamate was converted to 2-chlorocyclohexanone quickly and effectively within 5 min and determined by HPLC on a reversed-phase column using UV detection at a wavelength of 310 nm. Comparing with the traditional derivatisation in solution, the better clean-up was provided using on-cartridge derivatisation of MSPD, and much time, labor, and expense were saved. The results showed good linearity (r 2  = 0.9998) over the concentration range of 1–500 mg/L. The limit of detection (LOD) and limits of quantification (LOQ) of the cyclamate were 0.3 mg/L and 1 mg/L respectively. The recoveries ranged from 91.6% to 101.3% with the relative standard deviations (RSDs) in the range of 2.5%–4.3%. - Highlights: • A novel method was developed for the determination of cyclamate in foods. • On cartridge derivatisation, using matrix solid phase dispersion, was developed. • A new derivatisation reaction for cyclamate conversion to 2-chlorocyclohexanone was developed. • The method was rapid, simple, inexpensive, effective.

  11. On-cartridge derivatisation using matrix solid phase dispersion for the determination of cyclamate in foods

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jianjun, E-mail: bootan12@126.com [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Northwest University, Xi' an 710069 (China); National Engineering Research Center for Miniaturized Detection Systems, Xi' an 710069 (China); Liu, Yun [College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi' an 710062 (China); Liu, Qianping [National Engineering Research Center for Miniaturized Detection Systems, Xi' an 710069 (China); Hui, Junfeng [Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education, Northwest University, Xi' an 710069 (China); Liu, Yangzi [National Engineering Research Center for Miniaturized Detection Systems, Xi' an 710069 (China)

    2017-06-15

    A novel method for determination of sodium cyclamate in foods was developed. In this method, a syringe was loaded with the homogeneous mixture of the sample, KMnO{sub 4} powder and silica dispersant and used as a matrix solid phase dispersion (MSPD) reactor. As the reactor was infiltrated with small amounts of concentrated HCl, cyclamate was converted to 2-chlorocyclohexanone quickly and effectively within 5 min and determined by HPLC on a reversed-phase column using UV detection at a wavelength of 310 nm. Comparing with the traditional derivatisation in solution, the better clean-up was provided using on-cartridge derivatisation of MSPD, and much time, labor, and expense were saved. The results showed good linearity (r{sup 2} = 0.9998) over the concentration range of 1–500 mg/L. The limit of detection (LOD) and limits of quantification (LOQ) of the cyclamate were 0.3 mg/L and 1 mg/L respectively. The recoveries ranged from 91.6% to 101.3% with the relative standard deviations (RSDs) in the range of 2.5%–4.3%. - Highlights: • A novel method was developed for the determination of cyclamate in foods. • On cartridge derivatisation, using matrix solid phase dispersion, was developed. • A new derivatisation reaction for cyclamate conversion to 2-chlorocyclohexanone was developed. • The method was rapid, simple, inexpensive, effective.

  12. Supercooled and glassy water: Metastable liquid(s), amorphous solid(s), and a no-man's land

    Science.gov (United States)

    Handle, Philip H.; Loerting, Thomas; Sciortino, Francesco

    2017-12-01

    We review the recent research on supercooled and glassy water, focusing on the possible origins of its complex behavior. We stress the central role played by the strong directionality of the water-water interaction and by the competition between local energy, local entropy, and local density. In this context we discuss the phenomenon of polyamorphism (i.e., the existence of more than one disordered solid state), emphasizing both the role of the preparation protocols and the transformation between the different disordered ices. Finally, we present the ongoing debate on the possibility of linking polyamorphism with a liquid-liquid transition that could take place in the no-man's land, the temperature-pressure window in which homogeneous nucleation prevents the investigation of water in its metastable liquid form.

  13. Acid functionalized, highly dispersed carbonaceous spheres: an effective solid acid for hydrolysis of polysaccharides

    Science.gov (United States)

    Jiang, Yijun; Li, Xiutao; Cao, Quan; Mu, Xindong

    2011-02-01

    Highly dispersed carbonaceous spheres with sulfonic acid groups were successfully prepared from glucose by hydrothermal method. Transmission electron microscopy (TEM) showed the as-synthesized carbonaceous materials were uniform, spherical in shape with an average diameter of about 450 nm. Fourier transform infrared (FT-IR) proved that -SO3H, -COOH, OH groups were grafted on the surface of the carbonaceous spheres during the sulfonation. Interestingly, the functionalized carbonaceous spheres exhibited high dispersibility in the polar solvent due to the hydrophilic groups on the surface. The mechanism of the formation for the carbonaceous spheres was also discussed based on the analysis of structure and composition. At last, the functionalized carbonaceous spheres were employed as solid acid to hydrolyze starch and cellulose. By comparison, the as-synthesized catalyst showed considerable high yield of glucose.

  14. Acid functionalized, highly dispersed carbonaceous spheres: an effective solid acid for hydrolysis of polysaccharides

    International Nuclear Information System (INIS)

    Jiang Yijun; Li Xiutao; Cao Quan; Mu Xindong

    2011-01-01

    Highly dispersed carbonaceous spheres with sulfonic acid groups were successfully prepared from glucose by hydrothermal method. Transmission electron microscopy (TEM) showed the as-synthesized carbonaceous materials were uniform, spherical in shape with an average diameter of about 450 nm. Fourier transform infrared (FT-IR) proved that –SO 3 H, –COOH, OH groups were grafted on the surface of the carbonaceous spheres during the sulfonation. Interestingly, the functionalized carbonaceous spheres exhibited high dispersibility in the polar solvent due to the hydrophilic groups on the surface. The mechanism of the formation for the carbonaceous spheres was also discussed based on the analysis of structure and composition. At last, the functionalized carbonaceous spheres were employed as solid acid to hydrolyze starch and cellulose. By comparison, the as-synthesized catalyst showed considerable high yield of glucose.

  15. Luminescence in amorphous silicon p-i-n diodes under double-injection dispersive-transport-controlled recombination

    International Nuclear Information System (INIS)

    Han, D.; Wang, K.; Yeh, C.; Yang, L.; Deng, X.; Von Roedern, B.

    1997-01-01

    The temperature and electric-field dependence of the forward bias current and the electroluminescence (EL) in hydrogenated amorphous silicon (a-Si:H) p-i-n and n-i-p diodes have been studied. Both the current and the EL efficiency temperature dependence show three regions depending on either hopping-controlled or multiple-trapping or ballistic transport mechanisms. Comparing the thermalization-controlled geminate recombination processes of photoluminescence to the features of EL, the differences can be explained by transport-controlled nongeminate recombination in trap-rich materials. copyright 1997 The American Physical Society

  16. Study of the pressure-time-temperature transformation of amorphous La6Ni5Al89 by the energy dispersive method for phase transition

    DEFF Research Database (Denmark)

    Paci, B.; Rossi-Albertini, V.; Sikorski, M.

    2005-01-01

    An energy dispersive X-ray diffraction method to observe phase transitions is applied to follow the crystallization of an amorphous alloy (La6Ni5Al89) in isothermal conditions. In this way, the diffraction-based configurational entropy (DCE) of the system undergoing the phase transformations...... was measured and the curves describing the transitions, qualitatively equivalent to a differential scanning calorimetry (DSC) thermogram, could be drawn. Finally, the analysis of such curves allowed calculation of some points of the alloy pressure-time-temperature transformation (PTTT) diagram. More...... importantly, the present work shows that the DCE method can be successfully applied even when DSC can no longer be used. As a consequence, regions of the phase diagram that could not be reached up to now become accessible, opening the way to the study of transition phenomena under extreme conditions....

  17. The kinetics of solid phase epitaxy in As-doped buried amorphous silicon layers

    International Nuclear Information System (INIS)

    McCallum, J.C.

    1998-01-01

    The kinetics of dopant-enhanced solid phase epitaxy (SPE) have been measured in buried a-Si layers doped with arsenic. SPE rates were measured over the temperature range 480 - 660 deg C for buried a-Si layers containing ten different As concentrations. In the absence of H-retardation effects, the dopant-enhanced SPE rate is observed to depend linearly on the As concentration over the entire range of concentrations, 1-16 x 10 19 cm -3 covered in the study. The Fermi level energy was calculated as a function of doping and find an equation that can provide good fits to the data. The implications of these results for models of the SPE process is discussed

  18. Problems on one-dimensionally disordered lattices, and reliability of structural analysis of liquids and amorphous solids

    International Nuclear Information System (INIS)

    Kakinoki, J.

    1974-01-01

    Methods for obtaining the intensity of X-ray diffraction by one-dimensional by disordered lattices have been studied, and matrix method was developed. The method has been applied for structural analysis. Several problems concerning neutron diffraction were shown in the course of analysis. Large single crystals should be used for measurement. It is hard to grasp the local variation of structure. The technique of topography is still in development. Measurement of weak intensity diffraction is not sufficient. Technique of photography to observe overall feature is not good. General remarks concerning the one-dimensionally disordered lattices are as follows. A large number of parameters for analysis are not practical, and the disorder parameters are preferably two. In case of the disorder between two kinds of layers having same frequency and different structure, peak shift is not caused, and Laue term remains at the position. Reliability of the structural analysis of liquid and amorphous solid is discussed. The analysis is basically the analysis two atom molecule of same kind of atoms. The intensity of diffraction can be obtained from radial distribution function (RDF). Since practical observation is limited to a finite region, termination effect should be taken into consideration. Accuracy of analysis is not good in case of X-ray diffraction. The analysis by neutron diffraction is preferable. (Kato, T.)

  19. Translational and rotational diffusion of dilute solid amorphous spherical nanocolloids by molecular dynamics simulation

    Science.gov (United States)

    Heyes, D. M.; Nuevo, M. J.; Morales, J. J.

    Following on from our previous study (Heyes, D. M., Nuevo, M. J, and Morales, J. J., 1996, Molec. Phys., 88, 1503), molecular dynamics simulations have been carried out of translational and rotational diffusion of atomistically rough near-spherical solid Lennard-Jones (LJ) clusters immersed in a Weeks-Chandler-Andersen liquid solvent. A single cluster consisting of up to about 100LJ particles as part of an 8000 atom fluid system was considered in each case. The translational and rotational diffusion coefficients decrease with increasing cluster size and solvent density (roughly in proportion to the molar volume of the solvent). The simulations reveal that for clusters in excess of about 30LJ atoms there is a clear separation of timescales between angular velocity and orientation relaxation which adhere well to the small-step diffusion model encapsulated in Hubbard's relationship. For 100 atom clusters both the StokesEinstein (translation) and Stokes-Einstein-Debye (rotation) equations apply approximately. The small departures from these reference solutions indicate that the translational relaxation experiences a local viscosity in excess of the bulk value (typically by ~ 30%), whereas rotational relaxation experiences a smaller viscosity than the bulk (typically by ~ 30%) reasonably in accord with the Gierer-Wirtz model. Both of these observations are consistent with an observed layering of the liquid molecules next to the cluster observed in our previous study.

  20. Ion-reversibility studies in amorphous solids using the two-atom scattering model

    International Nuclear Information System (INIS)

    Oen, O.S.

    1981-06-01

    An analytical two-atom scattering model has been developed to treat the recent discovery of the enhancement near 180 0 of Rutherford backscattering yields from disordered solids. In contrast to conventional calculations of Rutherford backscattering that treat scattering from a single atom only (the backscattering atom), the present model includes the interaction of a second atom lying between the target surface and the backscattering plane. The projectile ion makes a glancing collision with this second atom both before and after it is backscattered. The model predicts an enhancement effect whose physical origin arises from the tolerance of path for those ions whose inward and outward trajectories lie in the vicinity of the critical impact parameter. Results using Moliere scattering show how the yield enhancement depends on ion energy, backscattering depth, exit angle, scattering potential, atomic numbers of the projectile and target, and target density. In the model the critical impact parameter and critical angle play important roles. It is shown that these quantities depend on a single dimensionless parameter and analytical expressions for them are given which are accurate to better than 1%

  1. Evaluation and modeling of the eutectic composition of various drug-polyethylene glycol solid dispersions.

    Science.gov (United States)

    Baird, Jared A; Taylor, Lynne S

    2011-06-01

    The purpose of this study was to gain a better understanding of which factors contribute to the eutectic composition of drug-polyethylene glycol (PEG) blends and to compare experimental values with predictions from the semi-empirical model developed by Lacoulonche et al. Eutectic compositions of various drug-PEG 3350 solid dispersions were predicted, assuming athermal mixing, and compared to experimentally determined eutectic points. The presence or absence of specific interactions between the drug and PEG 3350 were investigated using Fourier transform infrared (FT-IR) spectroscopy. The eutectic composition for haloperidol-PEG and loratadine-PEG solid dispersions was accurately predicted using the model, while predictions for aceclofenac-PEG and chlorpropamide-PEG were very different from those experimentally observed. Deviations in the model prediction from ideal behavior for the systems evaluated were confirmed to be due to the presence of specific interactions between the drug and polymer, as demonstrated by IR spectroscopy. Detailed analysis showed that the eutectic composition prediction from the model is interdependent on the crystal lattice energy of the drug compound (evaluated from the melting temperature and the heat of fusion) as well as the nature of the drug-polymer interactions. In conclusion, for compounds with melting points less than 200°C, the model is ideally suited for predicting the eutectic composition of systems where there is an absence of drug-polymer interactions.

  2. Dispersion Corrected Structural Properties and Quasiparticle Band Gaps of Several Organic Energetic Solids.

    Science.gov (United States)

    Appalakondaiah, S; Vaitheeswaran, G; Lebègue, S

    2015-06-18

    We have performed ab initio calculations for a series of energetic solids to explore their structural and electronic properties. To evaluate the ground state volume of these molecular solids, different dispersion correction methods were accounted in DFT, namely the Tkatchenko-Scheffler method (with and without self-consistent screening), Grimme's methods (D2, D3(BJ)), and the vdW-DF method. Our results reveal that dispersion correction methods are essential in understanding these complex structures with van der Waals interactions and hydrogen bonding. The calculated ground state volumes and bulk moduli show that the performance of each method is not unique, and therefore a careful examination is mandatory for interpreting theoretical predictions. This work also emphasizes the importance of quasiparticle calculations in predicting the band gap, which is obtained here with the GW approximation. We find that the obtained band gaps are ranging from 4 to 7 eV for the different compounds, indicating their insulating nature. In addition, we show the essential role of quasiparticle band structure calculations to correlate the gap with the energetic properties.

  3. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats.

    Science.gov (United States)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague-Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn(2+) and albumin levels (Ptaurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (PTaurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (Ptaurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Enhanced chemoprophylactic and clinical efficacy of albendazole formulated as solid dispersions in experimental cystic echinococcosis.

    Science.gov (United States)

    Pensel, Patricia E; Castro, Silvina; Allemandi, Daniel; Bruni, Sergio Sánchez; Palma, Santiago D; Elissondo, María Celina

    2014-06-16

    Cystic echinococcosis is a chronic, complex, and still neglected disease. Although albendazole has demonstrated efficacy, only about one-third of patients experience complete remission or cure and 30-50% of treated patients develop some evidence of a therapeutic response. Different strategies have been developed in order to improve the albendazole water solubility and dissolution rate. The aim of the current work was to investigate the chemoprophylactic and clinical efficacy of an albendazole:poloxamer 188 solid dispersion formulation on mice infected with Echinococcus granulosus metacestodes. Albendazole formulated as solid dispersion had greater chemoprophylactic and clinical efficacy than albendazole alone. The improved in therapeutic efficacy could be a consequence of the increase in the systemic availability of albendazole sulfoxide. The work reported here demonstrates that in vivo treatment with albendazole:poloxamer 188 impairs the development of the hydatid cysts. This new pharmacotechnically based strategy could be a suitable alternative for treating cystic echinococcosis in humans. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Better understanding of dissolution behaviour of amorphous drugs by in situ solid-state analysis using Raman spectroscopy

    DEFF Research Database (Denmark)

    Savolainen, M; Kogermann, K; Heinz, A

    2009-01-01

    of two amorphous drugs, indomethacin (IMC) and carbamazepine (CBZ). The dissolution rate was higher from amorphous IMC compared to the crystalline alpha- and gamma-forms. However, the dissolution rate started to slow down during the experiment. In situ Raman analysis verified that at that time point...

  6. Comparative study of sustained-release lipid microparticles and solid dispersions containing ibuprofen

    Directory of Open Access Journals (Sweden)

    Hugo Almeida

    2012-09-01

    Full Text Available Ibuprofen is one of the most important non-steroidal anti-inflammatory drugs used in the treatment of inflammatory diseases. In its pure state, ibuprofen presents poor physical and mechanical characteristics and its use in solid dosage forms needs the addition of excipients that improve these properties. The selection of the best excipients and the most suitable pharmaceutical dosage form to carry ibuprofen is very important for the industrial success of this drug. Given these factors, lipid microparticles and solid dispersions of ibuprofen with cetyl alcohol, stearic acid, and hydrogenated castor oil were prepared. These formulations were intended to improve the physical and mechanical characteristics and to sustain the release of this drug. Physical mixtures were also prepared with the same ingredients in similar proportions. The solid dispersions of ibuprofen/stearic acid and ibuprofen/hydrogenated castor oil showed the best flow characteristics compared with pure ibuprofen. Further, gelatin capsules filled with lipid microparticles and solid dispersions were submitted to dissolution tests in order to study the influence of the prepared systems in the release profiles of ibuprofen. Prolonged release of ibuprofen was achieved with the lipid microparticles and solid dispersions prepared with the different types of excipients.O ibuprofeno é um dos antiinflamatórios não esteróides mais utilizados no tratamento de patologias associadas a processos inflamatórios. Este fármaco, quando no seu estado puro, apresenta características físicas e mecânicas pouco satisfatórias e a sua utilização em formas sólidas só é possível se forem adicionados excipientes que permitam melhorar estas propriedades. A seleção dos excipientes ideais e da forma farmacêutica mais adequada para veicular o ibuprofeno é fundamental para o sucesso industrial deste fármaco. Tendo em conta estes fatores, prepararam-se micropartículas lipídicas e dispersões s

  7. THE MECHANISM OF SURFACE DIFFUSION OF H AND D ATOMS ON AMORPHOUS SOLID WATER: EXISTENCE OF VARIOUS POTENTIAL SITES

    Energy Technology Data Exchange (ETDEWEB)

    Hama, Tetsuya; Kuwahata, Kazuaki; Watanabe, Naoki; Kouchi, Akira; Chigai, Takeshi [Institute of Low Temperature Science, Hokkaido University, Sapporo, Hokkaido 060-0819 (Japan); Kimura, Yuki [Department of Earth and Planetary Materials Science, Tohoku University, Sendai 980-8578 (Japan); Pirronello, Valerio, E-mail: hama@lowtem.hokudai.ac.jp [Dipartimento di Fisica e Astronomia, Universita' di Catania, I-95125 Catania, Sicily (Italy)

    2012-10-01

    To understand elementary processes leading to H{sub 2} formation, and the hydrogenation and deuteration reactions of adsorbed species on dust grains in dense clouds, we experimentally investigated the diffusion of atomic hydrogen and deuterium on amorphous solid water (ASW) at temperatures of 8-15 K. The present study extended our previous study for selective detections of H and D atoms, and of H{sub 2} (J = 0 and 1) and D{sub 2} (J = 0 and 1) molecules adsorbed on ASW using both photo-stimulated desorption and resonance-enhanced multiphoton ionization, to investigate potential sites on ASW for diffusion, recombination dynamics, and the diffusion mechanism of H and D atoms. Our results demonstrate that the ASW surface contains various potential sites that can be categorized into at least three groups: very shallow, middle-, and deep-potential sites, with diffusion activation energies of {<=}18, 22 (23 meV for D atoms), and {>=}30 meV, respectively. The present study pictured the outline of H{sub 2} formation on cosmic ice dust at low temperatures: H atoms landing on the dust will diffuse rapidly at the abundant shallow and middle sites on ASW, and finally become trapped at deep sites. The H atoms that arrive next recombine with such trapped H atoms to yield H{sub 2} molecules. The small isotopic difference between the diffusion of H and D atoms on ASW indicates that the diffusion mechanism can be explained by thermal hopping, at least at middle-potential sites.

  8. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    International Nuclear Information System (INIS)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui

    2015-01-01

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn 2+ and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase + was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights:

  9. Taurine zinc solid dispersions attenuate doxorubicin-induced hepatotoxicity and cardiotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Yu; Mei, Xueting; Yuan, Jingquan; Lu, Wenping; Li, Binglong; Xu, Donghui, E-mail: Donghuixu007@163.com

    2015-11-15

    The clinical efficacy of anthracycline anti-neoplastic agents is limited by cardiac and hepatic toxicities. The aim of this study was to assess the hepatoprotective and cardioprotective effects of taurine zinc solid dispersions, which is a newly-synthesized taurine zinc compound, against doxorubicin-induced toxicity in Sprague–Dawley rats intraperitoneally injected with doxorubicin hydrochloride (3 mg/kg) three times a week (seven injections) over 28 days. Hemodynamic parameters, levels of liver toxicity markers and oxidative stress were assessed. Taurine zinc significantly attenuated the reductions in blood pressure, left ventricular pressure and ± dp/dtmax, increases in serum alanine aminotransferase and aspartate aminotransferase activities, and reductions in serum Zn{sup 2+} and albumin levels (P < 0.05 or 0.01) induced by doxorubicin. In rats treated with doxorubicin, taurine zinc dose-dependently increased liver superoxide dismutase activity and glutathione concentration, and decreased malondialdehyde level (P < 0.01). qBase{sup +} was used to evaluate the stability of eight candidate reference genes for real-time quantitative reverse-transcription PCR. Taurine zinc dose-dependently increased liver heme oxygenase-1 and UDP-glucuronyl transferase mRNA and protein expression (P < 0.01). Western blotting demonstrated that taurine zinc inhibited c-Jun N-terminal kinase phosphorylation by upregulating dual-specificity phosphoprotein phosphatase-1. Additionally, taurine zinc inhibited cardiomyocyte apoptosis as there was decreased TUNEL/DAPI positivity and protein expression of caspase-3. These results indicate that taurine zinc solid dispersions prevent the side-effects of anthracycline-based anticancer therapy. The mechanisms might be associated with the enhancement of antioxidant defense system partly through activating transcription to synthesize endogenous phase II medicine enzymes and anti-apoptosis through inhibiting JNK phosphorylation. - Highlights:

  10. Nonlinear Dispersive Elastic Waves in Solids: Exact, Approximate, and Numerical Solutions

    Science.gov (United States)

    Khajehtourian, Romik

    Wave motion lies at the heart of many disciplines in the physical sciences and engineering. For example, problems and applications involving light, sound, heat, or fluid flow are all likely to involve wave dynamics at some level. A particular class of problems is concerned with the propagation of elastic waves in a solid medium, such as a fiber-reinforced composite material responding to vibratory excitations, or soil and rock admitting seismic waves moments after the onset of an earthquake, or phonon transport in a semiconducting crystal like silicon. Regardless of the type of wave, the dispersion relation provides a fundamental characterization of the elastodynamic properties of the medium. The first part of the dissertation examines the propagation of a large-amplitude elastic wave in a one-dimensional homogeneous medium with a focus on the effects of inherent nonlinearities on the dispersion relation. Considering a thin rod, where the thickness is small compared to the wavelength, an exact, closed-form formulation is presented for the treatment of two types of nonlinearity in the strain-displacement gradient relation: Green-Lagrange and Hencky. The derived relation is then verified by direct time-domain simulations, examining both instantaneous dispersion (by direct observation) and short-term, pre-breaking dispersion (by Fourier transformation). A high-order perturbation analysis is also conducted yielding an explicit analytical space-time solution, which is shown to be spectrally accurate. The results establish a perfect match between theory and simulation and reveal that regardless of the strength of the nonlinearity, the dispersion relation fully embodies all information pertaining to the nonlinear harmonic generation mechanism that unfolds as an arbitrary-profiled wave evolves in the medium. In the second part of the dissertation, the analysis is extended to a continuous periodic thin rod exhibiting multiple phases or embedded local resonators. The

  11. A new percolation model for composite solid electrolytes and dispersed ionic conductors

    Science.gov (United States)

    Risyad Hasyim, Muhammad; Lanagan, Michael T.

    2018-02-01

    Composite solid electrolytes (CSEs) including conductor/insulator composites known as dispersed ionic conductors (DICs) have motivated the development of novel percolation models that describe their conductivity. Despite the long history, existing models lack in one or more key areas: (1) rigorous foundation for their physical theory, (2) explanation for non-universal conductor-insulator transition, (3) classification of DICs, and (4) extension to frequency-domain. This work describes a frequency-domain effective medium approximation (EMA) of a bond percolation model for CSEs. The EMA is derived entirely from Maxwell’s equations and contains basic microstructure parameters. The model was applied successfully to several composite systems from literature. Simulations and fitting of literature data address these key areas and illustrate the interplay between space charge layer properties and bulk microstructure.

  12. EVALUATION OF A BUFFERED SOLID PHASE DISPERSION PROCEDURE ADAPTED FOR PESTICIDE ANALYSES IN THE SOIL MATRIX

    Directory of Open Access Journals (Sweden)

    Ana María Domínguez

    2015-08-01

    Full Text Available An evaluation of the pesticides extracted from the soil matrix was conducted using a citrate-buffered solid phase dispersion sample preparation method (QuEChERS. The identification and quantitation of pesticide compounds was performed using gas chromatography-mass spectrometry. Because of the occurrence of the matrix effect in 87% of the analyzed pesticides, the quantification was performed using matrix-matched calibration. The method's quantification limits were between 0.01 and 0.5 mg kg-1. Repeatability and intermediate precision, expressed as a relative standard deviation percentage, were less than 20%. The recoveries in general ranged between 62% and 99%, with a relative standard deviation < 20%. All the responses were linear, with a correlation coefficient (r ≥0.99.

  13. Preparation and investigation of mefenamic acid - polyethylene glycol - sucrose ester solid dispersions.

    Science.gov (United States)

    Fülöp, Ibolya; Gyéresi, Árpád; Kiss, Lóránd; Deli, Mária A; Croitoru, Mircea Dumitru; Szabó-Révész, Piroska; Aigner, Zoltán

    2015-12-01

    Mefenamic acid (MA) is a widely used non-steroidal antiinflammatory (NSAID) drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670) and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives.

  14. Comparative study of curcumin and curcumin formulated in a solid dispersion: Evaluation of their antigenotoxic effects

    Directory of Open Access Journals (Sweden)

    Leonardo Meneghin Mendonça

    2015-01-01

    Full Text Available AbstractCurcumin (CMN is the principal active component derived from the rhizome of Curcuma longa (Curcuma longa L.. It is a liposoluble polyphenolic compound that possesses great therapeutic potential. Its clinical application is, however, limited by the low concentrations detected following oral administration. One key strategy for improving the solubility and bioavailability of poorly water-soluble drugs is solid dispersion, though it is not known whether this technique might influence the pharmacological effects of CMN. Thus, in this study, we aimed to evaluate the antioxidant and antigenotoxic effects of CMN formulated in a solid dispersion (CMN SD compared to unmodified CMN delivered to Wistar rats. Cisplatin (cDDP was used as the damage-inducing agent in these evaluations. The comet assay results showed that CMN SD was not able to reduce the formation of cDDP-DNA crosslinks, but it decreased the formation of micronuclei induced by cDDP and attenuated cDDP-induced oxidative stress. Furthermore, at a dose of 50 mg/kg b.w. both CMN SD and unmodified CMN increased the expression of Tp53 mRNA. Our results showed that CMN SD did not alter the antigenotoxic effects observed for unmodified CMN and showed effects similar to those of unmodified CMN for all of the parameters evaluated. In conclusion, CMN SD maintained the protective effects of unmodified CMN with the advantage of being chemically water soluble, with maximization of absorption in the gastrointestinal tract. Thus, the optimization of the physical and chemical properties of CMN SD may increase the potential for the therapeutic use of curcumin.

  15. Liquid-liquid and liquid-solid phase separation and flocculation for a charged colloidal dispersion

    International Nuclear Information System (INIS)

    Lai, S.K.; Wu, K.L.

    2002-01-01

    We model the intercolloidal interaction by a hard-sphere Yukawa repulsion to which is added the long-range van der Waals attraction. In comparison with the Derjaguin-Landau-Verwey-Overbeek repulsion, the Yukawa repulsion explicitly incorporates the spatial correlations between colloids and small ions. As a result, the repulsive part can be expressed analytically and has a coupling strength depending on the colloidal volume fraction. By use of this two-body potential of mean force and in conjunction with a second-order thermodynamic perturbation theory, we construct the colloidal Helmholtz free energy and use it to calculate the thermodynamic quantities, pressure and chemical potential, needed in the determination of the liquid-liquid and liquid-solid phase diagrams. We examine, in an aqueous charged colloidal dispersion, the effects of the Hamaker constant and particle size on the conformation of a stable liquid-liquid phase transition calculated with respect to the liquid-solid coexistence phases. We find that there exists a threshold Hamaker constant or particle size whose value demarcates the stable liquid-liquid coexistence phases from their metastable counterparts. Applying the same technique and using the energetic criterion, we extend our calculations to study the flocculation phenomenon in aqueous charged colloids. Here, we pay due attention to determining the loci of a stability curve stipulated for a given temperature T 0 , and obtain the parametric phase diagram of the Hamaker constant vs the coupling strength or, at given surface potential, the particle size. By imposing T 0 to be the critical temperature T c , i.e., setting k B T 0 (=k B T c ) equal to a reasonable potential barrier, we arrive at the stability curve that marks the irreversible reversible phase transition. The interesting result is that there occurs a minimum size for the colloidal particles below (above) which the colloidal dispersion is driven to an irreversible (reversible) phase

  16. Development and characterization of clay facial mask containing turmeric extract solid dispersion.

    Science.gov (United States)

    Pan-On, Suchiwa; Rujivipat, Soravoot; Ounaroon, Anan; Tiyaboonchai, Waree

    2018-04-01

    To develop clay facial mask containing turmeric extract solid dispersion (TESD) for enhancing curcumin water solubility and permeability and to determine suitable clay based facial mask. The TESD were prepared by solvent and melting solvent method with various TE to polyvinylpyrrolidone (PVP) K30 mass ratios. The physicochemical properties, water solubility, and permeability were examined. The effects of clay types on physical stability of TESD, water adsorption, and curcumin adsorption capacity were evaluated. The TESD prepared by solvent method with a TE to PVP K30 mass ratio of 1:2 showed physically stable, dry powders, when mixed with clay. When TESD was dissolved in water, the obtained TESD micelles showed spherical shape with mean size of ∼100 nm resulting in a substantial enhancement of curcumin water solubility, ∼5 mg/ml. Bentonite (Bent) and mica (M) showed the highest water adsorption capacity. The TESD's color was altered when mixed with Bent, titanium dioxide (TiO 2 ) and zinc oxide (ZnO) indicating curcumin instability. Talcum (Talc) showed the greatest curcumin adsorption followed by M and kaolin (K), respectively. Consequently, in vitro permeation studies of the TESD mixed with Talc showed lowest curcumin permeation, while TESD mixed with M or K showed similar permeation profile as free TESD solutions. The developed TESD-based clay facial mask showed lower curcumin permeation as compared to those formulations with Tween 80. The water solubility and permeability of curcumin in clay based facial mask could be improved using solid dispersion technique and suitable clay base composed of K, M, and Talc.

  17. Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol

    OpenAIRE

    Im-Sook Song; Jin-Sun Cha; Min-Koo Choi

    2016-01-01

    The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w). The solubility and dissolution rate of the curcumin solid dispersion markedly improv...

  18. Combination of (M)DSC and surface analysis to study the phase behaviour and drug distribution of ternary solid dispersions.

    Science.gov (United States)

    Meeus, Joke; Scurr, David J; Chen, Xinyong; Amssoms, Katie; Davies, Martyn C; Roberts, Clive J; Van den Mooter, Guy

    2015-04-01

    Miscibility of the different compounds that make up a solid dispersion based formulation play a crucial role in the drug release profile and physical stability of the solid dispersion as it defines the phase behaviour of the dispersion. The standard technique to obtain information on phase behaviour of a sample is (modulated) differential scanning calorimetry ((M)DSC). However, for ternary mixtures (M)DSC alone is not sufficient to characterize their phase behaviour and to gain insight into the distribution of the active pharmaceutical ingredient (API) in a two-phased polymeric matrix. MDSC was combined with complementary surface analysis techniques, specifically time-of-flight secondary ion mass spectrometry (ToF-SIMS) and atomic force microscopy (AFM). Three spray-dried model formulations with varying API/PLGA/PVP ratios were analyzed. MDSC, TOF-SIMS and AFM provided insights into differences in drug distribution via the observed surface coverage for 3 differently composed ternary solid dispersions. Combining MDSC and surface analysis rendered additional insights in the composition of mixed phases in complex systems, like ternary solid dispersions.

  19. Effect of composition in the development of carbamazepine hot-melt extruded solid dispersions by application of mixture experimental design.

    Science.gov (United States)

    Djuris, Jelena; Ioannis, Nikolakakis; Ibric, Svetlana; Djuric, Zorica; Kachrimanis, Kyriakos

    2014-02-01

    This study investigates the application of hot-melt extrusion for the formulation of carbamazepine (CBZ) solid dispersions, using polyethyleneglycol-polyvinyl caprolactam-polyvinyl acetate grafted copolymer (Soluplus, BASF, Germany) and polyoxyethylene-polyoxypropylene block copolymer (Poloxamer 407). In agreement with the current Quality by Design principle, formulations of solid dispersions were prepared according to a D-optimal mixture experimental design, and the influence of formulation composition on the properties of the dispersions (CBZ heat of fusion and release rate) was estimated. Prepared solid dispersions were characterized using differential scanning calorimetry, attenuated total reflectance infrared spectroscopy and hot stage microscopy, as well as by determination of the dissolution rate of CBZ from the hot-melt extrudates. Solid dispersions of CBZ can be successfully prepared using the novel copolymer Soluplus. Inclusion of Poloxamer 407 as a plasticizer facilitated the processing and decreased the hardness of hot-melt extrudates. Regardless of their composition, all hot-melt extrudates displayed an improvement in the release rate compared to the pure CBZ, with formulations having the ratio of CBZ : Poloxamer 407 = 1 : 1 showing the highest increase in CBZ release rate. Interactions between the mixture components (CBZ and polymers), or quadratic effects of the components, play a significant role in overall influence on the CBZ release rate. © 2013 Royal Pharmaceutical Society.

  20. Evaluation of Antibacterial Enrofloxacin in Eggs by Matrix Solid Phase Dispersion-Flow Injection Chemiluminescence

    Directory of Open Access Journals (Sweden)

    Xiaocui Duan

    2014-01-01

    Full Text Available The study based on the chemiluminescence (CL reaction of potassium ferricyanide and luminol in sodium hydroxide medium, enrofloxacin (ENRO could dramatically enhance CL intensities and incorporated with matrix solid-phase dispersion (MSPD technique (Florisil used as dispersant, dichloromethane eluted the target compounds. A simple flow injection chemiluminescence (FL-CL method with MSPD technique for determination of ENRO in eggs was described. Under optimal conditions, the CL intensities were linearly related to ENRO concentration ranging from 4.0×10-8 g.L−1 to 5.0×10-5 g.L−1, with a correlation coefficient of 0.9989 and detection limit of 5.0×10-9 g.L−1. The relative standard deviation was 3.6% at an ENRO concentration of 2.0×10-6 g.L−1. Our testing technique can help ensure food safety, and thus, protect public health.

  1. Determination of Iron Species by Combination of Solvent Assisted-Dispersive Solid Phase Extraction and Spectrophotometry

    Directory of Open Access Journals (Sweden)

    Zahra Dehghani

    2015-06-01

    Full Text Available A simple, rapid and sensitive solvent assisted-dispersive solid phase extraction method was developed for the extraction of iron(II prior to its spectrophotometric determination. The Fe(II reacted with 2,4,6-tris(2-pyridyl-1,3,5-triazine, neutralized with sodium dodecyl sulfate and extracted onto the fine particles of benzophenone which were formed upon rapid injection of a mixture of benzophenone as the sorbent and ethanol as the disperser solvent into the aqueous solution. After phase separation, the sedimented phase containing the complex was dissolved in ethanol and the analyte concentration was determined by measuring its absorption at 594 nm. Total iron was determined after the reduction of Fe(III to Fe(II with hydroxylamine hydrochloride. Under the optimized conditions, an enhancement factor of 32, the detection limit of 0.16 µg l-1, and the relative standard deviation of 1.9% (n = 6 at 20 µg l-1 concentration level of Fe(II were achieved. The method was successfully applied to the determination of iron species in water samples and total iron in infant dry formula milk, apple, rice, spinach and parsley samples.

  2. All-PM monolithic fs Yb-fiber laser, dispersion-managed with all-solid photonic bandgap fiber

    DEFF Research Database (Denmark)

    Liu, Xiaomin; Lægsgaard, Jesper; Turchinovich, Dmitry

    2009-01-01

    All-in-fiber SESAM-modelocked self-starting fiber laser is demonstrated. Cavity dispersion is managed by a spliced-in PM all-solid photonic bandgap fiber. The laser directly delivers 1.25 nJ pulses of 280 fs duration.......All-in-fiber SESAM-modelocked self-starting fiber laser is demonstrated. Cavity dispersion is managed by a spliced-in PM all-solid photonic bandgap fiber. The laser directly delivers 1.25 nJ pulses of 280 fs duration....

  3. Kinetics of crystal growth in amorphous solid and supercooled liquid TeSe20 using DTA and d.c. conductivity measurements

    International Nuclear Information System (INIS)

    Kotkata, M.F.; Mahmoud, E.A.; El-Mously, M.K.

    1979-07-01

    Curves of reaction rate versus temperature for constant heating rates (phi=1-10 0 C/min) constructed by analytical methods have been used to demonstrate the crystallization kinetics of amorphous solid TeSe 20 . The devitrification process takes place with predominance of random nucleation and one-dimensional growth, and is limited by combined switching and splitting of the chemical bonds. The mean value for the activation energy of the amorphous-crystal transformation, average E, is found to be 64 Kcal/mole. While, the quantity E calculated on the basis of d.c. conductivity changes during different isothermal crystallization (120-175 0 C) in supercooled liquid TeSe 20 , amounts to 11.5 Kcal/mole and suggests the existence of mixed chains in the liquid alloys. (author)

  4. Preparation and evaluation of carvacrol pellets based on PVP solid-dispersion by extrusion-spheronization technique

    Directory of Open Access Journals (Sweden)

    Z. Taghizadeh*

    2017-11-01

    Full Text Available Background and objectives: Carvacrol is one of the main pharmacologically active components of Thymus vulgaris essential oil which has shown several therapeutic effects. There are few works regarding the formulation of essential oils as oral solid dosage forms due to their liquid nature, stability and technical problems. The aim of this study was to combine the solid-dispersion approach and extrusion-spheronization technique to produce pellets with desirable physico-mechanical and release properties. Methods: Solid dispersion matrix (30% of carvacrol in polyvinylpyrrolidone K30 was prepared by solvent evaporation. The matrix was mixed with Avicel and lactose and granulated by water. The wet mass was transformed into pellets by extrusion-spheronization. In order to compare the solid dispersion method with the classic approaches, another pellet formulation was prepared by absorption of carvacrol on Aerosil. The pellets were characterized for size (sieve analysis, shape factors (image analysis, mechanical strength, carvacrol content, and release rate (dissolution test. Accelerated stability test of formulations was also carried out. Results: Using suitable composition of solid dispersion matrix and granulation fluid, the pellets with desirable size and shape and mechanical properties could be produced. PVP-based pellets had higher mechanical strength, slower release rate and improved content and stability. The PVP ratio showed considerable effect on release properties of the pellets. Conclusion: Overall, the results revealed the feasibility of preparing desirable pellets containing carvacrol with acceptable content, stability and release properties which can be administered as hard gelatin capsules.

  5. Amorphous Solid Water:

    DEFF Research Database (Denmark)

    Wenzel, Jack; Linderstrøm-Lang, C. U.; Rice, Stuart A.

    1975-01-01

    -like structure factor. The Fourier-transformed structure e factor yields a real space pair distribution function consistent with local tetrahedral coordination and hydrogen bonding, as in other condensed phases of water. The intramolecular OD separation is 1.00 angstrom; the lack of data for very large wave...

  6. Methods of amorphization and investigation of the amorphous state

    OpenAIRE

    EINFALT, TOMAŽ; PLANINŠEK, ODON; HROVAT, KLEMEN

    2013-01-01

    The amorphous form of pharmaceutical materials represents the most energetic solid state of a material. It provides advantages in terms of dissolution rate and bioavailability. This review presents the methods of solid-state amorphization described in literature (supercooling of liquids, milling, lyophilization, spray drying, dehydration of crystalline hydrates), with the emphasis on milling. Furthermore, we describe how amorphous state of pharmaceuticals differ depending on method of prepara...

  7. Spray freeze drying to produce a stable Delta(9)-tetrahydrocannabinol containing inulin-based solid dispersion powder suitable for inhalation

    NARCIS (Netherlands)

    van Drooge, Dirk-Jan; Hinrichs, Wouter L J; Dickhoff, Bastiaan H J; Elli, Marco N A; Visser, Marinella R; Zijlstra, Gerrit S; Frijlink, Henderik W

    2005-01-01

    The purpose of this study is to investigate whether spray freeze drying produces an inhalable solid dispersion powder in which Delta(9)-tetrahydrocannabinol (THC) is stabilised. Solutions of THC and inulin in a mixture of tertiary butanol (TBA) and water were spray freeze dried. Drug loads varied

  8. Enhanced systemic exposure of saquinavir via the concomitant use of curcumin-loaded solid dispersion in rats.

    Science.gov (United States)

    Kim, Su-A; Kim, Sung-Whan; Choi, Hoo-Kyun; Han, Hyo-Kyung

    2013-08-16

    The present study aimed to evaluate the effect of curcumin-loaded solid dispersion on the pharmacokinetics of saquinavir in rats. Solid dispersion (SD) formulation was prepared with Solutol® HS15 to improve the solubility and bioavailability of curcumin. Subsequently, its inhibition effect on P-gp mediated cellular efflux was examined by using NCI/ADR-RES cells overexpressing P-gp. Compared to the untreated curcumin, SD formulation enhanced the cellular uptake of rhodamine-123, a P-gp substrate by approximately 3 folds in NCI/ADR-RES cells. The oral and intravenous pharmacokinetics of saquinavir were also determined in rats with/without curcumin in the different formulations. Compared to the control given saquinavir alone, curcumin-loaded solid dispersion significantly (p<0.05) increased the oral exposure of saquinavir in rats, while it did not affect the intravenous pharmacokinetics of saquinavir. The AUC and Cmax of oral saquinavir increased by 3.8- and 2.7-folds, respectively in the presence of curcumin-loaded solid dispersion. In contrast, the untreated curcumin did not affect the oral pharmacokinetics of saquinavir. These results suggest that SD formulation of curcumin should be effective to improve the in vivo effectiveness of curcumin as an absorption enhancer, leading to the improved oral exposure of saquinavir. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. The influence of microscopic and macroscopic non-stoichiometry on interfacial planarity during the solid-phase epitaxial growth of amorphized GaAs

    International Nuclear Information System (INIS)

    Belay, K.B.; Ridgway, M.C.; Llewellyn, D.J.

    1996-01-01

    The influence of microscopic and macroscopic non-stoichiometry on the Solid-Phase Epitaxial Growth of GaAs has been studied. Ion implantation has been employed to produce microscopic non-stoichiometry via Ga and As implants and macroscopic non-stoichiometry via Ga or As implants. In-situ Time Resolved Reflectivity and Transmission Electron Microscopy and ex-situ Rutherford Backscattering Spectroscopy and Channeling have been used to investigate the regrowth of amorphized GaAs layers. As non-stoichiometry shifts from microscopic to macroscopic the interface loses its planar nature and subsequently gets rougher. 7 refs., 3 figs

  10. The influence of microscopic and macroscopic non-stoichiometry on interfacial planarity during the solid-phase epitaxial growth of amorphized GaAs

    Energy Technology Data Exchange (ETDEWEB)

    Belay, K.B.; Ridgway, M.C.; Llewellyn, D.J. [Australian National Univ., Canberra, ACT (Australia). Dept. of Physics

    1996-12-31

    The influence of microscopic and macroscopic non-stoichiometry on the Solid-Phase Epitaxial Growth of GaAs has been studied. Ion implantation has been employed to produce microscopic non-stoichiometry via Ga and As implants and macroscopic non-stoichiometry via Ga or As implants. In-situ Time Resolved Reflectivity and Transmission Electron Microscopy and ex-situ Rutherford Backscattering Spectroscopy and Channeling have been used to investigate the regrowth of amorphized GaAs layers. As non-stoichiometry shifts from microscopic to macroscopic the interface loses its planar nature and subsequently gets rougher. 7 refs., 3 figs.

  11. The influence of microscopic and macroscopic non-stoichiometry on interfacial planarity during the solid-phase epitaxial growth of amorphized GaAs

    Energy Technology Data Exchange (ETDEWEB)

    Belay, K B; Ridgway, M C; Llewellyn, D J [Australian National Univ., Canberra, ACT (Australia). Dept. of Physics

    1997-12-31

    The influence of microscopic and macroscopic non-stoichiometry on the Solid-Phase Epitaxial Growth of GaAs has been studied. Ion implantation has been employed to produce microscopic non-stoichiometry via Ga and As implants and macroscopic non-stoichiometry via Ga or As implants. In-situ Time Resolved Reflectivity and Transmission Electron Microscopy and ex-situ Rutherford Backscattering Spectroscopy and Channeling have been used to investigate the regrowth of amorphized GaAs layers. As non-stoichiometry shifts from microscopic to macroscopic the interface loses its planar nature and subsequently gets rougher. 7 refs., 3 figs.

  12. Bioenhanced advanced third generation solid dispersion of tadalafil: Repurposing with improved therapy in pyelonephritis

    Directory of Open Access Journals (Sweden)

    Prashant P. Mande

    2017-11-01

    Full Text Available Tadalafil (TDL a BCS-II drug is recently reported for repurposing nephroprotective effect in Pyelonephritis (PN. However, poor water solubility and dissolution rate limited oral bioavailability pose serious challenges in its therapeutic applications. We present an advanced third generation Solid Dispersion (SD of TDL comprising a polymer in combination with a Self Micro-emulsifying Composition (SMEC to achieve high drug loading, improved stability and rapid dissolution of TDL for enhancing bioavailability and efficacy in PN. TDL-SMEC-SD was coated onto rapidly disintegrating inert tablet cores which disintegrated rapidly in water to release SD as a film. TDL-SMEC-SD was evaluated for in-vivo oral bioavailability and in-vivo efficacy in lipopolysaccharide-induced PN in rats. TDL exhibited high solubility (45.6 mg/ml in the SMEC. TDL-SMEC-SD exhibited remarkably high TDL loading (45%w/w, exceptionally low contact angle (9°, rapid in-vitro release (t50 7.3 min, microemulsion formation (globule size ~100 nm in aqueous dispersion, and stability as per ICH guidelines. SEM, DSC, and XRD confirmed high physical stability. A relative bioavailability of 350% and 150% compared to TDL and TDL-SD without SMEC respectively, established the superiority of TDL-SMEC-SD. A significant reduction in serum creatinine, blood urea nitrogen and nitric oxide levels in the lipopolysaccharide-induced PN confirmed the benefit of the TDL-SMEC-SD. The advanced third generation SMEC SDs presents the possibility of platform technology for bioenhancement of poorly water soluble drugs.

  13. On the role of acidity in amorphous silica-alumina based catalysts

    NARCIS (Netherlands)

    Poduval, D.G.

    2011-01-01

    Amorphous silica-alumina (ASA) is widely used as a solid acid catalyst or as a carrier for well-dispersed metal sulfide or metal catalysts. They are often involved in hydrocracking catalyst formulations, especially so when the aim is to produce middle distillates from heavy oil fractions. With

  14. Preparation, in-vitro and in-vivo evaluation of spray-dried ternary solid dispersion of biopharmaceutics classification system class II model drug.

    Science.gov (United States)

    Paidi, Sharan K; Jena, Sunil K; Ahuja, Bhupesh K; Devasari, Naresh; Suresh, Sarasija

    2015-05-01

    The objective of this study was to investigate the impact of a novel spray-dried ternary solid dispersion (TSD) on the dissolution rate and bioavailability of a biopharmaceutics classification system (BCS) class II model drug, atorvastatin calcium trihydrate (ATC), and evaluate its in-vitro and in-vivo performance. TSD of ATC was prepared by spray-drying method employing ethanol/water solvent systems. The TSD formulations, composed of hydroxypropyl methylcellulose (HPMC E5) and nicotinamide, were optimized by rotatable central composite design. Physicochemical characterization along with dissolution, stability and pharmacokinetic study of optimized TSD was evaluated. The optimized TSD was found to be amorphous with spherical shape morphology. It exhibited a fourfold increase in dissolution rate in comparison to ATC, with a considerable enhancement in oral bioavailability (relative bioavailability of 134.11%). Physicochemical characterization and dissolution study of optimized TSD at the end of stability studies clearly indicated that the stability of optimized TSD was due to hydrogen bonding between drug and HPMC E5 and nicotinamide. This bonding remained unaffected even under stressful conditions of high temperature and humidity. The TSD exhibits a significant increase in dissolution rate, and for this reason should be useful as an efficacious tool to enhance the bioavailability of BCS class II drug molecule, ATC. © 2015 Royal Pharmaceutical Society.

  15. Solid polymer electrolyte composite membrane comprising a porous support and a solid polymer electrolyte including a dispersed reduced noble metal or noble metal oxide

    Science.gov (United States)

    Liu, Han; Mittelsteadt, Cortney K; Norman, Timothy J; Griffith, Arthur E; LaConti, Anthony B

    2015-02-24

    A solid polymer electrolyte composite membrane and method of manufacturing the same. According to one embodiment, the composite membrane comprises a thin, rigid, dimensionally-stable, non-electrically-conducting support, the support having a plurality of cylindrical, straight-through pores extending perpendicularly between opposing top and bottom surfaces of the support. The pores are unevenly distributed, with some or no pores located along the periphery and more pores located centrally. The pores are completely filled with a solid polymer electrolyte, the solid polymer electrolyte including a dispersed reduced noble metal or noble metal oxide. The solid polymer electrolyte may also be deposited over the top and/or bottom surfaces of the support.

  16. Dispersion of dielectric permittivity and magnetic properties of solid solution PZT–PFT

    Directory of Open Access Journals (Sweden)

    Skulski Ryszard

    2015-09-01

    Full Text Available In this paper we present the results of investigations into ceramic samples of solid solution (1-x(PbZr0.53Ti0.47O3- x(PbFe0.5Ta0.503 (i.e. (1-xPZT-xPFT with x = 0.25, 0.35 and 0.45. We try to find the relation between the character of dielectric dispersion at various temperatures and the composition of this solution. We also describe the magnetic properties of investigated samples. With increasing the content of PFT also mass magnetization and mass susceptibility increase (i.e. magnetic properties are more pronounced at every temperature. The temperature dependences of mass magnetization and re­ciprocal of mass susceptibility have similar runs for all the compositions. However, our magnetic investigations exhibit weak antiferromagnetic ordering instead of the ferromagnetic one at room temperature. We can also say that up to room tempera­ture any magnetic phase transition has not occurred. It may be a result of the conditions of the technological process during producing our PZT-PFT ceramics.

  17. Use of solid dispersions to increase stability of dithranol in topical formulations

    Directory of Open Access Journals (Sweden)

    Marilene Estanqueiro

    2014-09-01

    Full Text Available The present study was planned to improve the stability of dithranol using solid dispersions (SD. Two different SD at a 1:9 ratio of dithranol/excipient were prepared: one of them using glyceryl behenate as excipient and the other using a mixture of argan oil with stearic acid (1:8 ratio as excipient. Pure dithranol and SD of dithranol were incorporated in an oil-in-water cream and in a hydrophobic ointment in a drug/dermatological base ratio of 1:10. The physical and mechanical properties of semisolid formulations incorporating the pure drug and the developed SD were evaluated through rheological and textural analysis. To evaluate the stability, L*a*b* color space parameters of SD and semisolid formulations, and pH of hydrophilic formulations were determined at defined times, during one month. Each sample was stored at different conditions namely, light exposure (room temperature, high temperature exposition (37 °C (protected from light and protected from light (room temperature. Despite higher values of firmness and adhesiveness, hydrophobic ointment exhibited the best rheological features compared to the oil-in-water cream, namely a shear-thinning behavior and high thixotropy. These formulations have also presented more stability, with minor changes in L*a*b* color space parameters. The results of this study indicate that is possible to conclude that the developed SD contributed to the increased stability of dithranol.

  18. Evaluation of Intestinal Absorption and Bioavailability of a Bergenin-Phospholipid Complex Solid Dispersion in Rats.

    Science.gov (United States)

    Gao, Haoshi; Wei, Yue; Xi, Long; Sun, Yuanyuan; Zhang, Tianhong

    2018-05-01

    Bergenin (BN) is a Biopharmaceutics Classification System class IV (BCS IV) drug with poor hydrophilicity and lipophilicity and is potentially eliminated by the efflux function of P-glycoprotein (P-gp). These factors may explain its low oral bioavailability. In the present study, a BN-phospholipid complex solid dispersion (BNPC-SD) was prepared by solvent evaporation and characterized based on differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, infrared diffraction, solubility, octanol-water partition coefficient, and in vitro dissolution. To investigate how P-gp can inhibit BN absorption in vivo, the P-gp inhibitor verapamil was co-administered with BNPC-SD to Sprague Dawley rats. By in situ single-pass intestinal perfusion, the membrane permeability of BN from BNPC-SD was higher than that of BN given alone and was improved further by co-administered verapamil. A pharmacokinetics study was done in Sprague Dawley rats, with plasma BN levels estimated by high-performance liquid chromatography. C max and AUC 0 → t values for BN were significantly higher for BNPC-SD than for BN given alone and were increased further by verapamil. Thus, the relative oral bioavailability of BNPC-SD as well as BNPC-SD co-administered with verapamil was 156.33 and 202.46%, respectively, compared with the value for BN given alone. These results showed that BNPC-SD can increase the oral bioavailability of BCS IV drugs.

  19. Development and characterization of controlled release polar lipid microparticles of candesartan cilexetil by solid dispersion

    Science.gov (United States)

    Kamalakkannan, V; Puratchikody, A; Ramanathan, L

    2013-01-01

    Candesartan cilexetil (CC) is a newer class of angiotensin II receptor antagonist used for the treatment of hypertension. The solubility of the CC is very poor and its oral bioavailability is only 15%. The controlledrelease polar lipid microparticles of CC (formulations F1, F2, F3 and F4) were prepared using variable erodible lipophilic excipients like hydrogenated castor oil, stearic acid, cetostearyl alcohol and carnauba wax by fusion method. The particle sizes of polar lipid microparticles were less than 50 microns and they were irregular in shape. Drug content ranged between 98.96 ± 2.1 and 101.9 ± 1.6% were present in all the formulations. The formulation F3 showed better drug release throughout the study period in a controlled release manner. Moreover, the in vitro release showed that all the formulations were best fitted to Higuchi model. Accelerated stability studies indicated that there was no significant changes in the chemical and physical characteristics of the formulated drug product during initial and at the end of the study period. The FTIR and DSC studies showed that there was no interaction between the drug and lipophilic excipients and no polymorphic transitions in all formulations. The X-ray diffraction peak of solid dispersion indicated that the crystalline nature of CC disappeared and no new peaks could be observed, suggesting the absence of interaction between drug and excipients. PMID:24019822

  20. Norfloxacin mixed solvency based solid dispersions: An in-vitro and in-vivo investigation

    Directory of Open Access Journals (Sweden)

    Ravindra Kamble

    2017-05-01

    Full Text Available Norfloxacin (NF is a synthetic fluoro-quinolone molecule that is used for the treatment of urinary tract infections. However, due to its poor aqueous solubility, it has low oral bioavailability. The aim of the present study was to improve the aqueous solubility and dissolution profile of NF by formulating its mixed-solvency based solid dispersions (SDs. The NF-loaded SDs were prepared by a solvent evaporation technique using urea, sodium benzoate and a niacinamide hydrotropic mixture. The prepared SDs were evaluated regarding their solubility, mean particle size, in-vitro drug release and oral bioavailability. The optimized batch showed a high percentage yield of 99.04% , with a mean particle size of 132.91 μm. Optimized SDs Exhibit 96.48% drug release. The oral bioavailabilities of NF from the optimized SDs, drug alone and marketed formulation were evaluated in Wistar rats at a dose of 20.0 mg/kg. In comparison to the drug alone, approximately 6.90- and 5.0-fold increases in AUC and Cmax, respectively, were observed for NF from mixed-solvency based SDs. The superior dissolution rate due to its reduced particle size may have contributed to the increased oral bioavailability. This study demonstrated that mixed-solvency may be an alternative approach for poorly soluble drugs to improve their solubility and oral bioavailability.

  1. Dissolution and bioavailability enhancement of alpha-asarone by solid dispersions via oral administration.

    Science.gov (United States)

    Deng, Li; Wang, Yu; Gong, Tao; Sun, Xun; Zhang, Zhi-Rong

    2017-11-01

    Alpha (α)-asarone (1-propenyl-2,4,5-methoxybenzol) (ARE) has been extensively used to treat chronic obstructive pulmonary diseases (COPD), bronchial asthma, pneumonia, and epilepsy. Due to its poor solubility and bioavailability, ARE was clinically administered via intravenous injection. However, severe allergies were often reported due to the presence of solublizers in the injection formulation. In our study, we sought to explore the biopharmaceutical classification of ARE, elucidate the mechanisms behind ARE absorption, and to develop a viable formulation to improve the oral bioavailability of ARE. ARE was not a P-glycoprotein substrate, which was absorbed in the passive mode without site specificity in the gastrointestinal tract. Solid dispersions prepared using hydrophilic matrix materials such as Pluronic F68, and polyethylene glycol (PEG) of varying molecular weights (PEG4K, PEG10K, and PEG20K) were proven to significantly improve the dissolution of ARE in vitro and the oral bioavailability of ARE in rats, which represent a promising strategy for the oral administration of ARE and other BCS II compounds.

  2. Combined application of mixture experimental design and artificial neural networks in the solid dispersion development.

    Science.gov (United States)

    Medarević, Djordje P; Kleinebudde, Peter; Djuriš, Jelena; Djurić, Zorica; Ibrić, Svetlana

    2016-01-01

    This study for the first time demonstrates combined application of mixture experimental design and artificial neural networks (ANNs) in the solid dispersions (SDs) development. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs were prepared by solvent casting method to improve carbamazepine dissolution rate. The influence of the composition of prepared SDs on carbamazepine dissolution rate was evaluated using d-optimal mixture experimental design and multilayer perceptron ANNs. Physicochemical characterization proved the presence of the most stable carbamazepine polymorph III within the SD matrix. Ternary carbamazepine-Soluplus®-poloxamer 188 SDs significantly improved carbamazepine dissolution rate compared to pure drug. Models developed by ANNs and mixture experimental design well described the relationship between proportions of SD components and percentage of carbamazepine released after 10 (Q10) and 20 (Q20) min, wherein ANN model exhibit better predictability on test data set. Proportions of carbamazepine and poloxamer 188 exhibited the highest influence on carbamazepine release rate. The highest carbamazepine release rate was observed for SDs with the lowest proportions of carbamazepine and the highest proportions of poloxamer 188. ANNs and mixture experimental design can be used as powerful data modeling tools in the systematic development of SDs. Taking into account advantages and disadvantages of both techniques, their combined application should be encouraged.

  3. Preparation of milk samples for immunoassay and liquid chromatographic screening using matrix solid-phase dispersion.

    Science.gov (United States)

    Barker, S A; Long, A R

    1994-01-01

    The use of drugs to maintain the health and maximize the output of dairy cattle has made the monitoring of milk for such agents essential. Screening tests based on immunological, microbial inhibition, and bacterial receptor assays have been developed for the detection of violative levels of therapeutic substances. However, such assays are not infallible, and false positive or negative results can occur when contaminants bind receptors or compete for the binding of the target residues. Such effects may arise from dietary sources, diseases, or other variables. Thus, a violation by such a test is not definitive until further confirmation is obtained. Our laboratory has developed extraction procedures for several drugs used in dairy production. Our method uses matrix solid-phase dispersion (MSPD) to isolate drugs away from contaminants and to eliminate many possible interferences. MSPD can also be used to enhance the specificity of such assays by fractionating various classes of drugs that may cross-react. Similarly, such methods may be used for liquid chromatographic screening and confirmation of a suspect sample.

  4. Solid Dispersion of Curcumin as Polymeric Films for Bioenhancement and Improved Therapy of Rheumatoid Arthritis.

    Science.gov (United States)

    Mande, Prashant P; Bachhav, Sagar S; Devarajan, Padma V

    2016-08-01

    The aim of our study was development of advanced third generation Curcumin self microemulsifying composition solid dispersion (Cur SMEC-SD) with high drug loading, improved stability, rapid in-vitro dissolution and enhanced bioavailability for improved therapy of rheumatoid arthritis. The Cur SMEC-SD comprising polymers (KollidonVA64[KVA], Eudragits, HPMC and Soluplus) and self microemulsifying composition of surfactant:co-surfactant:oil were coated onto rapidly disintegrating inert tablet core. SDs evaluated for stability, in-vitro release and bioenhancement. Cur SMEC-SDs exhibited high Cur loading of 45% w/w and microemulsion formation with globule size (~100 nm) irrespective of polymers. Among the polymers, SD with KVA revealed exceptionally low contact angle (7°C) and rapid in-vitro release (t50%-6.45 min). No crystallization was evident as confirmed by SEM, DSC and XRD and is attributed to SMEC aided solubilization/amorphisation, and interaction of KVA with Cur seen in the FTIR spectra. Stability was confirmed as per ICH guidelines. Remarkable bioenhancement with Cur SMEC-SD was confirmed by the > four fold and a two fold compared to Cur and Cur-SD without SMEC respectively. High efficacy ~ 80% compared to Indomethacin, seen with rheumatoid arthritis (RA) induced rats coupled with no adverse toxicity. The advanced third generation Cur SMEC-SD presents a practical technological advancement and suggests Cur SMEC-SD as promising alternative for RA therapy.

  5. Preparation and investigation of mefenamic acid – polyethylene glycol – sucrose ester solid dispersions

    Directory of Open Access Journals (Sweden)

    Fülöp Ibolya

    2015-12-01

    Full Text Available Mefenamic acid (MA is a widely used non-steroidal antiinflammatory (NSAID drug. The adverse effects typical of NSAIDs are also present in the case of MA, partly due to its low water solubility. The aim of this study was to increase the water solubility of MA in order to influence its absorption and bioavailability. Solid dispersions of MA were prepared by the melting method using polyethylene glycol 6000 and different types (laurate, D-1216; palmitate, P-1670; stearate, S-1670 and amounts of sucrose esters as carriers. The X-ray diffraction results show that MA crystals were not present in the products. Dissolution tests carried out in artificial intestinal juice showed that the product containing 10 % D-1216 increased water solubility about 3 times. The apparent permeability coefficient of MA across human Caco-2 intestinal epithelial cell layers was high and, despite the difference in solubility, there was no further increase in drug penetration in the presence of the applied additives.

  6. Facile synthesis of amorphous FeOOH/MnO2 composites as screen-printed electrode materials for all-printed solid-state flexible supercapacitors

    Science.gov (United States)

    Lu, Qiang; Liu, Li; Yang, Shuanglei; Liu, Jun; Tian, Qingyong; Yao, Weijing; Xue, Qingwen; Li, Mengxiao; Wu, Wei

    2017-09-01

    More convenience and intelligence life lead by flexible/wearable electronics requires innovation and hommization of power sources. Here, amorphous FeOOH/MnO2 composite as screen-printed electrode materials for supercapacitors (SCs) is synthesized by a facile method, and solid-state flexible SCs with aesthetic design are fabricated by fully screen-printed process on different substrates, including PET, paper and textile. The amorphous FeOOH/MnO2 composite shows a high specific capacitance and a good rate capability (350.2 F g-1 at a current density of 0.5 A g-1 and 159.5 F g-1 at 20 A g-1). It also possesses 95.6% capacitance retention even after 10 000 cycles. Moreover, the all-printed solid-state flexible SC device exhibits a high area specific capacitance of 5.7 mF cm-2 and 80% capacitance retention even after 2000 cycles. It also shows high mechanical flexibility. Simultaneously, these printed SCs on different substrates in series are capable to light up a 1.9 V yellow light emitting diode (LED), even after bending and stretching.

  7. Drop Printing of Pharmaceuticals: Effect of Molecular Weight on PEG Coated-Naproxen/PEG3350 Solid Dispersions.

    Science.gov (United States)

    Hsu, Hsin-Yun; Toth, Scott; Simpson, Garth J; Harris, Michael T

    2015-12-01

    Solid dispersions have been used to enhance the bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). However, the solid state phase, compositional uniformity, and scale-up problems are issues that need to be addressed. To allow for highly controllable products, the Drop Printing (DP) technique can provide precise dosages and predictable compositional uniformity of APIs in two/three dimensional structures. In this study, DP was used to prepare naproxen (NAP)/polyethylene glycol 3350 (PEG3350) solid dispersions with PEG coatings of different molecular weights (MW). A comparison of moisture-accelerated crystallization inhibition by different PEG coatings was assessed. Scanning electron microscopy (SEM), second harmonic generation (SHG) microscopy, and differential scanning calorimetry (DSC) analysis were performed to characterize the morphology and quantify the apparent crystallinity of NAP within the solid dispersions. Thermogravimetric analysis (TGA) was employed to measure the water content within each sample. The results suggest that the moisture-accelerated crystallization inhibition capability of the PEG coatings increased with increasing MW of the PEG coating. Besides, to demonstrate the flexibility of DP technology on manufacturing formulation, multilayer tablets with different PEG serving as barrier layers were also constructed, and their dissolution behavior was examined. By applying DP and appropriate materials, it is possible to design various carrier devices used to control the release dynamics of the API.

  8. Influence of Carrier (Polymer Type and Drug-Carrier Ratio in the Development of Amorphous Dispersions for Solubility and Permeability Enhancement of Ritonavir

    Directory of Open Access Journals (Sweden)

    Vivek S. Dave

    2017-09-01

    Full Text Available The influence of the ratio of Eudragit® L100-55 or Kolliphor® P188 on the solubility, dissolution, and permeability of ritonavir was studied with a goal of preparing solid dispersions (SDs of ritonavir. SDs were formulated using solvent evaporation or lyophilization techniques, and evaluated for their physical-chemical properties. The dissolution and permeability assessments of the functionality of the SDs were carried out. The preliminary functional stability of these formulations was assessed at accelerated storage conditions for a period of six months. Ritonavir: Eudragit® L100-55 (RE, 1:3 SD showed a 36-fold higher ritonavir solubility compared to pure ritonavir. Similarly, ritonavir: Kolliphor® P188 (RP, 1:2 SD exhibited a 49-fold higher ritonavir solubility compared to pure ritonavir. Ritonavir dissolution from RE formulations increased with increasing ratios of Eudragit® L100-55, up to a ritonavir: carrier ratio of 1:3. The ritonavir dissolution from RP formulations was highest at ritonavir: Kolliphor® P188 ratio of 1:2. Dissolution efficiencies of these formulations were found to be in line with, and supported the dissolution results. The permeability of ritonavir across the biological membrane from the optimized formulations RE (1:3 and RP (1:2 were ~76 % and ~97 %, respectively; and were significantly higher compared to that of pure ritonavir (~20 %. A preliminary (six-month stability study demonstrated the functional stability of prepared solid dispersions. The present study demonstrates that ritonavir solubility, dissolution, and permeability improvement can be achieved with a careful choice of the carrier polymer, and optimizing the amount of polymer in a SD formulation.

  9. Influence of solvent composition on the miscibility and physical stability of naproxen/PVP K 25 solid dispersions prepared by cosolvent spray-drying.

    Science.gov (United States)

    Paudel, Amrit; Van den Mooter, Guy

    2012-01-01

    To investigate the influence of solvent properties on the phase behavior and physical stability of spray-dried solid dispersions containing naproxen and PVP K 25 prepared from binary cosolvent systems containing methanol, acetone and dichloromethane. The viscosity, polymer globular size and evaporation rate of the spray-drying feed solutions were characterized. The solid dispersions were prepared by spray-drying drug-polymer solutions in binary solvent blends containing different proportions of each solvent. The phase behavior was investigated with mDSC, pXRD, FT-IR and TGA. Further, physical stability of solid dispersions was assessed by analyzing after storage at 75% RH. The solid dispersions prepared from solvent/anti-solvent mixture showed better miscibility and physical stability over those prepared from the mixtures of good solvents. Thus, solid dispersions prepared from dichloromethane-acetone exhibited the best physicochemical attributes followed by those prepared from methanol-acetone. FT-IR analysis revealed differential drug-polymer interaction in solid dispersions prepared from various solvent blends, upon the exposure to elevated humidity. Spray-drying from a cocktail of good solvent and anti-solvent with narrower volatility difference produces solid dispersions with better miscibility and physical stability resulting from the simultaneous effect on the polymer conformation and better dispersivity of drug.

  10. Enhanced Dissolution of a Porous Carrier-Containing Ternary Amorphous Solid Dispersion System Prepared by a Hot Melt Method.

    Science.gov (United States)

    Hanada, Masataka; Jermain, Scott V; Williams, Robert O

    2018-01-01

    The focus of our study was to employ a solvent-free, thermal process to evaluate the use of a porous carrier in a drug-polymer-porous carrier ternary formulation containing a high drug load (e.g., ≥50% w/w). The purpose of the study was to improve the dissolution properties of the biopharmaceutical classification system class II drug, indomethacin, in the ternary formulation. The effect that the selected polymer has on properties of the formulation was studied, and the formulation characteristics of hypromellose (AF15), copovidone (VA64), and polyvinyl alcohol-polyethylene glycol graft copolymer was evaluated to understand differences in dissolution rates and drug adsorption onto the porous carrier. The ternary formulations were manufactured using a thermal technique that relied on heating and mixing, without the necessity of mechanical shear. All thermally processed granules that employed the porous carrier exhibited immediate release compared with crystalline indomethacin and physical mixtures. In addition, the ternary formulations maintained supersaturation compared with the binary formulations without polymer. The results of this study indicated that the thermally processed ternary formulations containing a porous carrier demonstrated a much improved dissolution profile in nonsink conditions. Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  11. [Pharmacokinetics and relative bioavailability of THC and THC-solid dispersion orally to mice at single dose].

    Science.gov (United States)

    Liao, Li; Hua, Hua; Zhao, Jun-Ning; Luo, Heng; Yang, An-Dong

    2014-03-01

    To establish a fast sensitive, reproducible LC-MS/MS method to study pharmacokinetic properties of THC, and compare relative bioavailability of THC and its solid dispersion in mice. 200 mice were divided randomly into two groups, and administered orally with THC and THC-solid dispersion after fasting (calculate on THC:400 mg x kg(-1)), used HPLC-MS/MS method to determine the THC concentration of each period at the following times: baseline ( predose ), 15, 30, 45 min, 1, 1.5, 2, 3, 4, 6, 24 h after dosing. Calculating the pharmacokinetic parameters according to the C-t curv, and then use the Phoenix WinNonlin software for data analysis. The calibration curves were linear over the range 9.06-972 microg x L(-1) for THC (R2 = 0.999). The limit of detection (LOD) was 0.7 microg x L(-1), respectively. The average extraction recoveries for THC was above 75%, The methodology recoveries were between 79% and 108%. The intra-day and inter-day RSD were less than 13%, the stability test showed that the plasma samples was stable under different conditions (RSD THC and THC-solid dispersion orally to mice shows as fllows: T(max), were 60 and 15 min, AUC(0-t) were 44 500.43 and 57 497.81 mg x L(-1) x min, AUC(0-infinity) were 51 226.00 and 68 031.48 mg x L(-1) x min, MRT(0-infinity) were 596.915 6, 661.747 7 min, CL(z)/F were 0.007 809 and 0.005 88 L x min(-1) x kg(-1). Compared with THC, the MRT and t1/2 of the THC-solid dispersion were all slightly extended, the t(max) was significantly reduced, AUC(0-24 h), AUC(0-infinity) and C(max) were all significantly higher, the relative bioavailability of THC-solid dispersion is 1.34 times of THC. The results of the experiment shows that the precision, accuracy, recovery and applicability were found to be adequate for the pharmacokinetic studies. After oral administration to mice, the relative bioavailability of THC-solid dispersion show significant improvement compared to THC.

  12. The dissolution enhancement of piroxicam in its physical mixtures and solid dispersion formulations using gluconolactone and glucosamine hydrochloride as potential carriers.

    Science.gov (United States)

    Al-Hamidi, Hiba; Obeidat, Wasfy M; Nokhodchi, Ali

    2015-01-01

    The solid dispersion technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs; however this is reliant on a suitable carrier and solvent being selected. The work presented explores amino sugars (d-glucosamine HCl and d-gluconolactone) as potential hydrophilic carriers to improve dissolution rate of a poorly water-soluble drug, piroxicam, from physical mixtures and solid dispersion formulations. Solid dispersions of the drug and carrier were prepared using different ratios by the conventional solvent evaporation method. Acetone was used as solvent in the preparation of solid dispersions. Physical mixtures of piroxicam and carrier were also prepared for comparison. The properties of all solid dispersions and physical mixtures were studied using a dissolution tester, Fourier transform infrared, XRD, SEM and differential scanning calorimetry. These results showed that the presence of glucosamine or gluconolactone can increase dissolution rate of piroxicam compared to pure piroxicam. Glucosamine or Gluconolactone could be used as carrier in solid dispersion formulations and physical mixtures to enhance the dissolution rate. Solid state studies showed that no significant changes occurred for piroxicam in physical mixtures and solid dispersion.

  13. Development of amorphous and nanocrystalline Al65Cu35-xZrx alloys by mechanical alloying

    International Nuclear Information System (INIS)

    Manna, I.; Chattopadhyay, P.P.; Banhart, F.; Fecht, H.J.

    2004-01-01

    Mechanical alloying of Al 65 Cu 35-x Zr x (x=5, 15 and 25 at.% Zr) elemental powder blends by planetary ball milling up to 50 h yields amorphous and/or nanocrystalline products. Microstructure of the milled product at different stages of milling has been characterized by X-ray diffraction, (XRD) high-resolution transmission electron microscopy (TEM) and energy dispersive X-ray spectroscopy (EDS). Among the different alloys synthesized by mechanical alloying, Al 65 Cu 20 Zr 15 yields a predominantly amorphous product, while the other two alloys develop a composite microstructure comprising nanocrystalline and amorphous solid solutions in Al 65 Cu 10 Zr 25 and nano-intermetallic phase/compound in Al 65 Cu 30 Zr 5 , respectively. The genesis of solid-state amorphization in Al 65 Cu 20 Zr 15 and Al 65 Cu 10 Zr 25 is investigated

  14. Structural and electronic effects of the solid-state amorphization and recrystallization of Cu--Ho thin films

    International Nuclear Information System (INIS)

    Venkert, A.; Shamir, N.; Talianker, M.; Atzmony, U.; Dariel, M.P.; Ben-Gurion University, Material Engineering, P.O. Box 653, Beer-Sheva, Israel)

    1987-01-01

    Amorphous alloys can be produced as the outcome of diffusion reaction between evaporated thin crystalline films. The Cu--Ho system is a favorable one for such a reaction to occur. The amorphization and the recrystallization of Cu--Ho multilayers has been previously observed using transmission electron microscopy. In the present study the various stages of the interdiffusion processes in this multilayer system were investigated by means of electron spectroscopy techniques. Auger electron spectroscopy depth profiling showed the evolution of the mixing process from the multilayer structure to its completion. The mixing process was accompanied by a shift without broadening of the x-ray photoelectron spectroscopy Ho 4d line. This shift is attributed to a charge transfer from the Ho ion. The lack of line broadening indicated that the mixing was completed down to the atomic level

  15. Dependence of charge transfer phenomena during solid-air two-phase flow on particle disperser

    Science.gov (United States)

    Tanoue, Ken-ichiro; Suedomi, Yuuki; Honda, Hirotaka; Furutani, Satoshi; Nishimura, Tatsuo; Masuda, Hiroaki

    2012-12-01

    An experimental investigation of the tribo-electrification of particles has been conducted during solid-air two-phase turbulent flow. The current induced in a metal plate by the impact of polymethylmethacrylate (PMMA) particles in a high-speed air flow was measured for two different plate materials. The results indicated that the contact potential difference between the particles and a stainless steel plate was positive, while for a nickel plate it was negative. These results agreed with theoretical contact charge transfer even if not only the particle size but also the kind of metal plate was changed. The specific charge of the PMMA particles during solid-air two-phase flow using an ejector, a stainless steel branch pipe, and a stainless steel straight pipe was measured using a Faraday cage. Although the charge was negative in the ejector, the particles had a positive specific charge at the outlet of the branch pipe, and this positive charge increased in the straight pipe. The charge decay along the flow direction could be reproduced by the charging and relaxation theory. However, the proportional coefficients in the theory changed with the particle size and air velocity. Therefore, an unexpected charge transfer occurred between the ejector and the branch pipe, which could not be explained solely by the contact potential difference. In the ejector, an electrical current in air might have been produced by self-discharge of particles with excess charge between the nickel diffuser in the ejector and the stainless steel nozzle or the stainless steel pipe due to a reversal in the contact potential difference between the PMMA and the stainless steel. The sign of the current depended on the particle size, possibly because the position where the particles impacted depended on their size. When dual coaxial glass pipes were used as a particle disperser, the specific charge of the PMMA particles became more positive along the particle flow direction due to the contact

  16. Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid.

    Directory of Open Access Journals (Sweden)

    Sultan Alshehri

    Full Text Available The present studies were undertaken to develop solvent-free solid dispersions (SDs for poorly soluble anti-inflammatory drugs mefenamic acid (MA and flufenamic acid (FFA in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW technique. Different carriers such as Pluronic F127® (PL, Eudragit EPO® (EPO, polyethylene glycol 4000 (PEG 4000 and Gelucire 50/13 (GLU were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC, thermogravimetric analysis (TGA, Fourier transform infra-red (FT-IR spectroscopy, powder X-ray diffraction (PXRD and scanning electron microscopy (SEM. The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h and FFA-PEG SDs (81.76% after 4 h in comparison with pure MA (68.09% after 4 h and pure FFA (55.27% after 4 h (P<0.05. These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs.

  17. Speciation analysis of mercury by dispersive solid-phase extraction coupled with capillary electrophoresis.

    Science.gov (United States)

    Li, Jinhua; Liu, Junying; Lu, Wenhui; Gao, Fangfang; Wang, Liyan; Ma, Jiping; Liu, Huitao; Liao, Chunyang; Chen, Lingxin

    2018-04-23

    A pretreatment method of dispersive solid-phase extraction (DSPE) along with back-extraction followed by CE-UV detector was developed for the determination of mercury species in water samples. Sulfhydryl-functionalized SiO 2 microspheres (SiO 2 -SH) were synthesized and used as DSPE adsorbents for selective extraction and enrichment of three organic mercury species namely ethylmercury (EtHg), methylmercury (MeHg), and phenylmercury (PhHg), along with L-cysteine (L-cys) containing hydrochloric acid as back-extraction solvent. Several main extraction parameters were systematically investigated including sample pH, amount of adsorbent, extraction and back-extraction time, volume of eluent, and concentration of hydrochloric acid. Under optimal conditions, good linearity was achieved with correlation coefficients over 0.9990, in the range of 4-200 μg/L for EtHg, and 2-200 μg/L for MeHg and PhHg. The LODs were obtained of 1.07, 0.34, and 0.24 μg/L for EtHg, MeHg, and PhHg, respectively, as well as the LOQs were 3.57, 1.13, and 0.79 μg/L, respectively, with enrichment factors ranging from 109 to 184. Recoveries were attained with tap and lake water samples in a range of 62.3-107.2%, with relative standard deviations of 3.5-10.1%. The results proved that the method of SiO 2 -SH based DSPE coupled with CE-UV was a simple, rapid, cost-effective, and eco-friendly alternative for the determination of mercury species in water samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Extraction of acetanilides in rice using ionic liquid-based matrix solid phase dispersion-solvent flotation.

    Science.gov (United States)

    Zhang, Liyuan; Wang, Changyuan; Li, Zuotong; Zhao, Changjiang; Zhang, Hanqi; Zhang, Dongjie

    2018-04-15

    Ionic liquid-based matrix solid phase dispersion-solvent flotation coupled with high performance liquid chromatography was developed for the determination of the acetanilide herbicides, including metazachlor, propanil, alachlor, propisochlor, pretilachlor, and butachlor in rice samples. Some experimental parameters, including the type of dispersant, the mass ratio of dispersant to sample, pH of sample solution, the type of extraction solvent, the type of ionic liquid, flotation time, and flow rate of N 2 were optimized. The average recoveries of the acetanilide herbicides at spiked concentrations of 50, 125, and 250 µg/kg ranged from 89.4% to 108.7%, and relative standard deviations were equal to or lower than 7.1%, the limits of quantification were in the range of 38.0 to 84.7 µg/kg. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Development and evaluation of gastroretentive raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions for gastric ulcer treatment.

    Science.gov (United States)

    Kerdsakundee, Nattha; Mahattanadul, Sirima; Wiwattanapatapee, Ruedeekorn

    2015-08-01

    Novel raft forming systems incorporating curcumin-Eudragit® EPO solid dispersions were developed to prolong the gastric residence time and provide for a controlled release therapy of curcumin to treat gastric ulcers. The solid dispersions of curcumin with Eudragit® EPO were prepared by the solvent evaporation method at various ratios to improve the solubility and the dissolution of curcumin. The optimum weight ratio of 1:5 for curcumin to Eudragit® EPO was used to incorporate into the raft forming systems. The raft forming formulations were composed of curcumin-Eudragit® EPO solid dispersions, sodium alginate as a gelling polymer and calcium carbonate for generating divalent Ca(2+) ions and carbon dioxide to form a floating raft. All formulations formed a gelled raft in 1min and sustained buoyancy on the 0.1N hydrochloric acid (pH 1.2) surface with a 60-85% release of curcumin within 8h. The curative effect on the acetic acid-induced chronic gastric ulcer in rats was determined. The curcumin raft forming formulations at 40mg/kg once daily showed a superior curative effect on the gastric ulcer in terms of the ulcer index and healing index than the standard antisecretory agent: lansoprazole (1mg/kg, twice daily) and a curcumin suspension (40mg/kg, twice daily). These studies demonstrated that the new raft forming systems containing curcumin solid dispersions are promising carriers for a stomach-specific delivery of poorly soluble lipophilic compounds. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Amorphous and Crystalline Particulates: Challenges and Perspectives in Drug Delivery.

    Science.gov (United States)

    Al-Obaidi, Hisham; Majumder, Mridul; Bari, Fiza

    2017-01-01

    Crystalline and amorphous dispersions have been the focus of academic and industrial research due to their potential role in formulating poorly water-soluble drugs. This review looks at the progress made starting with crystalline carriers in the form of eutectics moving towards more complex crystalline mixtures. It also covers using glassy polymers to maintain the drug as amorphous exhibiting higher energy and entropy. However, the amorphous form tends to recrystallize on storage, which limits the benefits of this approach. Specific interactions between the drug and the polymer may retard this spontaneous conversion of the amorphous drug. Some studies have shown that it is possible to maintain the drug in the amorphous form for extended periods of time. For the drug and the polymer to form a stable mixture they have to be miscible on a molecular basis. Another form of solid dispersions is pharmaceutical co-crystals, for which research has focused on understanding the chemistry, crystal engineering and physico-chemical properties. USFDA has issued a guidance in April 2013 suggesting that the co-crystals as a pharmaceutical product may be a reality; but just not yet! While some of the research is still oriented towards application of these carriers, understanding the mechanism by which drug-carrier miscibility occurs is also covered. Within this context is the use of thermodynamic models such as Flory-Huggins model with some examples of studies used to predict miscibility. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  1. Liquid-phase extraction coupled with metal-organic frameworks-based dispersive solid phase extraction of herbicides in peanuts.

    Science.gov (United States)

    Li, Na; Wang, Zhibing; Zhang, Liyuan; Nian, Li; Lei, Lei; Yang, Xiao; Zhang, Hanqi; Yu, Aimin

    2014-10-01

    Liquid-phase extraction coupled with metal-organic frameworks-based dispersive solid phase extraction was developed and applied to the extraction of pesticides in high fatty matrices. The herbicides were ultrasonically extracted from peanut using ethyl acetate as extraction solvent. The separation of the analytes from a large amount of co-extractive fat was achieved by dispersive solid-phase extraction using MIL-101(Cr) as sorbent. In this step, the analytes were adsorbed on MIL-101(Cr) and the fat remained in bulk. The herbicides were separated and determined by high-performance liquid chromatography. The experimental parameters, including type and volume of extraction solvent, ultrasonication time, volume of hexane and eluting solvent, amount of MIL-101(Cr) and dispersive solid phase extraction time, were optimized. The limits of detection for herbicides range from 0.98 to 1.9 μg/kg. The recoveries of the herbicides are in the range of 89.5-102.7% and relative standard deviations are equal or lower than 7.0%. The proposed method is simple, effective and suitable for treatment of the samples containing high content of fat. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs with poor water solubility.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Lee, Kyoung-Ho; Kim, Dong-Jin; Lee, Beom-Jin

    2010-05-01

    Although the solid dispersion method has been known to increase the dissolution rate of poorly water-soluble drugs by dispersing them in hydrophilic carriers, one obstacle of the solid dispersion method is its limited solubilization capacity, especially for pH-dependent soluble drugs. pH-modified solid dispersion, in which pH modifiers are incorporated, may be a useful method for increasing the dissolution rate of weakly acidic or basic drugs. Sufficient research, including the most recent reports, was undertaken in this review. How could the inclusion of the pH the pH modifiers in the solid dispersion system change drug structural behaviors, molecular interactions, microenvironmental pH, and/or release rate of pH modifiers, relating with the enhanced dissolution of weakly acidic or weakly basic drugs with poor water solubility? These questions have been investigated to determine the dissolution-modulating mechanism of pH modifiers in solid dispersion containing weakly acidic or basic drugs. It is believed that step-by-step mechanistic approaches could provide the ultimate solution for solubilizing several poorly water-soluble drugs with pH-dependent solubility from a solid dispersion system, as well as provide ideas for developing future dosage systems.

  3. Measurements of Turbulence Attenuation by a Dilute Dispersion of Solid Particles in Homogeneous Isotropic Turbulence

    Science.gov (United States)

    Eaton, John; Hwang, Wontae; Cabral, Patrick

    2002-11-01

    This research addresses turbulent gas flows laden with fine solid particles at sufficiently large mass loading that strong two-way coupling occurs. By two-way coupling we mean that the particle motion is governed largely by the flow, while the particles affect the gas-phase mean flow and the turbulence properties. Our main interest is in understanding how the particles affect the turbulence. Computational techniques have been developed which can accurately predict flows carrying particles that are much smaller than the smallest scales of turbulence. Also, advanced computational techniques and burgeoning computer resources make it feasible to fully resolve very large particles moving through turbulent flows. However, flows with particle diameters of the same order as the Kolmogorov scale of the turbulence are notoriously difficult to predict. Some simple flows show strong turbulence attenuation with reductions in the turbulent kinetic energy by up to a factor of five. On the other hand, some seemingly similar flows show almost no modification. No model has been proposed that allows prediction of when the strong attenuation will occur. Unfortunately, many technological and natural two-phase flows fall into this regime, so there is a strong need for new physical understanding and modeling capability. Our objective is to study the simplest possible turbulent particle-laden flow, namely homogeneous, isotropic turbulence with a uniform dispersion of monodisperse particles. We chose such a simple flow for two reasons. First, the simplicity allows us to probe the interaction in more detail and offers analytical simplicity in interpreting the results. Secondly, this flow can be addressed by numerical simulation, and many research groups are already working on calculating the flow. Our detailed data can help guide some of these efforts. By using microgravity, we can further simplify the flow to the case of no mean velocity for either the turbulence or the particles. In fact

  4. EXPERIMENTAL INVESTIGATION OF THE ORTHO/PARA RATIO OF NEWLY FORMED MOLECULAR HYDROGEN ON AMORPHOUS SOLID WATER

    Energy Technology Data Exchange (ETDEWEB)

    Gavilan, L.; Lemaire, J. L.; Dulieu, F.; Congiu, E.; Chaabouni, H. [LERMA, UMR 8112 du CNRS, de l' Observatoire de Paris et de l' Universite de Cergy Pontoise, 5 mail Gay Lussac, F-95000 Cergy Pontoise Cedex (France); Vidali, G. [Visiting Professor. Permanent address: Physics Department, Syracuse University, Syracuse, NY 13244-1320 (United States); Chehrouri, M. [Permanent address: LEPC Universite de Saida, BP138, ENSAR, 20002 Saida (Algeria); Fillion, J.-H., E-mail: lisseth.gavilan@obspm.fr [Permanent address: LPMAA, UMR 7092, Universite Pierre et Marie Curie, F-75252 Paris Cedex 05 (France)

    2012-11-20

    Several astronomical observations have shown that the ortho/para ratio (OPR) of H{sub 2} can differ from the expected statistical value of 3 or the local thermodynamic equilibrium (LTE) value at the gas or dust temperature. It is thus important to know the OPR of H{sub 2} newly formed on dust grain surfaces, in order to clarify the dependence of the observed OPR in space on the formation process. Using an experimental setup designed to mimic interstellar medium environments, we measured the OPR of H{sub 2} and D{sub 2} formed on the surface of porous amorphous water ice held at 10 K. We report for the first time the OPR value for newly formed D{sub 2}, consistent with the expected LTE value at the high-temperature limit found by previous theoretical and experimental works on the determination of the OPR upon H{sub 2} formation on surfaces at low temperature.

  5. EXPERIMENTAL INVESTIGATION OF THE ORTHO/PARA RATIO OF NEWLY FORMED MOLECULAR HYDROGEN ON AMORPHOUS SOLID WATER

    International Nuclear Information System (INIS)

    Gavilan, L.; Lemaire, J. L.; Dulieu, F.; Congiu, E.; Chaabouni, H.; Vidali, G.; Chehrouri, M.; Fillion, J.-H.

    2012-01-01

    Several astronomical observations have shown that the ortho/para ratio (OPR) of H 2 can differ from the expected statistical value of 3 or the local thermodynamic equilibrium (LTE) value at the gas or dust temperature. It is thus important to know the OPR of H 2 newly formed on dust grain surfaces, in order to clarify the dependence of the observed OPR in space on the formation process. Using an experimental setup designed to mimic interstellar medium environments, we measured the OPR of H 2 and D 2 formed on the surface of porous amorphous water ice held at 10 K. We report for the first time the OPR value for newly formed D 2 , consistent with the expected LTE value at the high-temperature limit found by previous theoretical and experimental works on the determination of the OPR upon H 2 formation on surfaces at low temperature.

  6. Enhanced Physical Stability of Amorphous Drug Formulations via Dry Polymer Coating.

    Science.gov (United States)

    Capece, Maxx; Davé, Rajesh

    2015-06-01

    Although amorphous solid drug formulations may be advantageous for enhancing the bioavailability of poorly soluble active pharmaceutical ingredients, they exhibit poor physical stability and undergo recrystallization. To address this limitation, this study investigates stability issues associated with amorphous solids through analysis of the crystallization behavior for acetaminophen (APAP), known as a fast crystallizer, using a modified form of the Avrami equation that kinetically models both surface and bulk crystallization. It is found that surface-enhanced crystallization, occurring faster at the free surface than in the bulk, is the major impediment to the stability of amorphous APAP. It is hypothesized that a novel use of a dry-polymer-coating process referred to as mechanical-dry-polymer-coating may be used to inhibit surface crystallization and enhance stability. The proposed process, which is examined, simultaneously mills and coats amorphous solids with polymer, while avoiding solvents or solutions, which may otherwise cause stability or crystallization issues during coating. It is shown that solid dispersions of APAP (64% loading) with a small particle size (28 μm) could be prepared and coated with the polymer, carnauba wax, in a vibratory ball mill. The resulting amorphous solid was found to have excellent stability as a result of inhibition of surface crystallization. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  7. Effervescence-assisted dispersive liquid-liquid microextraction using a solid effervescent agent as a novel dispersion technique for the analysis of fungicides in apple juice.

    Science.gov (United States)

    Jiang, Wenqing; Chen, Xiaochu; Liu, Fengmao; You, Xiangwei; Xue, Jiaying

    2014-11-01

    A novel effervescence-assisted dispersive liquid-liquid microextraction method has been developed for the determination of four fungicides in apple juice samples. In this method, a solid effervescent agent is added into samples to assist the dispersion of extraction solvent. The effervescent agent is environmentally friendly and only produces an increase in the ionic strength and a negligible variation in the pH value of the aqueous sample, which does not interfere with the extraction of the analytes. The parameters affecting the extraction efficiency were investigated including the composition of effervescent agent, effervescent agent amount, formulation of effervescent agent, adding mode of effervescent agent, type and volume of extraction solvent, and pH. Under optimized conditions, the method showed a good linearity within the range of 0.05-2 mg/L for pyrimethanil, fludioxonil, and cyprodinil, and 0.1-4 mg/L for kresoxim-methyl, with the correlation coefficients >0.998. The limits of detection for the method ranged between 0.005 and 0.01 mg/L. The recoveries of the target fungicides in apple juice samples were in the range of 72.4-110.8% with the relative standard deviations ranging from 1.2 to 6.8%. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Magnetic matrix solid phase dispersion assisted dispersive liquid liquid microextraction of ultra trace polychlorinated biphenyls in water prior to GC-ECD determination

    International Nuclear Information System (INIS)

    Diao, Chunpeng; Li, Cong; Yang, Xiao; Sun, Ailing; Liu, Renmin

    2016-01-01

    Magnetic matrix solid phase dispersion (MMSPD) assisted dispersive liquid liquid microextraction (DLLME) was applied to extract ultra traces of polychlorinated biphenyls (PCBs) from water samples prior to gas chromatography with electron capture detection. PCBs in water were adsorbed by micro particles of magnetic bamboo charcoal and then transferred into the elution solvent. PCBs in the elution solvent of the MMSPD were further concentrated into trace volume extraction solvent of the DLLME procedure. Under optimized conditions, good linearity in the range of 0.2–100 ng L"−"1 was obtained with regression coefficients (r) higher than 0.9987. Based on a signal-noise ratio of 3, the limits of detection (LODs) range from 0.05–0.1 ng L"−"1. These LODs are much lower than those of MMSPD or DLLME alone. Relative standard deviations are between 4.9–8.2 %. The method was successfully applied to the determination of PCBs in lake and river water. Relative recoveries were 85.5–117.4 % for the spiked environmental water samples. (author)

  9. Temperature sensitive molecularly imprinted microspheres for solid-phase dispersion extraction of malachite green, crystal violet and their leuko metabolites

    International Nuclear Information System (INIS)

    Tan, Lei; Chen, Kuncai; He, Rong; Peng, Rongfei; Huang, Cong

    2016-01-01

    This article demonstrates the feasibility of an alternative strategy for producing temperature sensitive molecularly imprinted microspheres (MIMs) for solid-phase dispersion extraction of malachite green, crystal violet and their leuko metabolites. Thermo-sensitive MIMs can change their structure following temperature stimulation. This allows capture and release of target molecules to be controlled by temperature. The fabrication technique provides surface molecular imprinting in acetonitrile using vinyl modified silica microspheres as solid supports, methacrylic acid and N-isopropyl acrylamide as the functional monomers, ethyleneglycol dimethacrylate as the cross-linker, and malachite green as the template. After elution of the template, the MIMs can be used for fairly group-selective solid phase dispersion extraction of malachite green, crystal violet, leucomalachite green, and leucocrystal violet from homogenized fish samples at a certain temperature. Following centrifugal separation of the microspheres, the analytes were eluted with a 95:5 mixture of acetonitrile and formic acid, and then quantified by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) with isotope internal calibration. The detection limits for malachite green, crystal violet and their metabolites typically are 30 ng·kg −1 . Positive samples were identified by UHPLC-MS/MS in the positive ionization mode with multiple reaction monitoring. The method was applied to the determination of the dyes and the respective leuko dyes in fish samples, and accuracy and precision were validated by comparative analysis of the samples by using aluminum neutral columns. (author)

  10. All-solid-state flexible supercapacitors based on highly dispersed polypyrrole nanowire and reduced graphene oxide composites.

    Science.gov (United States)

    Yu, Chenfei; Ma, Peipei; Zhou, Xi; Wang, Anqi; Qian, Tao; Wu, Shishan; Chen, Qiang

    2014-10-22

    Highly dispersed polypyrrole nanowires are decorated on reduced graphene oxide sheets using a facile in situ synthesis route. The prepared composites exhibit high dispersibility, large effective surface area, and high electric conductivity. All-solid-state flexible supercapacitors are assembled based on the prepared composites, which show excellent electrochemical performances with a specific capacitance of 434.7 F g(-1) at a current density of 1 A g(-1). The as-fabricated supercapacitor also exhibits excellent cycling stability (88.1% capacitance retention after 5000 cycles) and exceptional mechanical flexibility. In addition, outstanding power and energy densities were obtained, demonstrating the significant potential of prepared material for flexible and portable energy storage devices.

  11. The determination of solubility and diffusion coefficient for solids in liquids by an inverse measurement technique using cylinders of amorphous glucose as a model compound

    International Nuclear Information System (INIS)

    Hu, Chengyao; Huang, Pei

    2011-01-01

    The importance of sugar and sugar-containing materials is well recognized nowadays, owing to their application in industrial processes, particularly in the food, pharmaceutical and cosmetic industries. Because of the large numbers of those compounds involved and the relatively small number of solubility and/or diffusion coefficient data for each compound available, it is highly desirable to measure the solubility and/or diffusion coefficient as efficiently as possible and to be able to improve the accuracy of the methods used. In this work, a new technique was developed for the measurement of the diffusion coefficient of a stationary solid solute in a stagnant solvent which simultaneously measures solubility based on an inverse measurement problem algorithm with the real-time dissolved amount profile as a function of time. This study differs from established techniques in both the experimental method and the data analysis. The experimental method was developed in which the dissolved amount of solid solute in quiescent solvent was investigated using a continuous weighing technique. In the data analysis, the hybrid genetic algorithm is used to minimize an objective function containing a calculated and a measured dissolved amount with time. This is measured on a cylindrical sample of amorphous glucose in methanol or ethanol. The calculated dissolved amount, that is a function of the unknown physical properties of the solid solute in the solvent, is calculated by the solution of the two-dimensional nonlinear inverse natural convection problem. The estimated values of the solubility of amorphous glucose in methanol and ethanol at 293 K were respectively 32.1 g/100 g methanol and 1.48 g/100 g ethanol, in agreement with the literature values, and support the validity of the simultaneously measured diffusion coefficient. These results show the efficiency and the stability of the developed technique to simultaneously estimate the solubility and diffusion coefficient. Also

  12. Crystallization inhibitors for amorphous oxides

    International Nuclear Information System (INIS)

    Reznitskij, L.A.; Filippova, S.E.

    1993-01-01

    Data for the last 10 years, in which experimental results of studying the temperature stabilization of x-ray amorphous oxides (including R 3 Fe 5 O 12 R-rare earths, ZrO 2 , In 2 O 3 , Sc 2 O 3 ) and their solid solution are presented, are generalized. Processes of amorphous oxide crystallization with the production of simple oxides, solid solutions and chemical compounds with different polyhedral structure, are investigated. Energy and crystallochemical criteria for selecting the doping inhibitor-components stabilizing the amorphous state are ascertained, temperatures and enthalpies of amorpous oxide crystallization are determined, examination of certain provisions of iso,orphous miscibility theory is conducted

  13. A green emissive amorphous fac-Alq3 solid generated by grinding crystalline blue fac-Alq3 powder.

    Science.gov (United States)

    Bi, Hai; Chen, Dong; Li, Di; Yuan, Yang; Xia, Dandan; Zhang, Zuolun; Zhang, Hongyu; Wang, Yue

    2011-04-14

    A novel green emissive Alq(3) solid with a facial isomeric form has been obtained by grinding the typical blue luminescent fac-Alq(3) crystalline powder. This is the first report, to the best of our knowledge, that a fac-Alq(3) isomer emits green light.

  14. Anomalous dissolution behaviour of tablets prepared from sugar glass-based solid dispersions

    NARCIS (Netherlands)

    Van Drooge, D.J.; Hinrichs, W.L.J.; Frijlink, H.W.

    2004-01-01

    In this study, anomalous dissolution behaviour of tablets consisting of sugar glass dispersions was investigated. The poorly aqueous soluble diazepam was used as a lipophilic model drug. The release of diazepam and sugar carrier was determined to study the mechanisms governing dissolution behaviour.

  15. Trace and ultratrace determination of heavy metal ions by energy-dispersive X-ray fluorescence spectrometry using graphene as solid sorbent in dispersive micro solid-phase extraction

    Energy Technology Data Exchange (ETDEWEB)

    Kocot, Karina; Sitko, Rafal, E-mail: rafal.sitko@us.edu.pl

    2014-04-01

    In this paper, the adsorptive properties of graphene nanosheets were used for simultaneous preconcentration of cobalt, nickel, copper and lead ions from water samples. The developed methodology is based on dispersive micro-solid phase extraction (DMSPE) which is miniaturized and a simplified version of classical solid phase extraction technique. In proposed procedure only 200 μL of suspension containing graphene (0.2 mg), ammonium pyrrolidine dithiocarbamate (APDC) (0.8 mg) and Triton-X-100 (0.1 mg) is rapidly injected to 50 mL of water sample. Then, graphene nanosheets with adsorbed metal-APDC chelates are collected on membrane filter and measured using energy-dispersive X-ray fluorescence (EDXRF) spectrometry. The various parameters including pH, amount of APDC, sample volume, amount of Triton-X-100 and sorption time were optimized in order to obtain the best recoveries. The experiment shows that Co, Ni, Cu and Pb can be simultaneously preconcentrated at pH of 5 with high recoveries (97%, 96%, 99% and 96% for Co, Ni, Cu and Pb, respectively) and very good precision (RSDs within 2.6–3.4%). Due to the excellent enrichment factors ranging from 400 to 2500 the proposed DMSPE–EDXRF procedure offers low detection limits. For optimized measurement conditions (voltage and current of X-ray tube, primary beam filter) the detection limits are even 0.08, 0.07, 0.08 and 0.20 ng mL{sup −1} for Co, Ni, Cu and Pb, respectively. - Highlights: • Excellent detection limits using EDXRF • A new preconcentration procedure combining DMSPE and EDXRF measurement • Graphene as a promising and efficient solid sorbent in DMSPE • Simple, fast, inexpensive and environmental friendly method.

  16. Solid phase epitaxy on N-type polysilicon films formed by aluminium induced crystallization of amorphous silicon

    Energy Technology Data Exchange (ETDEWEB)

    Tuezuen, O., E-mail: Ozge.Tuzun@iness.c-strasbourg.f [InESS, UMR 7163 CNRS-UdS, 23 rue du Loess, F-67037 Strasbourg Cedex 2 (France); Slaoui, A.; Roques, S.; Focsa, A. [InESS, UMR 7163 CNRS-UdS, 23 rue du Loess, F-67037 Strasbourg Cedex 2 (France); Jomard, F.; Ballutaud, D. [GEMaC-UMR 8635 CNRS, 1 place Aristide Briand, F-92195 Meudon (France)

    2009-10-01

    In this work, undoped amorphous silicon layers were deposited on n-type AIC seed films and then annealed at different temperatures for epitaxial growth. The epitaxy was carried out using halogen lamps (rapid thermal process or RTP) or a tube conventional furnace (CTP). We investigated the morphology of the resulting 2 {mu}m thick epi-layers by means of optical microscopy. An average grain size of about 40 {mu}m is formed after 90 s annealing at 1000 {sup o}C in RTP. The stress and degree of crystallinity of the epi-layers were studied by micro-Raman Spectroscopy and UV-visible spectrometer as a function of annealing time. The presence of compressive stress is observed from the peak position which shifts from 520.0 cm{sup -1} to 521.0 cm{sup -1} and 522.3 cm{sup -1} after CTP annealing for 10 min and 90 min, respectively. It is shown that the full width at half maximum (FWHM) varies from 9.8 cm{sup -1} to 15.6 cm{sup -1}, and the magnitude of stress is changing from 325 MPa to 650 MPa. Finally, the highest crystallinity is achieved after annealing at 1000 {sup o}C for 90 min in a tube furnace exhibiting a crystalline fraction of 81.5%. X-ray diffraction technique was used to determine the preferential orientation of the poly-Si thin films formed by SPE technique on n{sup +} type AIC layer. The preferential orientation is <100> for all annealing times at 1000 {sup o}C.

  17. Fast dissolving cyclodextrin complex of piroxicam in solid dispersion part I: influence of β-CD and HPβ-CD on the dissolution rate of piroxicam.

    Science.gov (United States)

    Bouchal, F; Skiba, M; Chaffai, N; Hallouard, F; Fatmi, S; Lahiani-Skiba, M

    2015-01-30

    Sublingual drug delivery is an interesting route for drug having significant hepatic first-pass metabolism or requiring rapid pharmacological effect as for patients suffering from swallowing difficulties, nausea or vomiting. Sublingual absorption could however be limited by the kinetic of drug dissolution. This study evaluated influences of cyclodextrins (β-CD or HP-β-CD) and their different inclusion process (spray-drying or freeze-drying) on the drug dissolution kinetic of solid dispersions in poly(ethylene glycol) (PEG, Mw 6000Da) of piroxicam, used as poor hydrosoluble drug model. A secondary objective was to determine influences of drug dispersion process in PEG (evaporation or melting methods) on the drug dissolution kinetic of piroxicam. Piroxicam solid dispersions containing or not cyclodextrins were characterized by different scanning calorimetry (DSC), Thermogravometry analyser (TGA) and Fourier transform-infrared spectroscopy (FT-IR) spectroscopy. In vitro drug dissolution study of these solid dispersions was then performed. The results demonstrated the high potential and interest of solid dispersions of drug previously included in cyclodextrins for sublingual delivery of hydrophobic drugs. This study also showed the advantages of evaporation method on the melting ones during drug dispersion in PEG. Indeed, drug complexation with cyclodextrins as dispersion by melting prevented the presence in solid dispersions of drug in crystalline form which can represent up to 63%. Moreover, dispersion in PEG by evaporation method gave more porous drug delivery system than with melting methods. This allowed complete (limited at most at 80-90% with melting methods) and quick drug dissolution without rebound effect like with melting ones. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol

    Directory of Open Access Journals (Sweden)

    Im-Sook Song

    2016-10-01

    Full Text Available The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 (w/w/w. The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (Cmax and area under the plasma concentration-time curve (AUC of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation.

  19. Characterization, in Vivo and in Vitro Evaluation of Solid Dispersion of Curcumin Containing d-α-Tocopheryl Polyethylene Glycol 1000 Succinate and Mannitol.

    Science.gov (United States)

    Song, Im-Sook; Cha, Jin-Sun; Choi, Min-Koo

    2016-10-17

    The aim of this study was to prepare a solid dispersion formulation of curcumin to enhance its solubility, dissolution rate, and oral bioavailability. The formulation was prepared with d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and mannitol using solvent evaporation and freeze-drying methods, which yielded a solid dispersion composed of curcumin, TPGS, and mannitol at a ratio of 1:10:15 ( w / w / w ). The solubility and dissolution rate of the curcumin solid dispersion markedly improved compared with those of curcumin powder and a physical mixture of curcumin, TPGS, and mannitol. About 90% of the curcumin was released from the solid dispersion formulation within 10 min. After administering the formulation orally to rats, higher plasma concentrations of curcumin were observed, with increases in the maximum plasma concentration (C max ) and area under the plasma concentration-time curve (AUC) of 86- and 65-fold, respectively, compared with those of curcumin powder. The solid dispersion formulation effectively increased intestinal permeability and inhibited P-gp function. These effects increased the anti-proliferative effect of curcumin in MDA-MB-231 breast cancer cells. Moreover, 2 h incubation with curcumin powder, solid dispersion formulation, and its physical mixture resulted in differential cytotoxic effect of paclitaxel in P-gp overexpressed LLC-PK1-P-gp and MDA-MB-231 cells through the inhibition of P-gp-mediated paclitaxel efflux. In conclusion, compared with curcumin, a solid dispersion formulation of curcumin with TPGS and mannitol could be a promising option for enhancing the oral bioavailability and efficacy of curcumin through increased solubility, dissolution rate, cell permeability, and P-gp modulation.

  20. Solid dispersions, part II: new strategies in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

    Science.gov (United States)

    Bikiaris, Dimitrios N

    2011-12-01

    The absorption of poorly water-soluble drugs, when presented in the crystalline state to the gastrointestinal tract, is typically dissolution rate-limited, and according to BCS these drugs belong mainly to class II. Both dissolution kinetics and solubility are particle size dependent. Nowadays, various techniques are available to the pharmaceutical industry for dissolution rate enhancement of such drugs. Among such techniques, nanosuspensions and drug formulation in solid dispersions are those with the highest interest. This review discusses strategies undertaken over the last 10 years, which have been applied for the dissolution enhancement of poorly water-soluble drugs; such processes include melt mixing, electrospinning, microwave irradiation and the use of inorganic nanoparticles. Many problems in this field still need to be solved, mainly the use of toxic solvents, and for this reason the use of innovative new procedures and materials will increase over the coming years. Melt mixing remains extremely promising for the preparation of SDs and will probably become the most used method in the future for the preparation of solid drug dispersions.

  1. Application of film-casting technique to investigate drug-polymer miscibility in solid dispersion and hot-melt extrudate.

    Science.gov (United States)

    Parikh, Tapan; Gupta, Simerdeep Singh; Meena, Anuprabha K; Vitez, Imre; Mahajan, Nidhi; Serajuddin, Abu T M

    2015-07-01

    Determination of drug-polymer miscibility is critical for successful development of solid dispersions. This report details a practical method to predict miscibility and physical stability of drug with various polymers in solid dispersion and, especially, in melt extrudates by applying a film-casting technique. Mixtures of itraconazole (ITZ) with hydroxypropylmethylcellulose phthalate (HPMCP), Kollidon(®) VA 64, Eudragit(®) E PO, and Soluplus(®) were film-casted, exposed to 40°C/75% RH for 1 month and then analyzed using differential scanning calorimetry (DSC), powder X-ray diffractometry, and polarized light microscopy (PLM). ITZ had the highest miscibility with HPMCP, being miscible at drug to polymer ratio of 6:4 (w/w). There was a downward trend of lower miscibility with Soluplus(®) (miscible at 3:7, w/w, and a few microcrystals present at 4:6, w/w), Kollidon(®) VA 64 (2:8, w/w) and Eudragit(®) E PO (casting and hot-melt extrusion (HME) using a twin screw extruder. For ITZ-Soluplus(®) mixtures, HME at 4:6 (w/w) resulted in a single phase, whereas drug crystallization was observed at higher drug load. HME of ITZ-Kollidon(®) VA 64 mixtures also correlated well with the miscibility predicted by film casting. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  2. Transport of temperature-velocity covariance in gas-solid flow and its relation to the axial dispersion coefficient

    Science.gov (United States)

    Subramaniam, Shankar; Sun, Bo

    2015-11-01

    The presence of solid particles in a steady laminar flow generates velocity fluctuations with respect to the mean fluid velocity that are termed pseudo-turbulence. The level of these pseudo-turbulent velocity fluctuations has been characterized in statistically homogeneous fixed particle assemblies and freely evolving suspensions using particle-resolved direct numerical simulation (PR-DNS) by Mehrabadi et al. (JFM, 2015), and it is found to be a significant contribution to the total kinetic energy associated with the flow. The correlation of these velocity fluctuations with temperature (or a passive scalar) generates a flux term that appears in the transport equation for the average fluid temperature (or average scalar concentration). The magnitude of this transport of temperature-velocity covariance is quantified using PR-DNS of thermally fully developed flow past a statistically homogeneous fixed assembly of particles, and the budget of the average fluid temperature equation is presented. The relation of this transport term to the axial dispersion coefficient (Brenner, Phil. Trans. Roy. Soc. A, 1980) is established. The simulation results are then interpreted in the context of our understanding of axial dispersion in gas-solid flow. NSF CBET 1336941.

  3. Enhancement of Solubility of Lamotrigine by Solid Dispersion and Development of Orally Disintegrating Tablets Using 32 Full Factorial Design

    Directory of Open Access Journals (Sweden)

    Jatinderpal Singh

    2015-01-01

    Full Text Available Present investigation deals with the preparation and evaluation of orally disintegrating tablets (ODTs of lamotrigine using β-cyclodextrin and PVP-K30 as polymers for the preparation of solid dispersion which help in enhancement of aqueous solubility of this BCS CLASS-II drug and sodium starch glycolate (SSG and crospovidone as a superdisintegrating agent, to reduce disintegration time. The ODTs were prepared by direct compression method. Nine formulations were developed with different ratios of superdisintegrating agents. All the formulations were evaluated for disintegration time, weight variation, hardness, friability, drug content uniformity, wetting time, and in vitro drug release study. In vitro drug release study was performed using United States Pharmacopoeia (USP type 2 dissolution test apparatus employing paddle stirrer at 50 rpm using 900 mL of 0.1 N HCl maintained at 37°C ± 0.5°C as the dissolution medium. On the basis of evaluation parameters formulations were prepared using β-CD 1 : 1 solid dispersion. Then 32 full factorial design was applied using SSG and crospovidone in different ratios suggested by using design expert 8.0.7.1 and optimized formulation was prepared using amount of SSG and crospovidone as suggested by the software. The optimized formulation prepared had disintegrating time of 15 s, wetting time of 24 s, and % friability of 0.55.

  4. Application of dispersion and dose assessment models to the solid and liquid wastes facilities of Ezeiza radioactive waste management area

    International Nuclear Information System (INIS)

    Amado, Valeria A.; Lopez, Fabio O.

    2007-01-01

    This paper provides a dose assessment of the critic group from the near surface facility for solid and liquid waste, located at Ezeiza Atomic Center in Argentina (Ezeiza Radioactive Waste Management Area-AGE). The calculations were made using several approaches about source term. The activities for each radionuclide and facility were taken from the National Atomic Energy Commission's Inventory that corresponds to the first trimester of 2005. The radioactive decay of each radionuclide was considered. The work was performed in two steps. In the first step, using the Nuclide Dispersion in Phreatic Aquifer Model (DRAF), the dispersion of the contaminants into the phreatic aquifer until the discharge point at a superficial water course was considered. In the second step, the Consequences of Releases to the Environment Assessment Methodology Program (PC CREAM) was used for the study of radionuclides dispersion in superficial water course and dose calculations. The results from this paper show that, for every studied radionuclide, the doses involved are significantly lower than the values established by current regulations. On the other hand, those results put in evidence the utility of simple models in estimating the order of magnitude of expected concentrations and doses. It is important to highlight that the obtained results can be used only in the context of the suppositions that were made. (author) [es

  5. Liquid chromatography tandem mass spectrometry method using solid-phase extraction and bead-beating-assisted matrix solid-phase dispersion to quantify the fungicide tebuconazole in controlled frog exposure study: analysis of water and animal tissue

    DEFF Research Database (Denmark)

    Hansen, Martin; Poulsen, Rikke; Luong, Xuan

    2014-01-01

    and on tissue from exposed and non-exposed adult X. laevis. Using solid-phase extraction (SPE), the analytical method allows for quantification of tebuconazole at concentrations as low as 3.89 pg mL(-1) in 10 mL water samples. Using bead-beating-assisted matrix solid-phase dispersion (MSPD), it was possible...

  6. Determination of clenbuterol in bovine liver by combining matrix solid phase dispersion and molecularly imprinted solid phase extraction followed by liquid chromatography/electrospray ion trap multiple stage mass spectrometry

    NARCIS (Netherlands)

    Crescenzi, C; Bayoudh, S; Cormack, P.A G; Klein, T; Ensing, K

    2001-01-01

    Matrix solid-phase dispersion(MSPD) is a new sample pretreatment for solid samples. This technique greatly simplifies sample pretreatment but, nonetheless, the extracts often still require an extra cleanup step that is both laborious and time-consuming. The potential;of combining MSPD with

  7. Dynamic speciation analysis of atrazine in aqueous latex nanoparticle dispersions using solid phase microextraction (SPME)

    NARCIS (Netherlands)

    Benhabib, K.; Town, R.M.; Leeuwen, van H.P.

    2009-01-01

    Solid phase microextraction (SPME) is applied in the dynamic speciation analysis of the pesticide atrazine in an aqueous medium containing sorbing latex nanoparticles. It is found that the overall rate of extraction of the analyte is faster than in the absence of nanoparticles and governed by the

  8. Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation, characterization, in vitro, and in vivo study.

    Science.gov (United States)

    Deshmane, Subhash; Deshmane, Snehal; Shelke, Santosh; Biyani, Kailash

    2018-06-01

    Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD 50 ). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.

  9. Solid-phase crystallization of amorphous silicon on ZnO:Al for thin-film solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Becker, C.; Conrad, E.; Dogan, P.; Fenske, F.; Gorka, B.; Haenel, T.; Lee, K.Y.; Rau, B.; Ruske, F.; Weber, T.; Gall, S.; Rech, B. [Helmholtz-Zentrum Berlin fuer Materialien und Energie (formerly Hahn-Meitner-Institut Berlin), Kekulestr. 5, D-12489 Berlin (Germany); Berginski, M.; Huepkes, J. [Institute of Photovoltaics, Forschungszentrum Juelich GmbH, D-52425 Juelich (Germany)

    2009-06-15

    The suitability of ZnO:Al thin films for polycrystalline silicon (poly-Si) thin-film solar cell fabrication was investigated. The electrical and optical properties of 700 -nm-thick ZnO:Al films on glass were analyzed after typical annealing steps occurring during poly-Si film preparation. If the ZnO:Al layer is covered by a 30 nm thin silicon film, the initial sheet resistance of ZnO:Al drops from 4.2 to 2.2 {omega} after 22 h annealing at 600 C and only slightly increases for a 200 s heat treatment at 900 C. A thin-film solar cell concept consisting of poly-Si films on ZnO:Al coated glass is introduced. First solar cell results will be presented using absorber layers either prepared by solid-phase crystallization (SPC) or by direct deposition at 600 C. (author)

  10. The significance of the amorphous potential energy landscape for dictating glassy dynamics and driving solid-state crystallisation

    DEFF Research Database (Denmark)

    Ruggiero, Michael T; Krynski, Marcin; Kissi, Eric Ofosu

    2017-01-01

    clear experimental and computational evidence in support of a theory that proposes that the shape and structure of the potential-energy surface (PES) is the fundamental factor underlying the glass-transition processes, regardless of the frequency that experimental methods probe. Whilst this has been....... Combined, these findings provide compelling evidence that the PES landscape, and the corresponding energy barriers, are the ultimate controlling feature behind the atomic and molecular dynamics of disordered solids, regardless of the frequency at which they occur....... proposed previously, we demonstrate, using ab initio molecular-dynamics (AIMD) simulations, that it is of critical importance to carefully consider the complete PES - both the intra-molecular and inter-molecular features - in order to fully understand the entire range of atomic-dynamical processes...

  11. Amorphous nanophotonics

    CERN Document Server

    Scharf, Toralf

    2013-01-01

    This book represents the first comprehensive overview over amorphous nano-optical and nano-photonic systems. Nanophotonics is a burgeoning branch of optics that enables many applications by steering the mould of light on length scales smaller than the wavelength with devoted nanostructures. Amorphous nanophotonics exploits self-organization mechanisms based on bottom-up approaches to fabricate nanooptical systems. The resulting structures presented in the book are characterized by a deterministic unit cell with tailored geometries; but their spatial arrangement is not controlled. Instead of periodic, the structures appear either amorphous or random. The aim of this book is to discuss all aspects related to observable effects in amorphous nanophotonic material and aspects related to their design, fabrication, characterization and integration into applications. The book has an interdisciplinary nature with contributions from scientists in physics, chemistry and materials sciences and sheds light on the topic fr...

  12. Effective dispersion and crosslinking in PVA/cellulose fiber biocomposites via solid-state mechanochemistry.

    Science.gov (United States)

    Niu, Yan; Zhang, Xiaofang; He, Xu; Zhao, Jiangqi; Zhang, Wei; Lu, Canhui

    2015-01-01

    A mechanochemical approach to improve the dispersion and the degree of crosslinking between cellulose fiber and polymer matrix is presented herein to create high performance poly(vinyl alcohol) (PVA)/cellulose biocomposites in a solvent-free and catalyst-free system. During a pan-milling process, the hydrogen bonds in both cellulose and PVA were effectively broken up, and the released hydroxyl groups could react with succinic anhydride (SA) to form covalent bonds between the two components. This stress-induced chemical reaction was verified by fourier transform infrared spectroscopy. The reaction kinetics was discussed according to the conversion rate of SA during the pan-milling process. Soxhlet extraction with hot water showed that the crosslinked PVA/cellulose retained more PVA in the composites due to the homogeneous and heterogeneous crosslinking. Scanning electron microscope images indicated the dispersion and interfacial interactions between PVA and cellulose were largely improved. The resulting composites exhibited remarkably enhanced mechanical properties. The tensile strength increased from 8.8 MPa (without mechanochemical treatment) to 18.2 MPa, and elongation at break increased from 76.8 to 361.7% after the treatment. Their thermal stability was also significantly improved. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Evaluation of alternative environmentally friendly matrix solid phase dispersion solid supports for the simultaneous extraction of 15 pesticides of different chemical classes from drinking water treatment sludge.

    Science.gov (United States)

    Soares, Karina Lotz; Cerqueira, Maristela Barnes Rodrigues; Caldas, Sergiane Souza; Primel, Ednei Gilberto

    2017-09-01

    This study describes the development, optimization and validation of a method for the extraction of 15 pesticides of different chemical classes in drinking water treatment sludge (DWTS) by vortex-assisted Matrix Solid Phase Dispersion (MSPD) with determination by gas chromatography coupled to mass spectrometry. It focused on the application of alternative and different solid supports to the extraction step of the MSPD. The main parameters that influenced the extraction were studied in order to obtain better recovery responses. Recoveries ranged from 70 to 120% with RSD below 20% for all analytes. Limits of quantification (LOQ) of the method ranged from 5 to 500 μg kg -1 whereas the analytical curves showed correlation coefficients above 0.997. The method under investigation used low volume of solvent (5 mL), low sample mass (1.5 g) and low mass of chitin (0.5 g), an environmentally friendly support. It has advantages, such as speed, simplicity and low cost material, over other methods. When the method was applied, 4 out of 15 pesticides were detected in the DWTS samples in concentrations below the LOQ. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Innovative separation and preconcentration technique of coagulating homogenous dispersive micro solid phase extraction exploiting graphene oxide nanosheets

    Energy Technology Data Exchange (ETDEWEB)

    Ghazaghi, Mehri [Department of Chemistry, College of Science, Semnan University, P.O. Box: 35131-19111, Semnan (Iran, Islamic Republic of); Mousavi, Hassan Zavvar, E-mail: hzmousavi@semnan.ac.ir [Department of Chemistry, College of Science, Semnan University, P.O. Box: 35131-19111, Semnan (Iran, Islamic Republic of); Rashidi, Ali Morad [Nanotechnology Research Center, Research Institute of Petroleum Industry (RIPI), West Entrance Blvd., Olympic Village, P.O. Box: 14857-33111, Tehran (Iran, Islamic Republic of); Shirkhanloo, Hamid [Occupational and Environmental Health Research Center (OEHRC), Iranian Petroleum Industry Health Research Institute (IPIHRI), Tehran (Iran, Islamic Republic of); Rahighi, Reza [Nanotechnology Research Center, Research Institute of Petroleum Industry (RIPI), West Entrance Blvd., Olympic Village, P.O. Box: 14857-33111, Tehran (Iran, Islamic Republic of); Department of Research and Development, Sharif Ultrahigh Nanotechnologists (SUN) Company, P.O. Box: 13488-96394, Tehran (Iran, Islamic Republic of)

    2016-01-01

    A uniquely novel, fast, and facile technique is introduced for the first time in which a scant amount of graphene oxide (GO), without modification, has been utilized in dispersive mode of solid phase extraction (SPE) for an efficient yet simple separation. The proposed method of coagulating homogenous dispersive micro solid phase extraction (CHD-µSPE) is based on coagulation of homogeneous GO solution with the aid of polyetheneimine (PEI). CHD-µSPE use full adsorption capacity of GO because in this method was used GO solution obtained from synthesis process without drying step and stacking nanosheets. In optimized condition, 30 µL GO solution (7 mg mL{sup −1}), obtained in synthesis process, was injected into 1.5 mL the sample solution followed by immediate injection of 53 µL PEI solution (1 mg mL{sup −1}). After inserting PEI, GO sheets aggregate and can be readily separated by centrifugation. PEI not only cause aggregation of GO, but also form three-dimensional network of GO with easy handling in following separation steps. Lead, cadmium, and chromium were selected as model analytes and the effecting parameters including the amount of GO, concentration of PEI, sample pH, extraction time, and type of desorption solvent were investigated and optimized. The results indicate that the proposed CHD-µSPE method can be successfully applied GO in dispersive mode of SPE without effecting on good capability adsorption of GO. The novel method was applied in determination of lead, cadmium, and chromium in water, human saliva, and urine samples by electrothermal atomic absorption spectrometry. The detection limits are as low as 0.035, 0.005, and 0.012 µg L{sup −1} for Pb, Cd, and Cr respectively. The intra-day precisions (RSDs) were lower than 3.8%. CHD-µSPE method showed a good linear ranges of 0.24–15.6, 0.015–0.95 and 0.039–2.33 µg L{sup −1} for Pb, Cd and Cr respectively. Method performance was investigated by determination of mentioned

  15. Separating DDTs in edible animal fats using matrix solid-phase dispersion extraction with activated carbon filter, Toyobo-KF.

    Science.gov (United States)

    Furusawa, Naoto

    2006-09-01

    A technique is presented for the economical, routine, and quantitative analysis of contamination by dichloro-diphenyl-trichloroethanes (DDTs) [pp'-DDT, pp'-dichlorodiphenyl dichloroethylene, and pp'-dichlorodiphenyl dichloreothane in beef tallow and chicken fat samples, based on their separation using matrix solid-phase dispersion (MSPD) extraction with Toyobo-KF, an activated carbon fiber. Toyobo-KF is a newly applied MSPD sorbent, and it is followed by reversed-phase high-performance liquid chromatography (HPLC) with a photodiode array detector. The resulting analytical performance parameters [recoveries of spiked DDTs (0.1, 0.2, and 0.4 microg/g) > or = 81%, with relative standard deviations of < or = 8% (n = 5), and quantitation limits < or = 0.03 microg/g], with minimal handling and cost-efficiency, indicate that the present MSPD-HPLC method may be a useful tool for routine monitoring of DDT contamination in meat.

  16. Matrix solid-phase dispersion coupled with homogeneous ionic liquid microextraction for the determination of sulfonamides in animal tissues using high-performance liquid chromatography.

    Science.gov (United States)

    Wang, Zhibing; He, Mengyu; Jiang, Chunzhu; Zhang, Fengqing; Du, Shanshan; Feng, Wennan; Zhang, Hanqi

    2015-12-01

    Matrix solid-phase dispersion coupled with homogeneous ionic liquid microextraction was developed and applied to the extraction of some sulfonamides, including sulfamerazine, sulfamethazine, sulfathiazole, sulfachloropyridazine, sulfadoxine, sulfisoxazole, and sulfaphenazole, in animal tissues. High-performance liquid chromatography was applied to the separation and determination of the target analytes. The solid sample was directly treated by matrix solid-phase dispersion and the eluate obtained was treated by homogeneous ionic liquid microextraction. The ionic liquid was used as the extraction solvent in this method, which may result in the improvement of the recoveries of the target analytes. To avoid using organic solvent and reduce environmental pollution, water was used as the elution solvent of matrix solid-phase dispersion. The effects of the experimental parameters on recoveries, including the type and volume of ionic liquid, type of dispersant, ratio of sample to dispersant, pH value of elution solvent, volume of elution solvent, amount of salt in eluate, amount of ion-pairing agent (NH4 PF6 ), and centrifuging time, were evaluated. When the present method was applied to the analysis of animal tissues, the recoveries of the analytes ranged from 85.4 to 118.0%, and the relative standard deviations were lower than 9.30%. The detection limits for the analytes were 4.3-13.4 μg/kg. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Simultaneous determination of phenolic compounds in Equisetum palustre L. by ultra high performance liquid chromatography with tandem mass spectrometry combined with matrix solid-phase dispersion extraction.

    Science.gov (United States)

    Wei, Zuofu; Pan, Youzhi; Li, Lu; Huang, Yuyang; Qi, Xiaolin; Luo, Meng; Zu, Yuangang; Fu, Yujie

    2014-11-01

    A method based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with tandem mass spectrometry is presented for the extraction and determination of phenolic compounds in Equisetum palustre. This method combines the high efficiency of matrix solid-phase dispersion extraction and the rapidity, sensitivity, and accuracy of ultra high performance liquid chromatography with tandem mass spectrometry. The influential parameters of the matrix solid-phase dispersion extraction were investigated and optimized. The optimized conditions were as follows: silica gel was selected as dispersing sorbent, the ratio of silica gel to sample was selected to be 2:1 (400/200 mg), and 8 mL of 80% methanol was used as elution solvent. Furthermore, a fast and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the determination of nine phenolic compounds in E. palustre. This method was carried out within <6 min, and exhibited satisfactory linearity, precision, and recovery. Compared with ultrasound-assisted extraction, the proposed matrix solid-phase dispersion procedure possessed higher extraction efficiency, and was more convenient and time saving with reduced requirements on sample and solvent amounts. All these results suggest that the developed method represents an excellent alternative for the extraction and determination of active components in plant matrices. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. Determination of Parabens by Injection-Port Derivatization Coupled With Gas-Chromatography-Mass Spectrometry and Matrix Solid Phase Dispersion

    Science.gov (United States)

    Djatmika, Rosalina; Ding, Wang-Hsien; Sulistyarti, Hermin

    2018-01-01

    A rapid determination of four parabens preservatives (methyl paraben, ethyl paraben, propyl paraben, and butyl paraben) in marketed seafood is presented. Analytes were extracted and purified using matrix solid-phase dispersion (MSPD) method, followed by Injection port acylation gas chromatography-mass spectrometry (GC-MS) with acetic anhydride reagent. In this method, acylation of parabens was performed by acetic anhydride at GC injection-port generating reduction of the time-consuming sample-processing steps, and the amount of toxic reagents and solvents. The parameters affecting this method such as injection port temperature, purge-off time and acylation (acetic anhydride) volume were studied. In addition, the MSPD influence factors (including the amount of dispersant and clean-up co-sorbent, as well as the volume of elution solvent) were also investigated. After MSPD method and Injection port acylation applied, good linearity of analytes was achieved. The limits of quantitation (LOQs) were 0.2 to 1.0 ng/g (dry weight). Compared with offline derivatization commonly performed, injection port acylation employs a rapid, simple, low-cost and environmental-friendly derivatization process. The optimized method has been successfully applied for the analysis of parabens in four kind of marketed seafood. Preliminary results showed that the total concentrations of four selected parabens ranged from 16.7 to 44.7 ng/g (dry weight).

  19. Iron oxide functionalized graphene nano-composite for dispersive solid phase extraction of chemical warfare agents from aqueous samples.

    Science.gov (United States)

    Chinthakindi, Sridhar; Purohit, Ajay; Singh, Varoon; Tak, Vijay; Goud, D Raghavender; Dubey, D K; Pardasani, Deepak

    2015-05-15

    Present study deals with the preparation and evaluation of graphene based magnetic nano-composite for dispersive solid phase extraction of Chemical Weapons Convention (CWC) relevant chemicals from aqueous samples. Nano-composite, Fe3O4@SiO2-G was synthesized by covalently bonding silica coated Fe3O4 onto the graphene sheets. Nerve agents (NA), Sulfur mustard (SM) and their non-toxic environmental markers were the target analytes. Extraction parameters like amount of sorbent, extraction time and desorption conditions were optimized. Dispersion of 20 milligram of sorbent in 200mL of water sample for 20min. followed by methanol/chloroform extraction produced average to good recoveries (27-94%) of targeted analytes. Recoveries of real agents exhibited great dependency upon sample pH and ionic strength. Sarin produced maximum recovery under mild acidic conditions (56% at pH 5) while VX demanded alkaline media (83% at pH 9). Salts presence in the aqueous samples was found to be advantageous, raising the recoveries to as high as 94% for SM. Excellent limits of detection (LOD) for sulphur mustard and VX (0.11ngmL(-1) and 0.19ngmL(-1) respectively) proved the utility of the developed method for the off-site analysis of CWC relevant chemicals. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Development of matrix solid-phase dispersion method for the extraction of short-chain chlorinated paraffins in human placenta.

    Science.gov (United States)

    Wang, Ying; Gao, Wei; Wu, Jing; Liu, Huijin; Wang, Yingjun; Wang, Yawei; Jiang, Guibin

    2017-12-01

    Chlorinated paraffins (SCCPs) are widely used worldwide, and they can be released into the environment during their production, transport, usage and disposal, which pose potential risks for human health. In this work, an efficient, reliable and rapid pretreatment method based on matrix solid-phase dispersion (MSPD) was developed for the analysis of short-chain CPs (SCCPs) in human placenta by gas chromatograph-electron capture negative ion low-resolution mass spectrometry (GC-ECNI-LRMS) and gas chromatography-quadrupole time-of-flight mass spectrometry (GC-QTOF-HRMS). The MSPD-relevant parameters including dispersing sorbent, sample-to-sorbent mass ratio, and elution solvent were optimized using the orthogonal test. Silica gel was found to be the optimal dispersing sorbent among the selected matrices. Under the optimal conditions, 44% acidic silica gel can be used as the co-sorbent to remove lipid and eluted by the mixture of hexane and dichloromethane (7:3, V/V). The spiked recoveries of the optimized method were 77.4% and 91.4% for analyzing SCCPs in human placenta by GC-ECNI-LRMS and GC-QTOF-HRMS, and the corresponding relative standard deviations were 10.2% and 5.6%, respectively. The method detection limit for the total SCCPs was 36.8ng/g (dry weight, dw) and 19.2ng/g (dw) as measured by GC-ECNI-LRMS and GC-QTOF-HRMS, respectively. The concentrations of SCCPs in four human placentas were in the range of

  1. Innovative separation and preconcentration technique of coagulating homogenous dispersive micro solid phase extraction exploiting graphene oxide nanosheets.

    Science.gov (United States)

    Ghazaghi, Mehri; Mousavi, Hassan Zavvar; Rashidi, Ali Morad; Shirkhanloo, Hamid; Rahighi, Reza

    2016-01-01

    A uniquely novel, fast, and facile technique is introduced for the first time in which a scant amount of graphene oxide (GO), without modification, has been utilized in dispersive mode of solid phase extraction (SPE) for an efficient yet simple separation. The proposed method of coagulating homogenous dispersive micro solid phase extraction (CHD-µSPE) is based on coagulation of homogeneous GO solution with the aid of polyetheneimine (PEI). CHD-µSPE use full adsorption capacity of GO because in this method was used GO solution obtained from synthesis process without drying step and stacking nanosheets. In optimized condition, 30 µL GO solution (7 mg mL(-1)), obtained in synthesis process, was injected into 1.5 mL the sample solution followed by immediate injection of 53 µL PEI solution (1 mg mL(-1)). After inserting PEI, GO sheets aggregate and can be readily separated by centrifugation. PEI not only cause aggregation of GO, but also form three-dimensional network of GO with easy handling in following separation steps. Lead, cadmium, and chromium were selected as model analytes and the effecting parameters including the amount of GO, concentration of PEI, sample pH, extraction time, and type of desorption solvent were investigated and optimized. The results indicate that the proposed CHD-µSPE method can be successfully applied GO in dispersive mode of SPE without effecting on good capability adsorption of GO. The novel method was applied in determination of lead, cadmium, and chromium in water, human saliva, and urine samples by electrothermal atomic absorption spectrometry. The detection limits are as low as 0.035, 0.005, and 0.012 µg L(-1) for Pb, Cd, and Cr respectively. The intra-day precisions (RSDs) were lower than 3.8%. CHD-µSPE method showed a good linear ranges of 0.24-15.6, 0.015-0.95 and 0.039-2.33 µg L(-1) for Pb, Cd and Cr respectively. Method performance was investigated by determination of mentioned metal ions in river water, human urine and

  2. Efficient sample preparation method based on solvent-assisted dispersive solid-phase extraction for the trace detection of butachlor in urine and waste water samples.

    Science.gov (United States)

    Aladaghlo, Zolfaghar; Fakhari, Alireza; Behbahani, Mohammad

    2016-10-01

    In this work, an efficient sample preparation method termed solvent-assisted dispersive solid-phase extraction was applied. The used sample preparation method was based on the dispersion of the sorbent (benzophenone) into the aqueous sample to maximize the interaction surface. In this approach, the dispersion of the sorbent at a very low milligram level was achieved by inserting a solution of the sorbent and disperser solvent into the aqueous sample. The cloudy solution created from the dispersion of the sorbent in the bulk aqueous sample. After pre-concentration of the butachlor, the cloudy solution was centrifuged and butachlor in the sediment phase dissolved in ethanol and determined by gas chromatography with flame ionization detection. Under the optimized conditions (solution pH = 7.0, sorbent: benzophenone, 2%, disperser solvent: ethanol, 500 μL, centrifuged at 4000 rpm for 3 min), the method detection limit for butachlor was 2, 3 and 3 μg/L for distilled water, waste water, and urine sample, respectively. Furthermore, the preconcentration factor was 198.8, 175.0, and 174.2 in distilled water, waste water, and urine sample, respectively. Solvent-assisted dispersive solid-phase extraction was successfully used for the trace monitoring of butachlor in urine and waste water samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Solid state welding processes for an oxide dispersion strengthened nickel-chromium-aluminum alloy

    Science.gov (United States)

    Moore, T. J.

    1975-01-01

    Solid-state welding processes were evaluated for joining TD-NiCrAl (Ni-16Cr-4Al-2ThO2) alloy sheet. Both hot-press and resistance spot welding techniques were successfully applied in terms of achieving grain growth across the bond line. Less success was achieved with a resistance seam welding process. In stress-rupture shear and tensile shear tests of lap joints at 1100 C, most failures occurred in the parent material, which indicates that the weld quality was good and that the welds were not a plane of weakness. The overall weld quality was not as good as previously attained with TD-NiCr, probably because the presence of alumina at the faying surfaces and the developmental TD-NiCrAl sheet, which was not of the quality of the TD-NiCr sheet in terms of surface flatness and dimensional control.

  4. Dispersing Si{sub 3}N{sub 4} at high solids loading - applied to protein forming

    Energy Technology Data Exchange (ETDEWEB)

    Lyckfeldt, O.; Palmqvist, L. [Swedish Ceramic Inst., Goeteborg (Sweden); Poeydemenge, F. [ENSCI, Limoges (France)

    2002-07-01

    The dispersing of a Si{sub 3}N{sub 4} powder (UBE SN-E10) at high solids loading in aqueous media was investigated. The powder was used in the as-received (raw) state, after thermal (calcinations) and/or mechanical pre-treatments (ball milling{yields}freeze granulation{yields}freeze-drying). Slips were prepared using pH adjustment with NH{sub 4}OH or an addition of Tiron (low-M{sub w} sulphonic acid). Zeta potential measurements of diluted systems and rheological evaluations of concentrated suspensions were conducted. The effect of adding whey protein concentrate (WPC) was also studied. Zeta potential measurements showed a clear decrease in pH{sub iep} by calcination, whereas Tiron slightly increased the pH{sub iep} of calcined powder and decreased the pH{sub iep} of the as-received powder. Rheological data showed that pH adjustment to 10 was more efficient in stabilising the as-received powder than the calcined powder. pH adjustment was also considered to be the most important effect of adding small amounts of Tiron (0.08 wt%). However, for calcined powder, Tiron was shown to be equally efficient as pH adjustment. Pre-milling followed by freeze granulation/freeze-drying resulted in de-agglomerated powders with improved ability to rapidly disperse and, hence, extend the possibility of achieving extreme solids loadings. When approaching the practical limits in solids loading of these pre-milled powders, slips with 49.5 vol% of as-received and 46.6 vol% of calcined powders displayed clear shear thickening behaviour. However, addition of WPC (12 wt% based on water) significantly decreased the degree of shear thickening although the viscosity at lower shear rates increased. The gelling of WPC was distinct and rapid in suspensions with the two pre-milled powders, as-received stabilised at pH 10 and calcined stabilised with Tiron. (orig.)

  5. Rational Design of a Water-Storable Hierarchical Architecture Decorated with Amorphous Barium Oxide and Nickel Nanoparticles as a Solid Oxide Fuel Cell Anode with Excellent Sulfur Tolerance.

    Science.gov (United States)

    Song, Yufei; Wang, Wei; Ge, Lei; Xu, Xiaomin; Zhang, Zhenbao; Julião, Paulo Sérgio Barros; Zhou, Wei; Shao, Zongping

    2017-11-01

    Solid oxide fuel cells (SOFCs), which can directly convert chemical energy stored in fuels into electric power, represent a useful technology for a more sustainable future. They are particularly attractive given that they can be easily integrated into the currently available fossil fuel infrastructure to realize an ideal clean energy system. However, the widespread use of the SOFC technology is hindered by sulfur poisoning at the anode caused by the sulfur impurities in fossil fuels. Therefore, improving the sulfur tolerance of the anode is critical for developing SOFCs for use with fossil fuels. Herein, a novel, highly active, sulfur-tolerant anode for intermediate-temperature SOFCs is prepared via a facile impregnation and limited reaction protocol. During synthesis, Ni nanoparticles, water-storable BaZr 0.4 Ce 0.4 Y 0.2 O 3- δ (BZCY) perovskite, and amorphous BaO are formed in situ and deposited on the surface of a Sm 0.2 Ce 0.8 O 1.9 (SDC) scaffold. More specifically, a porous SDC scaffold is impregnated with a well-designed proton-conducting perovskite oxide liquid precursor with the nominal composition of Ba(Zr 0.4 Ce 0.4 Y 0.2 ) 0.8 Ni 0.2 O 3- δ (BZCYN), calcined and reduced in hydrogen. The as-synthesized hierarchical architecture exhibits high H 2 electro-oxidation activity, excellent operational stability, superior sulfur tolerance, and good thermal cyclability. This work demonstrates the potential of combining nanocatalysts and water-storable materials in advanced electrocatalysts for SOFCs.

  6. Time-resolved shock compression of porous rutile: Wave dispersion in porous solids

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, M.U.; Graham, R.A.; Holman, G.T.

    1993-08-01

    Rutile (TiO{sub 2}) samples at 60% of solid density have been shock-loaded from 0.21 to 6.1 GPa with sample thickness of 4 mm and studied with the PVDF piezoelectric polymer stress-rate gauge. The technique uses a copper capsule to contain the sample which has PVDF gauge packages in direct contact with front and rear surfaces. A precise measure is made of the compressive stress wave velocity through the sample, as well as the input and propagated shock stress. Initial density is known from sample preparation, and the amount of shock-compression is calculated from the measurement of shock velocity and input stress. Shock states and re-shock states are measured. Observed data are consistent with previously published high pressure data. It is observed that rutile has a ``crush strength`` near 6 GPa. Propagated stress-pulse rise times vary from 234 to 916 nsec. Propagated stress-pulse rise times of shock-compressed HMX, 2Al + Fe{sub 2}O{sub 3}, 3Ni + Al, and 5Ti + 3Si are presented.

  7. Sensitive determination of three aconitum alkaloids and their metabolites in human plasma by matrix solid-phase dispersion with vortex-assisted dispersive liquid-liquid microextraction and HPLC with diode array detection.

    Science.gov (United States)

    Wang, Xiaozhong; Li, Xuwen; Li, Lanjie; Li, Min; Liu, Ying; Wu, Qian; Li, Peng; Jin, Yongri

    2016-05-01

    A simple and sensitive method for determination of three aconitum alkaloids and their metabolites in human plasma was developed using matrix solid-phase dispersion combined with vortex-assisted dispersive liquid-liquid microextraction and high-performance liquid chromatography with diode array detection. The plasma sample was directly purified by matrix solid-phase dispersion and the eluate obtained was concentrated and further clarified by vortex-assisted dispersive liquid-liquid microextraction. Some important parameters affecting the extraction efficiency, such as type and amount of dispersing sorbent, type and volume of elution solvent, type and volume of extraction solvent, salt concentration as well as sample solution pH, were investigated in detail. Under optimal conditions, the proposed method has good repeatability and reproducibility with intraday and interday relative standard deviations lower than 5.44 and 5.75%, respectively. The recoveries of the aconitum alkaloids ranged from 73.81 to 101.82%, and the detection limits were achieved within the range of 1.6-2.1 ng/mL. The proposed method offered the advantages of good applicability, sensitivity, simplicity, and feasibility, which makes it suitable for the determination of trace amounts of aconitum alkaloids in human plasma samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Dispersive solid-phase extraction followed by vortex-assisted dispersive liquid-liquid microextraction based on the solidification of a floating organic droplet for the determination of benzoylurea insecticides in soil and sewage sludge.

    Science.gov (United States)

    Peng, Guilong; He, Qiang; Mmereki, Daniel; Lu, Ying; Zhong, Zhihui; Liu, Hanyang; Pan, Weiliang; Zhou, Guangming; Chen, Junhua

    2016-04-01

    A novel dispersive solid-phase extraction combined with vortex-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet was developed for the determination of eight benzoylurea insecticides in soil and sewage sludge samples before high-performance liquid chromatography with ultraviolet detection. The analytes were first extracted from the soil and sludge samples into acetone under optimized pretreatment conditions. Clean-up of the extract was conducted by dispersive solid-phase extraction using activated carbon as the sorbent. The vortex-assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet procedure was performed by using 1-undecanol with lower density than water as the extraction solvent, and the acetone contained in the solution also acted as dispersive solvent. Under the optimum conditions, the linearity of the method was in the range 2-500 ng/g with correlation coefficients (r) of 0.9993-0.9999. The limits of detection were in the range of 0.08-0.56 ng/g. The relative standard deviations varied from 2.16 to 6.26% (n = 5). The enrichment factors ranged from 104 to 118. The extraction recoveries ranged from 81.05 to 97.82% for all of the analytes. The good performance has demonstrated that the proposed methodology has a strong potential for application in the multiresidue analysis of complex matrices. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Preparation and evaluation of azithromycin binary solid dispersions using various polyethylene glycols for the improvement of the drug solubility and dissolution rate

    Directory of Open Access Journals (Sweden)

    Ehsan Adeli

    Full Text Available ABSTRACT Azithromycin is a water-insoluble drug, with a very low bioavailability. In order to increase the solubility and dissolution rate, and consequently increase the bioavailability of poorly-soluble drugs (such as azithromycin, various techniques can be applied. One of such techniques is "solid dispersion". This technique is frequently used to improve the dissolution rate of poorly water-soluble compounds. Owing to its low solubility and dissolution rate, azithromycin does not have a suitable bioavailability. Therefore, the main purpose of this investigation was to increase the solubility and dissolution rate of azithromycin by preparing its solid dispersion, using different Polyethylene glycols (PEG. Preparations of solid dispersions and physical mixtures of azithromycin were made using PEG 4000, 6000, 8000, 12000 and 20000 in various ratios, based on the solvent evaporation method. From the studied drug release profile, it was discovered that the dissolution rate of the physical mixture, as the well as the solid dispersions, were higher than those of the drug alone. There was no chemical incompatibility between the drug and polymer from the observed Infrared (IR spectra. Drug-polymer interactions were also investigated using Differential Scanning Calorimetry (DSC, Powder X-Ray Diffraction (PXRD and Scanning Election Microscopy (SEM. In conclusion, the dissolution rate and solubility of azithromycin were found to improve significantly, using hydrophilic carriers, especially PEG 6000.

  10. Streamlined sample cleanup using combined dispersive solid-phase extraction and in-vial filtration for analysis of pesticides and environmental pollutants in shrimp

    Science.gov (United States)

    A new method of sample preparation was developed and is reported for the first time. The approach combines in-vial filtration with dispersive solid-phase extraction (d-SPE) in a fast and convenient cleanup of QuEChERS (quick, easy, cheap, effective, rugged, and safe) extracts. The method was appli...

  11. Polypyrrole-magnetite dispersive micro-solid-phase extraction combined with ultraviolet-visible spectrophotometry for the determination of rhodamine 6G and crystal violet in textile wastewater.

    Science.gov (United States)

    Kamaruddin, Amirah Farhan; Sanagi, Mohd Marsin; Wan Ibrahim, Wan Aini; Md Shukri, Dyia S; Abdul Keyon, Aemi S

    2017-11-01

    Polypyrrole-magnetite dispersive micro-solid-phase extraction method combined with ultraviolet-visible spectrophotometry was developed for the determination of selected cationic dyes in textile wastewater. Polypyrrole-magnetite was used as adsorbent due to its thermal stability, magnetic properties, and ability to adsorb Rhodamine 6G and crystal violet. Dispersive micro-solid-phase extraction parameters were optimized, including sample pH, adsorbent amount, extraction time, and desorption solvent. The optimum polypyrrole-magnetite dispersive micro-solid phase-extraction conditions were sample pH 8, 60 mg polypyrrole-magnetite adsorbent, 5 min of extraction time, and acetonitrile as the desorption solvent. Under the optimized conditions, the polypyrrole-magnetite dispersive micro-solid-phase extraction with ultraviolet-visible method showed good linearity in the range of 0.05-7 mg/L (R 2  > 0.9980). The method also showed a good limit of detection for the dyes (0.05 mg/L) and good analyte recoveries (97.4-111.3%) with relative standard deviations extraction and determination of dyes at trace concentration levels. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Amorphous superconductors

    International Nuclear Information System (INIS)

    Missell, F.P.

    1985-01-01

    We describe briefly the strong coupling superconductivity observed in amorphous alloys based upon simple metals. For transition metal alloys we discuss the behavior of the superconducting transition temperature T c , the upper critical field H (sub)c2 and the critical current J c . A survey of current problems is presented. (author) [pt

  13. Enhancement of in-vitro drug dissolution of ketoconazole for its optimal in-vivo absorption using Nanoparticles and Solid Dispersion forms of the drug

    Science.gov (United States)

    Syed, Mohammed Irfan

    Ketoconazole is one of the most widely prescribed oral antifungal drugs for the systemic treatment of various fungal infections. However, due its hydrophobic nature and poor solubility profiles in the gastro-intestinal fluids, variations in its bioavailability have been documented. Therefore, to enhance its dissolution in the biological fluids, this study was initiated to develop and evaluate Nanoparticles and Solid Dispersion forms of the drug. Nanoparticles of ketoconazole were developed by Wet Bead Milling technique using PVP-10k as the stabilizing material at a weight ratio of (2:1). Solid dispersion powder was prepared by Hot Melt method using PEG-8000 at a weight ratio of (1:2). A commercial product containing 200mg of ketoconazole tablet and pure drug powder were used as the control for comparison purposes. The dissolution studies were carried out in SGF, SIF, USP; and SIF with 0.2% sodium lauryl sulfate using the USP-II method for a 2 hours period. Physical characterizations were carried out using SEM, DSC, XRD and FTIR studies. Wet Bead Milling method yielded nanoparticles in the particles size range of (100-300nm.). First all samples were evaluated for their in-vitro dissolution in SGF at pH=1.2. After 15 minutes, the amounts of drug dissolved were observed to be 27% from both the pure powder and commercial tablet (control), 29% from solid dispersion and 100% from the Nanoparticles dosage form. This supports the fact that Nanoparticles had a strong influence on the dissolution rate of the drug and exhibited much faster dissolution of ketoconazole. When the same formulations were studied in the SIF, USP medium, the control formulation gave 3%, solid dispersion 8% and Nanoparticles 8% drug dissolution after 2 hours period. This could be because the weakly basic ketoconazole drug remained un-dissociated in the alkaline medium. Since this medium was unable to clearly distinguish the dissolution profiles from different formulation of the drug, the SIF solution

  14. Analysis of malachite green in aquatic products by carbon nanotube-based molecularly imprinted - matrix solid phase dispersion.

    Science.gov (United States)

    Wang, Yu; Chen, Ligang

    2015-10-01

    A simple method based on matrix solid phase dispersion (MSPD) using molecularly imprinted polymers (MIPs) as sorbents for selective extraction of malachite green (MG) from aquatic products was developed. The MIPs were prepared by using carbon nanotube as support, MG as template, methacrylic acid as functional monomer, ethyleneglycol dimethacrylate as crosslinker and methylene chloride as solvent. The MIPs were characterized by Fourier transform infrared spectrometry and transmission electron microscopy. The isothermal adsorption, kinetics absorption and selective adsorption experiments were carried out. We optimized the extraction conditions as follows: the ratio of MIPs to sample was 2:3, the dispersion time was 15min, washing solvent was 4mL 50% aqueous methanol and elution solvent was 3mL methanol-acetic acid (98: 2, v/v). Once the MSPD process was completed, the MG extracted from aquatic products was determined by high performance liquid chromatography. The detection limit of MG was 0.7μgkg(-1). The relative standard deviations of intra-day and inter-day were obtained in the range of 0.9%-4.7% and 3.4%-9.8%, respectively. In order to evaluate the applicability and reliability of the proposed method, it was applied to determine MG in different aquatic products samples including fish, shrimp, squid and crabs. The satisfied recoveries were in the range of 89.2%-104.6%. The results showed that this method is faster, simpler and makes extraction and purification in the same system. Copyright © 2015 Elsevier B.V. All rights reserved.

  15. Vortex-homogenized matrix solid-phase dispersion for the extraction of short chain chlorinated paraffins from indoor dust samples.

    Science.gov (United States)

    Chen, Yu-Hsuan; Chang, Chia-Yu; Ding, Wang-Hsien

    2016-11-11

    A simple and effective method for determining short chain chlorinated paraffins (SCCPs) in indoor dust is presented. The method employed a modified vortex-homogenized matrix solid-phase dispersion (VH-MSPD) prior to its detection by gas chromatography - electron-capture negative-ion mass spectrometry (GC-ECNI-MS) operating in the selected-ion-monitoring (SIM) mode. Under the best extraction conditions, 0.1-g of dust sample was dispersed with 0.1-g of silica gel by using vortex (2min) instead of using a mortar and pestle (3min). After that step, the blend was transferred to a glass column containing 3-g acidic silica gel, 2-g basic silica gel, and 2-g of deactivated silica gel, used as clean-up co-sorbents. Then, target analytes were eluted with 5mL of n-hexane/dichloromethane (2:1, v/v) mixture. The extract was evaporated to dryness under a gentle stream of nitrogen. The residue was then re-dissolved in n-hexane (10μL), and subjected to GC-ECNI-MS analysis. The limits of quantitation (LOQs) ranged from 0.06 to 0.25μg/g for each SCCP congener. Precision was less than 7% for both intra- and inter-day analysis. Trueness was above 89%, which was calculated by mean extraction recovery. The VH-MSPD combined with GC-ECNI-MS was successfully applied to quantitatively detect SCCPs from various indoor dust samples, and the concentrations ranged from 1.2 to 31.2μg/g. Copyright © 2016 Elsevier B.V. All rights reserved.

  16. The Preparation and Performances of Self-Dispersed Nanomicron Emulsified Wax Solid Lubricant Ewax for Drilling Fluids

    Directory of Open Access Journals (Sweden)

    Feng-shan Zhou

    2014-01-01

    Full Text Available An oil-in-water nanomicron wax emulsion with oil phase content 45 wt% was prepared by using the emulsifying method of surfactant-in-oil. The optimum prepared condition is 85°C, 20 min, and 5 wt% complex emulsifiers. Then the abovementioned nanomicron emulsifying wax was immersed into a special water-soluble polymer in a certain percentage by the semidry technology. At last, a solidified self-dispersed nanomicron emulsified wax named as Ewax, a kind of solid lubricant for water based drilling fluid, was obtained after dried in the special soluble polymer containing emulsifying wax in low temperature. It is shown that the adhesion coefficient reduced rate (ΔKf is 73.5% and the extreme pressure (E-P friction coefficient reduced rate (Δf is 77.6% when the produced Ewax sample was added to fresh water based drilling fluid at dosage 1.0 wt%. In comparison with other normal similar liquid products, Ewax not only has better performances of lubrication, filtration loss control property, heat resistance, and tolerance to salt and is environmentally friendly, but also can solve the problems of freezing in the winter and poor storage stability of liquid wax emulsion in oilfield applications.

  17. Impact of noise barriers on the dispersal of solid pollutants from car emissions and their deposition in soil

    Directory of Open Access Journals (Sweden)

    Wawer Małgorzata

    2017-03-01

    Full Text Available Despite the existence of various methods aimed at protecting the environment from the negative influence of roads, there is a lack of adequate techniques for monitoring and reducing the spread of roadside pollution into the air and soils. The aim of this study was to assess the impact of noise barriers (sound walls on the dispersal and soil deposition of solid pollutants from car emissions, based on both quantitative and qualitative analysis. Magnetic susceptibility measurements, trace elements analyses, and platinum (Pt and rhodium (Rh content determinations were performed on soil samples collected in the vicinity of various types of noise barrier. Previous investigations have shown that most traffic emissions are deposited in the close vicinity of roads (up to 10 m, with pollution levels decreasing with increasing distance from the road edge. However, the results of the present study indicate that this distribution is disturbed in areas in which noise barriers are located. Moreover, additional soil enrichment with trace elements was observed at approx. 10-15 m behind the barriers. The spatial distribution of trace elements contents in the tested soil samples corresponded to the magnetic susceptibility values. High Fe, Zn, Mn and Pb levels were observed adjacent to noise barriers composed of sawdust concrete and steel panels.

  18. Matrix solid-phase dispersion extraction of organophosphorus pesticide using SiO2-poly(N-vinylimidazole)

    International Nuclear Information System (INIS)

    Gutiérrez-Solís, M C; Muñoz-Rodríguez, D; Carrera-Figueiras, C; Ávila-Ortega, A; Medina-Peralta, S

    2013-01-01

    A sorbent material based on silica particles modified with poly(N-vinylimidazole) (SiO 2 -PVI) has been evaluated for the treatment of samples by matrix solid-phase dispersion (MSPD). The extraction of four organophosphorus pesticides was done from a spiked tomato and the extracts were analyzed by gas chromatography coupled to mass spectrometry. Six elution solvents were evaluated and acetone was selected due to better recovery of the four pesticides and low background signal in the chromatograms. A factorial design 2 4 was used for selection of extraction conditions. The factors were contact time, acetone volume, treatment (with or without freeze-drying) and adsorbent (SiO 2 or SiO 2 -PVI). The best recoveries were obtained using 15 minutes of contact, 2 mL of solvent and sorbent without freeze-drying. The recoveries were between 60 and 83% for SiO 2 -PVI in spiked tomato with 0.2 and 0.8μg/g.

  19. Polar Quassinoids in Standardized Eurycoma longifolia Extract Formulated into a Lipid-Based Solid Dispersion to Improve Rat Sperm Count.

    Science.gov (United States)

    Ma, Hai-Qiu; Ebrahimi, Forough; Low, Bin-Seng; Khan, Nurzalina Abdul Karim; Chan, Kit-Lam

    2017-12-01

    Eurycoma longifolia Jack is popularly sought in Southeast Asian countries for traditional remedies to improve sexual performance and fertility. 13α(21)-Epoxyeurycomanone and eurycomanone, two major quassinoids in a root extract (TAF2) were reported to improve rat spermatogenesis and fertility. Unfortunately, these quassinoids possess low bioavailability because of high aqueous solubility and low lipid membrane permeability. Often, other possible barriers may be P-glycoprotein (P-gp) efflux in the gut and presystemic hepatic metabolism. The present study attempted to solve these problems by formulating a lipid-based solid dispersion (TAF2-SD) of optimized mixture of TAF2 and emulsifiers, which was then orally administered to rats prior to sperm count analysis. The TAF2-SD-treated rats showed significantly twofold (p < 0.001) and fourfold (p < 0.001) higher sperm count than did TAF2-treated and vehicle-treated (control) rats, respectively. The study also demonstrated no significant in vitro ileal absorption changes of the quassinoids by P-gp efflux inhibitors and concentration change or secondary metabolite formation upon in vitro incubation with rat liver homogenates, suggesting that P-gp-mediated efflux and presystemic metabolism were not limiting their bioavailability. Further study on orally TAF2-treated rats confirmed that the area under the curve and bioavailability curve of each quassinoid in the absence and presence of ketoconazole were unchanged. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Pediatric suppositories of sulpiride solid dispersion for treatment of Tourette syndrome: in vitro and in vivo investigations.

    Science.gov (United States)

    Zidan, Ahmed S; Emam, Sherif E; Shehata, Tamer M; Ghazy, Fakhr-eldin S

    2015-06-01

    Pharmaceutical development was adopted in the current study to propose a pediatric rectal formulation of sulpiride as a substitute to the available oral or parenteral formulations in the management of Tourette syndrome (TS). The goal was to formulate a product that is easy to use, stable, and highly bioavailable and to achieve a rapid clinical efficacy. Towards this aim, sulpiride solid dispersion (SD) with tartaric acid at a weight ratio of 1:0.25 was incorporated into different suppository bases, namely witepsol W25, witepsol H15, witepsol E75, suppocire NA, suppocire A, glycerogelatin, and polyethylene glycols. The formulae were evaluated in vitro using different pharmacotechnical methods such as visual, melting, weight and content uniformities, drug release, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD) analyses. In vivo bioavailability was also assessed in rabbits to compare the bioavailability of either raw sulpiride-incorporated or its SD-incorporated witepsol H15-based suppositories to its oral suspension (reference). Sulpiride SD-incorporated witepsol H15 formulation showed acceptable in vitro characteristics with a bioavailability of 117% relative to oral dosing, which excel that in humans (27% after dosing of oral product). In addition, the proposed formula not only passed the 6-month stability study but also proposed a promising scale-up approach. Hence, it showed a great potential for pediatric product development to manage TS in rural areas.

  1. Sulfonated nanocellulose for the efficient dispersive micro solid-phase extraction and determination of silver nanoparticles in food products.

    Science.gov (United States)

    Ruiz-Palomero, Celia; Soriano, M Laura; Valcárcel, Miguel

    2016-01-08

    This paper reports a simple approach to Analytical Nanoscience and Nanotechnology (AN&N) that integrates the nanotool, sulfonated nanocellulose (s-NC), and nanoanalyte, silver nanoparticles (AgNPs), in the same analytical process by using an efficient, environmentally friendly dispersive micro solid-phase extraction (D-μSPE) capillary electrophoresis (CE) method with s-NC as sorbent material. Introducing negatively charged sulfate groups onto the surface of cellulose enhances its surface chemistry and enables the extraction and preconcentration of AgNPs of variable diameter (10, 20 and 60nm) and shell composition (citrate and polyvinylpyrrolidone coatings) from complex matrices into a cationic surfactant. In this way, AgNPs of diverse nature were successfully extracted onto the s-NC sorbent and then desorbed into an aqueous solution containing thiotic acid (TA) prior to CE without the need for any labor-intensive cleanup. The ensuing eco-friendly D-μSPE method exhibited a linear response to AgNPs with a limit of detection (LOD) of 20μg/L. Its ability to specifically recognize AgNPs of different sizes was checked in orange juice and mussels, which afforded recoveries of 70.9-108.4%. The repeatability of the method at the limit of quantitation (LOQ) level was 5.6%. Based on the results, sulfonated nanocellulose provides an efficient, cost-effective analytical nanotool for the extraction of AgNPs from food products. Copyright © 2015 Elsevier B.V. All rights reserved.

  2. Determination of five pyrethroids in tea drinks by dispersive solid phase extraction with polyaniline-coated magnetic particles.

    Science.gov (United States)

    Wang, Yuanpeng; Sun, Ying; Gao, Yan; Xu, Bo; Wu, Qiong; Zhang, Hanqi; Song, Daqian

    2014-02-01

    The polyaniline-coated magnetic particles with bowl-shaped morphology (Fe3O4/C/PANI microbowls) were successfully prepared and characterized by scanning electron microscopy, transmission electron microscopy and vibrating sample magnetometry. The prepared microbowls were used as the magnetic adsorbent in dispersive solid phase extraction of five pyrethroids, including cyhalothrin, beta-cypermethrin, esfenvalerate, permethrin and bifenthrin in plain tea drinks. The effects of experiment factors, including amount of Fe3O4/C/PANI microbowls, pH value, ultrasound extraction time and desorption conditions, were investigated. The extraction recoveries obtained with 8 mg of magnetic microbowls were satisfactory, and the microbowls can be reused after easy washing. Thus, a simple, selective and effective method for the determination of the pyrethroids was established successfully. The results showed that the method had good linearity (r=0.9992-0.9998), and the limits of detections (LODs) were from 0.025 to 0.032 ng mL(-1). The intra-day and inter-day relative standard deviations (RSDs) were in the range of 2.4-6.1% and 3.5-8.8%, respectively. Recoveries obtained by analyzing the real tea drinks were in the range of 72.1-118.4%. © 2013 Published by Elsevier B.V.

  3. Determination of soy proteins in food samples by dispersive solid-phase immunoextraction and dynamic long-wavelength fluorometry

    International Nuclear Information System (INIS)

    Molina-Delgado, María Ángeles; Aguilar-Caballos, María Paz; Gomez-Hens, Agustina

    2013-01-01

    We report on a method for the determination of soy proteins in food samples via dispersive solid-phase immunoextraction using gold-coated magnetic nanoparticles (NPs) as a support. Soy proteins were first extracted using anti-soy protein antibodies immobilized on the NPs, and then quantified by measuring the increase in fluorescence of the long-wavelength fluorophore cresyl violet in the presence of the anionic surfactant sodium dodecyl sulfate at neutral pH in a flow system. The method involves the use of two standard or sample aliquots. The fluorescence intensity of one aliquot is directly measured whereas that of the other aliquot is measured after immunoextraction. The difference between the peak heights of both aliquots serves as the analytical information that is directly proportional to the protein concentration. The limit of detection is 0.35 mg L −1 , the linear range is from 1 to 15 mg L −1 , and the relative standard deviation is < 5 %. Proteins such as bovine serum albumin and globulins do not interfere at the same concentration level. The method was applied to the analysis of soy-based beverages and gave recoveries in the range between 80.0 and 107.3 %. (author)

  4. Micro-matrix solid-phase dispersion coupled with MEEKC for quantitative analysis of lignans in Schisandrae Chinensis Fructus using molecular sieve TS-1 as a sorbent.

    Science.gov (United States)

    Chu, Chu; Wei, Mengmeng; Wang, Shan; Zheng, Liqiong; He, Zheng; Cao, Jun; Yan, Jizhong

    2017-09-15

    A simple and effective method was developed for determining lignans in Schisandrae Chinensis Fructus by using a micro-matrix solid phase dispersion (MSPD) technique coupled with microemulsion electrokinetic chromatography (MEEKC). Molecular sieve, TS-1, was applied as a solid supporting material in micro MSPD extraction for the first time. Parameters that affect extraction efficiency, such as type of dispersant, mass ratio of the sample to the dispersant, grinding time, elution solvent and volume were optimized. The optimal extraction conditions involve dispersing 25mg of powdered Schisandrae samples with 50mg of TS-1 by a mortar and pestle. A grinding time of 150s was adopted. The blend was then transferred to a solid-phase extraction cartridge and the target analytes were eluted with 500μL of methanol. Moreover, several parameters affecting MEEKC separation were studied, including the type of oil, SDS concentration, type and concentration of cosurfactant, and concentration of organic modifier. A satisfactory linearity (R>0.9998) was obtained, and the calculated limits of quantitation were less than 2.77μg/mL. Finally, the micro MSPD-MEEKC method was successfully applied to the analysis of lignans in complex Schisandrae fructus samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Trace determination of five triazole fungicide residues in traditional Chinese medicine samples by dispersive solid-phase extraction combined with ultrasound-assisted dispersive liquid-liquid microextraction and UHPLC-MS/MS.

    Science.gov (United States)

    Ma, Shuping; Yuan, Xucan; Zhao, Pengfei; Sun, Hong; Ye, Xiu; Liang, Ning; Zhao, Longshan

    2017-08-01

    A novel and reliable method for determination of five triazole fungicide residues (triadimenol, tebuconazole, diniconazole, flutriafol, and hexaconazol) in traditional Chinese medicine samples was developed using dispersive solid-phase extraction combined with ultrasound-assisted dispersive liquid-liquid microextraction before ultra-high performance liquid chromatography with tandem mass spectrometry. The clean up of the extract was conducted using dispersive solid-phase extraction by directly adding sorbents into the extraction solution, followed by shaking and centrifugation. After that, a mixture of 400 μL trichloromethane (extraction solvent) and 0.5 mL of the above supernatant was injected rapidly into water for the dispersive liquid-liquid microextraction procedure. The factors affecting the extraction efficiency were optimized. Under the optimum conditions, the calibration curves showed good linearity in the range of 2.0-400 (tebuconazole, diniconazole, and hexaconazole) and 4.0-800 ng/g (triadimenol and flutriafol) with the regression coefficients higher than 0.9958. The limit of detection and limit of quantification for the present method were 0.5-1.1 and 1.8-4.0 ng/g, respectively. The recoveries of the target analytes ranged from 80.2 to 103.2%. The proposed method has been successfully applied to the analysis of five triazole fungicides in traditional Chinese medicine samples, and satisfactory results were obtained. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. Synthesis and application of mesoporous molecular sieve for miniaturized matrix solid-phase dispersion extraction of bioactive flavonoids from toothpaste, plant, and saliva.

    Science.gov (United States)

    Cao, Wan; Cao, Jun; Ye, Li-Hong; Xu, Jing-Jing; Hu, Shuai-Shuai; Peng, Li-Qing

    2015-12-01

    This article describes the use of the mesoporous molecular sieve KIT-6 as a sorbent in miniaturized matrix solid-phase dispersion (MSPD) in combination with ultra-performance LC for the determination of bioactive flavonoids in toothpaste, Scutellariae Radix, and saliva. In this study, for the first time, KIT-6 was used as a sorbent material for this mode of extraction. Compared with common silica-based sorbents (C18 and activated silica gel), the proposed KIT-6 dispersant with a three-dimensional cubic Ia3d structure and highly ordered arrays of mesoporous channels exhibits excellent adsorption capability of the tested compounds. In addition, several experimental variables, such as the mass ratio of sample to dispersant, grinding time, and elution solvent, were optimized to maximize the extraction efficiency. The proposed analytical method is simple, fast, and entails low consumption of samples, dispersants and elution solvents, thereby meeting "green chemistry" requirements. Under the optimized conditions, the recoveries of three bioactive flavonoids obtained by analyzing the spiked samples were from 89.22 to 101.17%. Also, the LODs and LOQs for determining the analytes were in the range of 0.02-0.04 μg/mL and 0.07-0.13 μg/mL, respectively. Finally, the miniaturized matrix solid-phase dispersion method was successfully applied to the analysis of target solutes in real samples, and satisfactory results were obtained. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Synthesis and characterisation of composite based biohydroxyapatite bovine bone mandible waste (BHAp) doped with 10 wt % amorphous SiO{sub 2} from rice husk by solid state reaction

    Energy Technology Data Exchange (ETDEWEB)

    Asmi, Dwi, E-mail: dwiasmi82@yahoo.com, E-mail: dwi.asmi@fmipa.unila.ac.id; Sulaiman, Ahmad, E-mail: ahmadsulaiman@yahoo.co.id; Oktavia, Irene Lucky, E-mail: ireneluckyo@gmail.com [Department of Physics, Faculty of Mathematics and Natural Sciences, University of Lampung Jl. Sumantri Brojonegoro No.1 Gedung Meneng Bandar Lampung 35145 (Indonesia); Badaruddin, Muhammad, E-mail: mbruddin@eng.unila.ac.id [Department of Mechanical Engineering, Faculty of Engineering, University of Lampung Jl. Sumantri Brojonegoro No.1 Gedung Meneng Bandar Lampung 35145 (Indonesia); Zulfia, Anne, E-mail: anne@metal.ui.ac.id [Department of Metallurgy and Materials Engineering, Faculty of Engineering, University of Indonesia, Kampus Baru-UI, Depok 16424 (Indonesia)

    2016-04-19

    Effect of 10 wt% amorphous SiO{sub 2} from rice husk addition on the microstructures of biohydroxyapatite (BHAp) obtained from bovine bone was synthesized by solid state reaction. In this study, biohydroxyapatite powder was obtained from bovine bone mandible waste heat treated at 800 °C for 5 h and amorphous SiO{sub 2} powder was extracted from citric acid leaching of rice husk followed by combustion at 700°C for 5 h. The composite powder then mixed and sintered at 1200 °C for 3 h. X-ray diffraction (XRD), Fourier transformed infrared (FTIR) spectroscopy and Scanning electron microscopy (SEM) techniques are utilized to characterize the phase relations, functional group present and morphology of the sample. The study has revealed that the processing procedures played an important role in microstructural development of BHAp-10 wt% SiO{sub 2} composite. The XRD study of the raw material revealed that the primary phase material in the heat treated of bovine bone mandible waste is hydroxyapatite and in the combustion of rice husk is amorphous SiO{sub 2}. However, in the composite the hydroxyapatite, β-tricalcium phosphate, and calcium phosphate silicate were observed. The FTIR result show that the hydroxyl stretching band in the composite decrease compared with those of hydroxyapatite spectra and the evolution of morphology was occurred in the composite.

  8. Solvent-assisted dispersive solid-phase extraction: A sample preparation method for trace detection of diazinon in urine and environmental water samples.

    Science.gov (United States)

    Aladaghlo, Zolfaghar; Fakhari, Alireza; Behbahani, Mohammad

    2016-09-02

    In this research, a sample preparation method termed solvent-assisted dispersive solid-phase extraction (SA-DSPE) was applied. The used sample preparation method was based on the dispersion of the sorbent into the aqueous sample to maximize the interaction surface. In this approach, the dispersion of the sorbent at a very low milligram level was received by inserting a solution of the sorbent and disperser solvent into the aqueous sample. The cloudy solution created from the dispersion of the sorbent in the bulk aqueous sample. After pre-concentration of the diazinon, the cloudy solution was centrifuged and diazinon in the sediment phase dissolved in ethanol and determined by gas chromatography-flame ionization detector. Under the optimized conditions (pH of solution=7.0, Sorbent: benzophenone, 2%, Disperser solvent: ethanol, 500μL, Centrifuge: centrifuged at 4000rpm for 3min), the method detection limit for diazinon was 0.2, 0.3, 0.3 and 0.3μgL(-1) for distilled water, lake water, waste water and urine sample, respectively. Furthermore, the pre-concentration factor was 363.8, 356.1, 360.7 and 353.38 in distilled water, waste water, lake water and urine sample, respectively. SA-DSPE was successfully used for trace monitoring of diazinon in urine, lake and waste water samples. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Crystalline Ethylene Oxide and Propylene Oxide Triblock Copolymer Solid Dispersion Enhance Solubility, Stability and Promoting Time- Controllable Release of Curcumin.

    Science.gov (United States)

    Alves, Thais F R; das Neves Lopes, Franciely C C; Rebelo, Marcia A; Souza, Juliana F; da Silva Pontes, Katiusca; Santos, Carolina; Severino, Patricia; Junior, Jose M O; Komatsu, Daniel; Chaud, Marco V

    2018-01-01

    The design and development of an effective medicine are, however, often faced with a number of challenges. One of them is the close relationship of drug's bioavailability with solubility, dissolution rate and permeability. The use of curcumin's (CUR) therapeutic potential is limited by its poor water solubility and low chemical stability. The purpose was to evaluate the effect of polymer and solid dispersion (SD) preparation techniques to enhance the aqueous solubility, dissolution rate and stability of the CUR. The recent patents on curcumin SD were reported as (i) curcumin with polyvinylpyrrolidone (CN20071 32500 20071214, WO2006022012 and CN20151414227 20150715), (ii) curcumin-zinc/polyvinylpyrrolidone (CN20151414227 20150715), (iii) curcumin-poloxamer 188 (CN2008171177 20080605), (iv) curcumin SD prepared by melting method (CN20161626746-20160801). SD obtained by co-preciptation or microwave fusion and the physical mixture of CUR with Poloxamer-407 (P-407), Hydroxypropylmetylcellulose-K4M (HPMC K4M) and Polyvinylpyrrolidone-K30 (PVP-K30) were prepared at the ratios of 1:2; 1:1 and 2:1. The samples were evaluated by solubility, stability, dissolution rate and characterized by SEM, PXRD, DSC and FTIR. The solubility, stability (pH 7.0) and dissolution rate were significantly greater for SD (CUR:P-407 1:2). The PXRD,SEM and DSC indicated a change in the crystalline state of CUR. The enhancement of solubility was dependent on a combination of factors including the weight ratio, preparation techniques and carrier properties. The drug release data fitted well with the Weibull equation, indicating that the drug release was controlled by diffusion, polymer relaxation and erosion occurring simultaneously. Thus, these SDs, specifically CUR:P-407 1:2 w/w, can overcome the barriers of poor bioavailability to reap many beneficial properties. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Simultaneous in situ derivatization and ultrasound-assisted dispersive magnetic solid phase extraction for thiamine determination by spectrofluorimetry.

    Science.gov (United States)

    Tarigh, Ghazale Daneshvar; Shemirani, Farzaneh

    2014-06-01

    A simple and rapid method for the simultaneous in situ derivatizaion, preconcentration and extraction of thiamine (vitamin B1) as a model analyte was developed by a novel quantitative method, namely ultrasound-assisted dispersive magnetic solid phase extraction spectrofluorimetry (USA-DMSPE-FL) from different real samples. This method consists of sample preparation, in situ derivatization, exhaustive extraction and clean up by a single process. High extraction efficiency and in situ derivatization in a short period of time is the main advantages of this procedure. For this purpose, the reusable magnetic multi-wall carbon nanotube (MMWCNT) nanocomposite was used as an adsorbent for preconcentration and determination of thiamine. Thiamine was, simultaneously, in situ derivatized as thiochrome by potassium hexacyanoferrate (III) and adsorbed on MMWCNT in an ultrasonic water bath. The MMWCNTs were then collected using an external magnetic field. Subsequently, the extracted thiochrome was washed from the surface of the adsorbent and determined by spectrofluorimetry. The developed method, which has been analytically characterized under its optimal operating conditions, allows the detection of the analyte in the samples with method detection limits of 0.37 µg L(-1). The repeatability of the method, expressed as the relative standard deviation (RSD, n=6), varies between 2.0% and 4.8% in different real samples, while the enhancement factor is 197. The proposed procedure has been applied for the determination of thiamine in biological (serum and urine), pharmaceutical (multivitamin tablet and B complex syrup) and foodstuff samples (cereal, wheat flour, banana and honey) with the good recoveries in the range from 90% to 105%. Copyright © 2014 Elsevier B.V. All rights reserved.

  11. Investigation of physicochemical factors affecting the stability of a pH-modulated solid dispersion and a tablet during storage.

    Science.gov (United States)

    Tran, Phuong Ha-Lien; Tran, Thao Truong-Dinh; Park, Jun-Bom; Min, Dong Hun; Choi, Han-Gon; Han, Hyo-Kyung; Rhee, Yun-Seok; Lee, Beom-Jin

    2011-07-29

    The stability of solid dispersions (SD) during storage is of concern. We prepared the pH-modulated SD (pSD) and compressed tablets consisting of polyethylene glycol (PEG) 6000 as a carrier, drug and MgO (alkalizer). Telmisartan (TEL), an ionizable poorly water-soluble drug, was chosen as a model drug. The changes in physicochemical factors such as the dissolution rate, drug crystallinity, microenvironmental pH (pH(M)) and intermolecular interactions of the pSD and the tablets were investigated over 3 months under different temperature and relative humidity (RH) conditions: refrigerator (5-8 °C), 25 °C/32% RH, 25 °C/55% RH, 25 °C/75% RH, 40°C/32% RH, 40 °C/55% RH, and 40 °C/75% RH. Differential scanning calorimetry (DSC) analysis of all samples revealed no distinct changes in the drug melting point. In contrast, powder X-ray diffraction (PXRD) diffractograms revealed that samples stored at 40 °C/75% RH for 1 month, 25 °C/75% RH for 3 months and 40 °C at all humidity conditions for 3 months showed gradual recrystallization of the drug. Fourier transform infrared (FTIR) spectra indicated a reduced intensity of intermolecular interactions between TEL and MgO in the pSD and tablet. The pH(M) also gradually decreased. These altered physicochemical factors under the stressed conditions resulted in decreased dissolution profiles in intestinal fluid (pH 6.8). In contrast, the dissolution rate in gastric fluid (pH 1.2) was almost unchanged because of the high intrinsic solubility of TEL at this pH. Copyright © 2011 Elsevier B.V. All rights reserved.

  12. Solid dispersion of dutasteride using the solvent evaporation method: Approaches to improve dissolution rate and oral bioavailability in rats.

    Science.gov (United States)

    Choi, Jin-Seok; Lee, Sang-Eun; Jang, Woo Suk; Byeon, Jong Chan; Park, Jeong-Sook

    2018-09-01

    The aim of this study was to develop a dutasteride (DUT) solid dispersion (SD) using hydrophilic substances to enhance its dissolution (%) and oral bioavailability in rats. DUT-SD formulations were prepared with various co-polymers using a solvent evaporation method. The physical properties of DUT-SD formulations were confirmed using field emission scanning electron microscopy (FE-SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and attenuated total reflectance Fourier transform infrared (ATR-FT-IR) spectroscopy. The toxicity and oral bioavailability of DUT-SD formulations were evaluated. Tocopheryl polyethylene glycol-1000-succinate (TPGS) was chosen as the solubilizer; and methylene chloride, and Aerosil® 200 or microcrystalline cellulose (MCC) were chosen as the solvent and carrier, respectively, based on a solubility test and pre-dissolution study. The dissolution levels of DUT-SD formulations were 86.3 ± 2.3% (F15) and 95.1 ± 1.9% (F16) after 1 h, which were higher than those of the commercial product, i.e., Avodart® (75.8 ± 1.5%) in 0.1 N HCl containing 1% (w/v) sodium lauryl sulfate (SLS). The F16 formulation was found to be stable, after assessing its dissolution (%) and drug content (%) for 6 months. The DUT-SD formulations resulted in relative bioavailability (BA) values of 126.4% (F15) and 132.1% (F16), which were enhanced compared to that of Avodart®. Dissolution (%) and relative BA values were both increased by hydrogen interaction between TPGS and DUT. This study might contribute to a new formulation (powder) whose oral bioavailability is greater than that of Avodart® (soft capsule), which could facilitate to the use of the SD system during the production process. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Electrical and Magnetic Properties of Binary Amorphous Transition Metal Alloys.

    Science.gov (United States)

    Liou, Sy-Hwang

    The electrical, superconductive and magnetic properties of several binary transition metal amorphous and metastable crystalline alloys, Fe(,x)Ti(,100-x) (30 (LESSTHEQ) x (LESSTHEQ) 100), Fe(,x)Zr(,100-x) (20 (LESSTHEQ) x (LESSTHEQ) 93), Fe(,x)Hf(,100-x) (20 (LESSTHEQ) x (LESSTHEQ) 100), Fe(,x)Nb(,100 -x) (22 (LESSTHEQ) x (LESSTHEQ) 85), Ni(,x)Nb(,100-x) (20 (LESSTHEQ) x (LESSTHEQ) 80), Cu(,x)Nb(,100-x) (10 (LESSTHEQ) x (LESSTHEQ) 90) were studied over a wide composition range. Films were made using a magnetron sputtering system, and the structure of the films was investigated by energy dispersive x-ray diffraction. The composition region of each amorphous alloys system was determined and found in good agreement with a model proposed by Egami and Waseda. The magnetic properties and hyperfine interactions in the films were investigated using a conventional Mossbauer spectrometer and a ('57)Co in Rh matrix source. In all Fe-early transition metal binary alloys systems, Fe does not retain its moment in the low iron concentration region and the result is that the critical concentration for magnetic order (x(,c)) is much larger than anticipated from percolation considerations. A direct comparison between crystalline alloys and their amorphous counterparts of the same composition illustrate no clear correlation between crystalline and amorphous states. Pronounced discontinuities in the magnetic properties with variation in Fe content of all Fe-early transition metal alloys at phase boundaries separating amorphous and crystalline states have been observed. This is caused by the differences in the atomic arrangement and the electronic structure between crystalline and amorphous solids. The temperature dependence of resistivity, (rho)(T), of several binary amorphous alloys of Fe-TM (where TM = Ti, Zr, Hf, Nb etc.) has been studied from 2K to 300K. The Fe-poor (x x(,c)) samples have distinctive differences in (rho)(T) at low temperature (below 30K). All the magnetic samples

  14. A novel osmotic pump-based controlled delivery system consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen: in vitro and in vivo evaluation.

    Science.gov (United States)

    Li, Shujuan; Wang, Xiaoyu; Wang, Yingying; Zhao, Qianqian; Zhang, Lina; Yang, Xinggang; Liu, Dandan; Pan, Weisan

    2015-01-01

    In this study, a novel controlled release osmotic pump capsule consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen (FP) was developed to improve the solubility and oral bioavailability of FP and to minimize the fluctuation of plasma concentration. The pH-modulated solid dispersion containing FP, Kollidon® 12 PF and Na2CO3 at a weight ratio of 1/4.5/0.02 was prepared using the solvent evaporation method. The osmotic pump capsule was assembled by semi-permeable capsule shell of cellulose acetate (CA) prepared by the perfusion method. Then, the solid dispersion, penetration enhancer, and suspending agents were tableted and filled into the capsule. Central composite design-response surface methodology was used to evaluate the influence of factors on the responses. A second-order polynomial model and a multiple linear model were fitted to correlation coefficient of drug release profile and ultimate cumulative release in 12 h, respectively. The actual response values were in good accordance with the predicted ones. The optimized formulation showed a complete drug delivery and zero-order release rate. Beagle dogs were used to be conducted in the pharmacokinetic study. The in vivo study indicated that the relative bioavailability of the novel osmotic pump system was 133.99% compared with the commercial preparation. The novel controlled delivery system with combination of pH-modulated solid dispersion and osmotic pump system is not only a promising strategy to improve the solubility and oral bioavailability of poorly soluble ionizable drugs but also an effective way to reduce dosing frequency and minimize the plasma fluctuation.

  15. Determination of haloacetic acids in water using layered double hydroxides as a sorbent in dispersive solid-phase extraction followed by liquid chromatography with tandem mass spectrometry.

    Science.gov (United States)

    Alsharaa, Abdulnaser; Sajid, Muhammad; Basheer, Chanbasha; Alhooshani, Khalid; Lee, Hian Kee

    2016-09-01

    In the present study, highly efficient and simple dispersive solid-phase extraction procedure for the determination of haloacetic acids in water samples has been established. Three different types of layered double hydroxides were synthesized and used as a sorbent in dispersive solid-phase extraction. Due to the interesting behavior of layered double hydroxides in an acidic medium (pH˂4), the analyte elution step was not needed; the layered double hydroxides are simply dissolved in acid immediately after extraction to release the analytes which are then directly introduced into a liquid chromatography with tandem mass spectrometry system for analysis. Several dispersive solid-phase extraction parameters were optimized to increase the extraction efficiency of haloacetic acids such as temperature, extraction time and pH. Under optimum conditions, good linearity was achieved over the concentration range of 0.05-100 μg/L with detection limits in the range of 0.006-0.05 μg/L. The relative standard deviations were 0.33-3.64% (n = 6). The proposed method was applied to different water samples collected from a drinking water plant to determine the concentrations of haloacetic acids. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Radiation amorphization of materials

    International Nuclear Information System (INIS)

    Neklyudov, I.M.; Chernyaeva, T.P.

    1993-01-01

    The results of experimental and theoretical research on radiation amorphization are presented in this analytical review. Mechanism and driving forces of radiation amorphization are described, kinetic and thermodynamic conditions of amorphization are formulated. Compositional criteria of radiation amorphization are presented, that allow to predict irradiation behaviour of materials, their tendency to radiation amorphization. Mechanism of transition from crystalline state to amorphous state are considered depending on dose, temperature, structure of primary radiation damage and flux level. (author). 134 refs., 4 tab., 25 fig

  17. Analysis of a nanocrystalline polymer dispersion of ebselen using solid-state NMR, Raman microscopy, and powder X-ray diffraction.

    Science.gov (United States)

    Vogt, Frederick G; Williams, Glenn R

    2012-07-01

    Nanocrystalline drug-polymer dispersions are of significant interest in pharmaceutical delivery. The purpose of this work is to demonstrate the applicability of methods based on two-dimensional (2D) and multinuclear solid-state NMR (SSNMR) to a novel nanocrystalline pharmaceutical dispersion of ebselen with polyvinylpyrrolidone-vinyl acetate (PVP-VA), after initial characterization with other techniques. A nanocrystalline dispersion of ebselen with PVP-VA was prepared and characterized by powder X-ray diffraction (PXRD), confocal Raman microscopy and mapping, and differential scanning calorimetry (DSC), and then subjected to detailed 1D and 2D SSNMR analysis involving ¹H, ¹³C, and ⁷⁷Se isotopes and ¹H spin diffusion. PXRD was used to show that dispersion contains nanocrystalline ebselen in the 35-60 nm size range. Confocal Raman microscopy and spectral mapping were able to detect regions where short-range interactions may occur between ebselen and PVP-VA. Spin diffusion effects were analyzed using 2D SSNMR experiments and are able to directly detect interactions between ebselen and the surrounding PVP-VA. The methods used here, particularly the 2D SSNMR methods based on spin diffusion, provided detailed structural information about a nanocrystalline polymer dispersion of ebselen, and should be useful in other studies of these types of materials.

  18. Bonding tungsten, W–Cu-alloy and copper with amorphous Fe–W alloy transition

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Song, E-mail: wangsongrain@163.com [Laboratory of Special Ceramics and Powder Metallurgy, University of Science and Technology Beijing, Beijing 100083 (China); Laboratory of Advanced Materials, Tsinghua University, Beijing 100084 (China); Ling, Yunhan, E-mail: yhling@mail.tsinghua.edu.cn [Laboratory of Advanced Materials, Tsinghua University, Beijing 100084 (China); Zhao, Pei [Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100039 (China); Zang, Nanzhi [Laboratory of Advanced Materials, Tsinghua University, Beijing 100084 (China); Wang, Jianjun [Laboratory of Special Ceramics and Powder Metallurgy, University of Science and Technology Beijing, Beijing 100083 (China); Guo, Shibin [Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190 (China); Graduate School of the Chinese Academy of Sciences, Beijing 100039 (China); Zhang, Jun [Laboratory of Advanced Materials, Tsinghua University, Beijing 100084 (China); Xu, Guiying [Laboratory of Special Ceramics and Powder Metallurgy, University of Science and Technology Beijing, Beijing 100083 (China)

    2013-05-15

    W/Cu graded materials are the leading candidate materials used as the plasma facing components in a fusion reactor. However, tungsten and copper can hardly be jointed together due to their great differences in physical properties such as coefficient of thermal expansion and melting point, and the lack of solid solubility between them. To overcome those difficulties, a new amorphous Fe–W alloy transitional coating and vacuum hot pressing (VHP) method were proposed and introduced in this paper. The morphology, composition and structure of the amorphous Fe–W alloy coating and the sintering interface of the specimens were analyzed by scanning electron microscopy (SEM), energy dispersive spectrometer (EDS) and X-ray diffraction (XRD). The thermal shock resistance of the bonded composite was also tested. The results demonstrated that amorphous structure underwent change from amorphous to nano grains during joining process, and the joined W/Cu composite can endued plasma thermal shock resistance with energy density more than 5.33 MW/m{sup 2}. It provides a new feasible technical to join refractory tungsten to immiscible copper with amorphous Fe–W alloy coating.

  19. Peculiarities of Vibration Characteristics of Amorphous Ices

    Science.gov (United States)

    Gets, Kirill V.; Subbotin, Oleg S.; Belosludov, Vladimir R.

    2012-03-01

    Dynamic properties of low (LDA), high (HDA) and very high (VHDA) density amorphous ices were investigated within the approach based on Lattice Dynamics simulations. In this approach, we assume that the short-range molecular order mainly determines the dynamic and thermodynamic properties of amorphous ices. Simulation cell of 512 water molecules with periodical boundary conditions and disordering allows us to study dynamical properties and dispersion curves in the Brillouin zone of pseudo-crystal. Existence of collective phenomena in amorphous ices which is usual for crystals but anomalous for disordered phase was confirmed in our simulations. Molecule amplitudes of delocalized (collective) as well as localized vibrations have been considered.

  20. Graphene-coated polystyrene-divinylbenzene dispersive solid-phase extraction coupled with supercritical fluid chromatography for the rapid determination of 10 allergenic disperse dyes in industrial wastewater samples.

    Science.gov (United States)

    Lou, Chaoyan; Wu, Can; Zhang, Kai; Guo, Dandan; Jiang, Lei; Lu, Yang; Zhu, Yan

    2018-05-18

    Allergenic disperse dyes are a group of environmental contaminants, which are toxic and mutagenic to human beings. In this work, a method of dispersive solid-phase extraction (d-SPE) using graphene-coated polystyrene-divinylbenzene (G@PS-DVB) microspheres coupled with supercritical fluid chromatography (SFC) was proposed for the rapid determination of 10 allergenic disperse dyes in industrial wastewater samples. G@PS-DVB microspheres were synthesized by coating graphene (G) sheets onto polystyrene-divinylbenzene (PS-DVB) polymers. Such novel sorbents were employed in d-SPE for the purification and concentration of allergenic disperse dyes in wastewater samples prior to the determination by SFC with UV detection. To achieve the maximum extraction efficiency for the target dyes, several parameters influencing d-SPE process such as sorbent dosage, extraction time, desorption conditions were investigated. SFC conditions including stationary phase, modifier composition and percentage, column temperature, backpressure and flow rate were optimized to well separate the allergenic disperse dyes. Under the optimum conditions, satisfactory linear relationship (R ≥ 0.9989) was observed with the concentration of dyes ranging from 0.02 to 10.0 μg/mL. The limits of detection (LOD, S/N = 3) for the ten dyes were in the range of 1.1-15.6 ng/mL. Recoveries for the spiked samples were between 89.1% and 99.7% with relative standard deviations (RSD) lower than 10.5% in all cases. The proposed method is time-saving, green, precise and repeatable for the analysis of the target dyes. Furthermore, the application of G@PS-DVB based d-SPE process can be potentially expanded to isolate and concentrate other aromatic compounds in various matrices and supercritical fluid chromatography methodology featuring rapidity, accuracy and green will be an ideal candidate for the analysis of these compounds. Copyright © 2018 Elsevier B.V. All rights reserved.

  1. Core-shell Fe3O4 polydopamine nanoparticles as sorbent for magnetic dispersive solid-phase extraction of copper from food samples.

    Science.gov (United States)

    Yavuz, Emre; Tokalıoğlu, Şerife; Patat, Şaban

    2018-10-15

    In the present study, core-shell Fe 3 O 4 polydopamine nanoparticles were synthesized and used for the first time as an adsorbent for the vortex assisted magnetic dispersive solid phase extraction of copper from food samples. After elution, copper in the solutions was determined by FAAS. The adsorbent was characterized using X-ray diffraction, scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller surface area, and zeta potential measurements. Various parameters affecting the magnetic dispersive solid-phase extraction were evaluated. The optimum pH and magnetic adsorbent amount were found to be 5 and 40 mg, respectively. Elution was made by 3 mL of 2 mol L -1 HNO 3 .The major advantage of the method is the fast equilibration during adsorption without the need for vortexing or shaking. The preconcentration factor and detection limit of the method were found to be 150 and 0.22 mg L -1 , respectively. The precision (as RSD%) and adsorption capacity of the method were 3.7% and 28 mg g -1 , respectively. The method was successfully verified by analyzing four certified reference materials (SPS-WW1 Batch 114 Wastewater, TMDA-53.3 Lake water, BCR-482 Lichen and 1573a Tomato Leaves) and by addition/recovery tests of copper standard solution in organic baby food, muesli, macaroni, honey, and milk samples. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Determination of six pesticides in the medicinal herb Cordia salicifolia by matrix solid-phase dispersion and gas chromatography/mass spectrometry.

    Science.gov (United States)

    de Carvalho, Pedro Henrique Viana; Prata, Vanessa de Menezes; Alves, Péricles Barreto; Navickiene, Sandro

    2009-01-01

    A simple and effective extraction method based on matrix solid-phase dispersion was developed for acephate, chlorpropham, pyrimicarb, bifenthrin, tetradifon, and phosalone in leaves of the medicinal plant Cordia salicifolia, whose extracts are commercialized in Brazil as diuretic, appetite suppressant, and weight loss products. The determination method was GC/MS with selected-ion monitoring. Different parameters of the method were evaluated, such as type of solid phase (C18, alumina, silica gel, and Florisil) and the amount of solid phase and eluent (dichloromethane, ethyl acetate, chloroform, and cyclohexane). The best results were obtained using 0.5 g herb sample, 0.5 g neutral alumina as the dispersant sorbent, 0.5 g C18 as the cleanup sorbent, and cyclohexane-dichloromethane (3 + 1, v/v) as the eluting solvent. The method was validated using herb samples fortified with pesticides at different concentration levels (0.3, 0.5, and 1.0 mg/kg). Average recoveries (seven replicates) ranged from 67.7 to 129.9%, with relative standard deviations between 6.3 and 26%. Detection and quantitation limits for the herb ranged from 0.10 to 0.15 and 0.15 to 0.25 mg/kg, respectively.

  3. Application of London-type dispersion corrections to the solid-state density functional theory simulation of the terahertz spectra of crystalline pharmaceuticals.

    Science.gov (United States)

    King, Matthew D; Buchanan, William D; Korter, Timothy M

    2011-03-14

    The effects of applying an empirical dispersion correction to solid-state density functional theory methods were evaluated in the simulation of the crystal structure and low-frequency (10 to 90 cm(-1)) terahertz spectrum of the non-steroidal anti-inflammatory drug, naproxen. The naproxen molecular crystal is bound largely by weak London force interactions, as well as by more prominent interactions such as hydrogen bonding, and thus serves as a good model for the assessment of the pair-wise dispersion correction term in systems influenced by intermolecular interactions of various strengths. Modifications to the dispersion parameters were tested in both fully optimized unit cell dimensions and those determined by X-ray crystallography, with subsequent simulations of the THz spectrum being performed. Use of the unmodified PBE density functional leads to an unrealistic expansion of the unit cell volume and the poor representation of the THz spectrum. Inclusion of a modified dispersion correction enabled a high-quality simulation of the THz spectrum and crystal structure of naproxen to be achieved without the need for artificially constraining the unit cell dimensions.

  4. Determination of twelve herbicides in tobacco by a combination of solid–liquid–solid dispersive extraction using multi-walled carbon nanotubes, dispersive liquid-liquid micro-extraction, and detection by GC with triple quadrupole mass spectrometry

    International Nuclear Information System (INIS)

    Liao, Qie Gen; Zhou, Yao Min; Luo, Lin Guang; Wang, Li Bing; Feng, Xiao Hu

    2014-01-01

    We report on a method for the determination of twelve herbicides using solid–liquid–solid dispersive extraction (SLSDE), followed by dispersive liquid-liquid micro-extraction (DLLME) and quantitation by gas chromatography with triple quadrupole mass spectrometric detection. SLSDE was applied to the extraction of herbicides from tobacco samples using multi-walled carbon nanotubes (MWCNTs) as clean-up adsorbents. The effect of the quantity of MWCNTs on SLSDE, and of type and volume of extraction and disperser solvents and of salt effect on DLLME were optimized. Good linearity is obtained in the 5.0 - 500 μg kg −1 concentration range, with regression coefficients of >0.99. Intra-day and inter-day repeatability, expressed as relative standard deviations, are between 3 and 9 %. The recoveries in case of herbicide-spiked tobacco at concentration levels of 20.0, 50.0 and 100.0 g kg −1 ranged from 79 to 105 %, and LODs are between 1.5 and 6.1 μg kg −1 . All the tobacco samples were found to contain butralin and pendimethalin at levels ranging from 15.8 to 500.0 μg kg −1 . (author)

  5. Facile solid-state synthesis of highly dispersed Cu nanospheres anchored on coal-based activated carbons as an efficient heterogeneous catalyst for the reduction of 4-nitrophenol

    Science.gov (United States)

    Wang, Shan; Gao, Shasha; Tang, Yakun; Wang, Lei; Jia, Dianzeng; Liu, Lang

    2018-04-01

    Coal-based activated carbons (AC) were acted as the support, Cu/AC catalysts were synthesized by a facile solid-state reaction combined with subsequent heat treatment. In Cu/AC composites, highly dispersed Cu nanospheres were anchored on AC. The catalytic activity for 4-nitrophenol (4-NP) was investigated, the effects of activation temperature and copper loading on the catalytic performance were studied. The catalysts exhibited very high catalytic activity and moderate chemical stability due to the unique characteristics of the particle-assembled nanostructures, the high surface area and the porous structure of coal-based AC and the good dispersion of metal particles. Design and preparation of non-noble metal composite catalysts provide a new direction for improving the added value of coal.

  6. Determination of the major constituents in fruit of Arctium lappa L. by matrix solid-phase dispersion extraction coupled with HPLC separation and fluorescence detection.

    Science.gov (United States)

    Liu, He; Zhang, Yupu; Sun, Yantao; Wang, Xue; Zhai, Yujuan; Sun, Ye; Sun, Shuo; Yu, Aimin; Zhang, Hanqi; Wang, Yinghua

    2010-10-15

    The arctiin and arctigenin in the fruit of Arctium lappa L. were extracted by matrix solid-phase dispersion (MSPD) and determined by high-performance liquid chromatography (HPLC) with fluorescence detection. The experimental conditions for the MSPD were optimized. Silica gel was selected as dispersion adsorbent and methanol as elution solvent. The calibration curve showed good relationship (r>0.9998) in the concentration range of 0.010-5.0μgmL(-1) for arctiin and 0.025-7.5μgmL(-1) for arctigenin. The recoveries were between 74.4% and 100%. The proposed method consumed less sample, time and solvent compared with conventional methods, including ultrasonic and Soxhlet extraction. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Application of dispersive liquid-liquid microextraction and dispersive micro-solid-phase extraction for the determination of quinolones in swine muscle by high-performance liquid chromatography with diode-array detection

    International Nuclear Information System (INIS)

    Tsai, Wen-Hsien; Chuang, Hung-Yi; Chen, Ho-Hsien; Huang, Joh-Jong; Chen, Hwi-Chang; Cheng, Shou-Hsun; Huang, Tzou-Chi

    2009-01-01

    Dispersive liquid-liquid microextraction (DLLME) and dispersive micro-solid-phase extraction (DMSPE) are two simple and low-cost sample preparation methods for liquid samples. In this work, these two methods were applied to solid tissue sample for the determination of seven quinolones by high-performance liquid chromatography with diode-array detection (HPLC-DAD). After the homogenization of the swine muscle with acetonitrile and salt-promoted partitioning, small amounts of the extract were used for the DLLME and DMSPE methods. In the DLLME approach, the target analytes in the extraction solvent were rapidly extracted into a small volume of dichloromethane for drying and the residue was reconstituted for HPLC-DAD analysis. In the DMSPE approach, the target analytes in the extraction solvent were trapped by dispersive silica-based PSA (primary and secondary amine) sorbents and desorbed into a small amount of desorption solution for HPLC-DAD analysis. Under the optimal conditions, relative recoveries were determined for swine muscle spiked 50-200 μg kg -1 and quantification was achieved by matrix-matched calibration. The calibration curves of seven quinolones showed linearity with a correlation coefficient value above 0.998 for both approaches. Relative recoveries ranged from 93.0 to 104.7% and from 95.5 to 111.0% for DLLME and DMSPE, respectively. Limits of detection (LODs) ranged from 5.6 to 23.8 μg kg -1 and from 7.5 to 26.3 μg kg -1 for DLLME and DMSPE, respectively.

  8. Amorphous metal composites

    International Nuclear Information System (INIS)

    Byrne, M.A.; Lupinski, J.H.

    1984-01-01

    This patent discloses an improved amorphous metal composite and process of making the composite. The amorphous metal composite comprises amorphous metal (e.g. iron) and a low molecular weight thermosetting polymer binder. The process comprises placing an amorphous metal in particulate form and a thermosetting polymer binder powder into a container, mixing these materials, and applying heat and pressure to convert the mixture into an amorphous metal composite

  9. Enhancement of solubility and oral bioavailability of manidipine by formation of ternary solid dispersion with d-α-tocopherol polyethylene glycol 1000 succinate and copovidone.

    Science.gov (United States)

    Chamsai, Benchawan; Limmatvapirat, Sontaya; Sungthongjeen, Srisagul; Sriamornsak, Pornsak

    2017-12-01

    Low bioavailability of oral manidipine (MDP) is due to its low water solubility. The objective of this study was to increase the solubility and bioavailability of MDP by fabricating ternary solid dispersion (tSD) with d-α-tocopherol polyethyleneglycol-1000-succinate and copovidone. In this study, solid ternary phase diagram was applied in order to check the homogeneity of tSD prepared by melting and solidifying with dry ice. The physicochemical properties of different formulations were determined by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR) and hot stage microscopy. Their solubility, dissolution, stability and bioavailability were also investigated. The results demonstrated that tSD obtained from ternary phase diagram divided into homogeneous and non-homogeneous regions. In the homogenous region, the transparent characteristics of tSD was observed and considered as a glass solution, which have a higher MDP solubility than that in non-homogenous region. The hot stage microscopy, DSC and PXRD confirmed that solid dispersion was formed in which MDP was molecularly dispersed in the carriers, especially in the homogenous region of phase diagram. FTIR analysis demonstrated strong hydrogen bonding between amine groups of MDP and carbonyl groups of copovidone, which supported a higher solubility and dissolution of tSD. The pharmacokinetic study in Wistar rats showed that the tSD had the greatest effect on oral bioavailability. Immediate hypotensive effect of tSD was also observed in vivo. The improvement of stability, dissolution and oral bioavailability of MDP could be achieved by using tSD technique.

  10. Recovery evaluation of organophosphorus pesticides from bee pollen by matrix solid-phase dispersion extraction using sorbents based on silica and titania

    International Nuclear Information System (INIS)

    Torres-Perea, C; Muñoz-Rodríguez, D; Carrera-Figueiras, C; Medina-Peralta, S; Moguel-Ordóñez, Y B

    2013-01-01

    This work focused on the evaluation of the recovery of organophosphorus pesticides from bee pollen after matrix solid phase-dispersion extraction (MSPD). Materials based on silica, titania and titania modified with polivylnylimidazole or polyestirene were used as adsorbents for the extraction of pesticides. Small amounts of fortified pollen (0.1 g, at 1 micro-g/g of pesticides), adsorbent (0.4 g) and solvent elution (1 mL de acetonitrile – ACN) were used in the extractions. For recovery evaluation, pollen extracts were analyzed by gas chromatography coupled with mass spectrometry.

  11. Concentration of organic compounds in natural waters with solid-phase dispersion based on advesicle modified silica prior to liquid chromatography.

    Science.gov (United States)

    Parisis, Nikolaos A; Giokas, Dimosthenis L; Vlessidis, Athanasios G; Evmiridis, Nicholaos P

    2005-12-02

    The ability of vesicle-coated silica to aid the extraction of organic compounds from water prior to liquid chromatographic analysis is presented for the first time. The method is based on the formation of silica supported cationic multi-lamellar vesicles of gemini surfactants inherently ensuring the presence of hydrophilic and hydrophobic sites for the partitioning of analytes bearing different properties. Method development is illustrated by studying the adsolubilization of UV absorbing chemicals from swimming pool water. Due to the requirement for external energy input (intense shearing) a method based on solid-phase dispersion (SPD) was applied producing better results than off-line solid-phase extraction (SPE). Meticulous investigation of the experimental parameters was conducted in order to elucidate the mechanisms behind the proposed extraction pattern. Analyte recoveries were quantitative under the optimum experimental conditions offering recoveries higher than 96% with RSD values below 5%.

  12. Structural characterization of the phospholipid stabilizer layer at the solid-liquid interface of dispersed triglyceride nanocrystals with small-angle x-ray and neutron scattering

    Science.gov (United States)

    Schmiele, Martin; Schindler, Torben; Unruh, Tobias; Busch, Sebastian; Morhenn, Humphrey; Westermann, Martin; Steiniger, Frank; Radulescu, Aurel; Lindner, Peter; Schweins, Ralf; Boesecke, Peter

    2013-06-01

    Dispersions of crystalline nanoparticles with at least one sufficiently large unit cell dimension can give rise to Bragg reflections in the small-angle scattering range. If the nanocrystals possess only a small number of unit cells along these particular crystallographic directions, the corresponding Bragg reflections will be broadened. In a previous study of phospholipid stabilized dispersions of β-tripalmitin platelets [Unruh, J. Appl. Crystallogr.JACGAR0021-889810.1107/S0021889807044378 40, 1008 (2007)], the x-ray powder pattern simulation analysis (XPPSA) was developed. The XPPSA method facilitates the interpretation of the rather complicated small-angle x-ray scattering (SAXS) curves of such dispersions of nanocrystals. The XPPSA method yields the distribution function of the platelet thicknesses and facilitates a structural characterization of the phospholipid stabilizer layer at the solid-liquid interface between the nanocrystals and the dispersion medium from the shape of the broadened 001 Bragg reflection. In this contribution an improved and extended version of the XPPSA method is presented. The SAXS and small-angle neutron scattering patterns of dilute phospholipid stabilized tripalmitin dispersions can be reproduced on the basis of a consistent simulation model for the particles and their phospholipid stabilizer layer on an absolute scale. The results indicate a surprisingly flat arrangement of the phospholipid molecules in the stabilizer layer with a total thickness of only 12 Å. The stabilizer layer can be modeled by an inner shell for the fatty acid chains and an outer shell including the head groups and additional water. The experiments support a dense packing of the phospholipid molecules on the nanocrystal surfaces rather than isolated phospholipid domains.

  13. Axial Dispersion Model for Solid Flow in Liquid Suspension in System of Two Mixers in Total Recycle

    Czech Academy of Sciences Publication Activity Database

    Čermáková, Jiřina; Scargiali, F.; Siyakatshana, N.; Kudrna, V.; Brucato, A.; Machoň, V.

    2006-01-01

    Roč. 117, č. 2 (2006), s. 101-107 ISSN 1385-8947 R&D Projects: GA AV ČR(CZ) IAA4072402 Institutional research plan: CEZ:AV0Z40720504 Keywords : residence time distribution * dispersion model * flow mixer Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 1.594, year: 2006

  14. Cellulose nanocrystal/polyolefin biocomposites prepared by solid-state shear pulverization: Superior dispersion leading to synergistic property enhancements

    Science.gov (United States)

    Krishnan A. Iyer; Gregory T. Schueneman; John M. Torkelson

    2015-01-01

    Cellulose nanocrystals (CNCs), a class of renewable bionanomaterials with excellent mechanical properties, have gained major interest as filler for polymers. However, challenges associated with effective CNC dispersion have hindered the production of composites with desired property enhancements. Here, composites of polypropylene (PP) and low density polyethylene (LDPE...

  15. Use of acidifier and solubilizer in tadalafil solid dispersion to enhance the in vitro dissolution and oral bioavailability in rats.

    Science.gov (United States)

    Choi, Jin-Seok; Kwon, Soon-Hyung; Lee, Sang-Eun; Jang, Woo Suk; Byeon, Jong Chan; Jeong, Hyeong Mo; Park, Jeong-Sook

    2017-06-30

    The purpose of this study is to improve the solubility, in vitro dissolution, and oral bioavailability in rats of tadalafil (TDF) by using SD technique with a weak acid and a copolymer. TDF-SD was prepared via solvent evaporation, coupled with the incorporation of an acidifier and solubilizer. Tartaric acid enhanced the solubility of TDF over 5-fold in DW, and Soluplus ® enhanced the solubility of TDF over 8.7-fold and 19.2-fold compared to that of TDF (pure) in DW and pH 1.2 for 1h, respectively. The optimal formulation of TDF-SD3 was composed of TDF vs Tartaric acid vs Soluplus ® vs Aerosil=1:1:3:3. The in vitro dissolution rate of TDF-SD3 in DW, pH 1.2 and pH 6.8 buffer (51.5%, 53.3%, and 33.2%, respectively) was significantly higher than that of the commercial product (Cialis ® ) powder (16.5%, 15.2%, and 14.8%, respectively). TDF was completely transformed to an amorphous form as shown in SEM, DSC and PXRD data. The stability of TDF-SD3 included drug contents and in vitro dissolution for 1 month were similar to those of Cialis ® , and the amorphous form of TDF-SD3 was well maintained for 6 months. The TDF-SD3 formulation improved the relative bioavailability (BA) and peak plasma concentration (C max ) compared to that of Cialis ® powder after oral administration in rats as 117.3% and 135.7%, respectively. From the results, we found that the acidifier increased the wettability of TDF, and the solubilizer improved solubility through hydrogen bonding with TDF, thereby increasing the solubility, dissolution and oral bioavailability of TDF in TDF-SD3. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Physisorption and desorption of H2, HD and D2 on amorphous solid water ice. Effect on mixing isotopologue on statistical population of adsorption sites.

    Science.gov (United States)

    Amiaud, Lionel; Fillion, Jean-Hugues; Dulieu, François; Momeni, Anouchah; Lemaire, Jean-Louis

    2015-11-28

    We study the adsorption and desorption of three isotopologues of molecular hydrogen mixed on 10 ML of porous amorphous water ice (ASW) deposited at 10 K. Thermally programmed desorption (TPD) of H2, D2 and HD adsorbed at 10 K have been performed with different mixings. Various coverages of H2, HD and D2 have been explored and a model taking into account all species adsorbed on the surface is presented in detail. The model we propose allows to extract the parameters required to fully reproduce the desorption of H2, HD and D2 for various coverages and mixtures in the sub-monolayer regime. The model is based on a statistical description of the process in a grand-canonical ensemble where adsorbed molecules are described following a Fermi-Dirac distribution.

  17. Application of a Salt Coformer in a Co-Amorphous Drug System Dramatically Enhances the Glass Transition Temperature: A Case Study of the Ternary System Carbamazepine, Citric Acid, and l-Arginine.

    Science.gov (United States)

    Ueda, Hiroshi; Wu, Wenqi; Löbmann, Korbinian; Grohganz, Holger; Müllertz, Anette; Rades, Thomas

    2018-04-13

    The use of co-amorphous systems containing a combination of low molecular weight drugs and excipients is a relatively new technology in the pharmaceutical field to improve the solubility of poorly water-soluble drugs. However, some co-amorphous systems show a lower glass transition temperature ( T g ) than many of their polymeric solid dispersion counterparts. In this study, we aimed at designing a stable co-amorphous system with an elevated T g . Carbamazepine (CBM) and citric acid (CA) were employed as the model drug and the coformer, respectively. co-amorphous CBM-CA at a 1:1 molar ratio was formed by ball milling, but a transition from the glassy to the supercooled melt state was observed under ambient conditions, due to the relatively low T g of 38.8 °C of the co-amorphous system and moisture absorption. To improve the T g of the coformer, salt formation of a combination of l-arginine (ARG) with CA was studied. First, ball milling of CA-ARG at molar ratios of 1:1, 1:2, and 1:3 forming co-amorphous systems was performed and led to a dramatic enhancement of the T g , depending on the CA-ARG ratio. Salt formation between CA and ARG was observed by infrared spectroscopy. Next, ball milling of CBM-CA-ARG at molar ratios of 1:1:1, 1:1:2, and 1:1:3 resulted in co-amorphous blends, which had a single T g at 77.8, 105.3, and 127.8 °C, respectively. These ternary co-amorphous samples remained in a solid amorphous form for 2 months at 40 °C. From these results, it can be concluded that blending of the salt coformer with a drug is a promising strategy to design stable co-amorphous formulations.

  18. Molecular-level elucidation of saccharin-assisted rapid dissolution and high supersaturation level of drug from Eudragit® E solid dispersion.

    Science.gov (United States)

    Ueda, Keisuke; Kanaya, Harunobu; Higashi, Kenjirou; Yamamoto, Keiji; Moribe, Kunikazu

    2018-03-01

    In this work, the effect of saccharin (SAC) addition on the dissolution and supersaturation level of phenytoin (PHT)/Eudragit® E (EUD-E) solid dispersion (SD) at neutral pH was examined. The PHT/EUD-E SD showed a much slower dissolution of PHT compared to the PHT/EUD-E/SAC SD. EUD-E formed a gel layer after the dispersion of the PHT/EUD-E SD into an aqueous medium, resulting in a slow dissolution of PHT. Pre-dissolving SAC in the aqueous medium significantly improved the dissolution of the PHT/EUD-E SD. Solid-state 13 C NMR measurements showed an ionic interaction between the tertiary amino group of EUD-E and the amide group of SAC in the EUD-E gel layer. Consequently, the ionized EUD-E could easily dissolve from the gel layer, promoting PHT dissolution. Solution-state 1 H NMR measurements revealed the presence of ionic interactions between SAC and the amino group of EUD-E in the PHT/EUD-E/SAC solution. In contrast, interactions between PHT and the hydrophobic group of EUD-E strongly inhibited the crystallization of the former from its supersaturated solution. The PHT supersaturated solution was formed from the PHT/EUD-E/SAC SD by the fast dissolution of PHT and the strong crystallization inhibition effect of EUD-E after aqueous dissolution. Copyright © 2018 Elsevier B.V. All rights reserved.

  19. Fabrication of a novel hydrophobic/ion-exchange mixed-mode adsorbent for the dispersive solid-phase extraction of chlorophenols from environmental water samples.

    Science.gov (United States)

    Gao, Li; Wei, Yinmao

    2016-08-01

    A novel mixed-mode adsorbent was prepared by functionalizing silica with tris(2-aminoethyl)amine and 3-phenoxybenzaldehyde as the main mixed-mode scaffold due to the presence of the plentiful amino groups and benzene rings in their molecules. The adsorption mechanism was probed with acidic, natural and basic compounds, and the mixed hydrophobic and ion-exchange interactions were found to be responsible for the adsorption of analytes. The suitability of dispersive solid-phase extraction was demonstrated in the determination of chlorophenols in environmental water. Several parameters, including sample pH, desorption solvent, ionic strength, adsorbent dose, and extraction time were optimized. Under the optimal extraction conditions, the proposed dispersive solid-phase extraction coupled with high-performance liquid chromatography showed good linearity range and acceptable limits of detection (0.22∽0.54 ng/mL) for five chlorophenols. Notably, the higher extraction recoveries (88.7∽109.7%) for five chlorophenols were obtained with smaller adsorbent dose (10 mg) and shorter extraction time (15 min) compared with the reported methods. The proposed method might be potentially applied in the determination of trace chlorophenols in real water samples. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  20. Solid-phase extraction assisted dispersive liquid-liquid microextraction based on solidification of floating organic droplet to determine sildenafil and its analogues in dietary supplements.

    Science.gov (United States)

    Li, Jing; Roh, Si Hun; Shaodong, Jia; Hong, Ji Yeon; Lee, Dong-Kyu; Shin, Byong-Kyu; Park, Jeong Hill; Lee, Jeongmi; Kwon, Sung Won

    2017-08-01

    A novel analytical method for the simultaneous determination of the concentration of sildenafil and its five analogues in dietary supplements using solid-phase extraction assisted reversed-phase dispersive liquid-liquid microextraction based on solidification of floating organic droplet combined with ion-pairing liquid chromatography with an ultraviolet detector was developed. Parameters that affect extraction efficiency were systematically investigated, including the type of solid-phase extraction cartridge, pH of the extraction environment, and the type and volume of extraction and dispersive solvent. The method linearity was in the range of 5.0-100 ng/mL for sildenafil, homosildenafil, udenafil, benzylsildenafil, and thiosildenafil and 10-100 ng/mL for acetildenafil. The coefficients of determination were ≥0.996 for all regression curves. The sensitivity values expressed as limit of detection were between 2.5 and 7.5 ng/mL. Furthermore, intraday and interday precisions expressed as relative standard deviations were less than 5.7 and 9.9%, respectively. The proposed method was successfully applied to the analysis of sildenafil and its five analogues in complex dietary supplements. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Matrix solid-phase dispersion followed by gas chromatography tandem mass spectrometry for the determination of benzotriazole UV absorbers in sediments.

    Science.gov (United States)

    Carpinteiro, I; Abuín, B; Ramil, M; Rodríguez, I; Cela, R

    2012-01-01

    A cost-effective and low solvent consumption method, based on the matrix solid-phase dispersion (MSPD) technique, for the determination of six benzotriazole UV absorbers in sediments is presented. Sieved samples (0.5 g) were first mixed in a mortar with a solid sorbent and then transferred to a polypropylene syringe containing a layer of clean-up co-sorbent. Analytes were eluted with a suitable solvent and further determined by gas chromatography with tandem mass spectrometry (GC-MS/MS). Under final conditions, diatomaceous earth and silica, deactivated to 10%, were used as inert dispersant and clean-up co-sorbent, respectively. Analytes were recovered using just 5 mL of dichloromethane, and this extract was concentrated and exchanged to 1 mL of isooctane. Further removal of co-extracted sulphur was achieved adding activated copper powder to final extracts, which were stored overnight, before injection in the GC-MS/MS system. The accuracy of the method was assessed with river and marine sediment samples showing different carbon contents and spiked at different concentrations in the range from 40 to 500 ng g(-1). Recoveries varied between 78% and 110% with associated standard deviations below 14%. The limits of quantification of the method stayed between 3 and 15 ng g(-1). Levels of target compounds in sediment samples ranged from not detected up to a maximum of 56 ng g(-1) for Tinuvin 328.

  2. Vortex-Assisted Dispersive Micro-Solid Phase Extraction Using CTAB-Modified Zeolite NaY Sorbent Coupled with HPLC for the Determination of Carbamate Insecticides.

    Science.gov (United States)

    Salisaeng, Pawina; Arnnok, Prapha; Patdhanagul, Nopbhasinthu; Burakham, Rodjana

    2016-03-16

    A vortex-assisted dispersive micro-solid phase extraction (VA-D-μ-SPE) based on cetyltrimethylammonium bromide (CTAB)-modified zeolite NaY was developed for preconcentration of carbamate pesticides in fruits, vegetables, and natural surface water prior to analysis by high performance liquid chromatography with photodiode array detection. The small amounts of solid sorbent were dispersed in a sample solution, and extraction occurred by adsorption in a short time, which was accelerated by vortex agitation. Finally, the sorbents were filtered from the solution, and the analytes were subsequently desorbed using an appropriate solvent. Parameters affecting the VA-D-μ-SPE performance including sorbent amount, sample volume, desorption solvent ,and vortex time were optimized. Under the optimum condition, linear dynamic ranges were achieved between 0.004-24.000 mg kg(-1) (R(2) > 0.9946). The limits of detection (LODs) ranged from 0.004-4.000 mg kg(-1). The applicability of the developed procedure was successfully evaluated by the determination of the carbamate residues in fruits (dragon fruit, rambutan, and watermelon), vegetables (cabbage, cauliflower, and cucumber), and natural surface water.

  3. Optimization of matrix solid-phase dispersion for the rapid determination of salicylate and benzophenone-type UV absorbing substances in marketed fish.

    Science.gov (United States)

    Tsai, Dung-Ying; Chen, Chien-Liang; Ding, Wang-Hsien

    2014-07-01

    A simple and effective method for the rapid determination of five salicylate and benzophenone-type UV absorbing substances in marketed fish is described. The method involves the use of matrix solid-phase dispersion (MSPD) prior to their determination by on-line silylation gas chromatography tandem mass spectrometry (GC-MS/MS). The parameters that affect the extraction efficiency were optimized using a Box-Behnken design method. The optimal extraction conditions involved dispersing 0.5g of freeze-dried powdered fish with 1.0g of Florisil using a mortar and pestle. This blend was then transferred to a solid-phase extraction (SPE) cartridge containing 1.0g of octadecyl bonded silica (C18), as the clean-up co-sorbent. The target analytes were then eluted with 7mL of acetonitrile. The extract was derivatized on-line in the GC injection-port by reaction with a trimethylsilylating (TMS) reagent. The TMS-derivatives were then identified and quantitated by GC-MS/MS. The limits of quantitation (LOQs) were less than 0.1ng/g. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Development of a Matrix Solid-Phase Dispersion Extraction Combined with UPLC/Q-TOF-MS for Determination of Phenolics and Terpenoids from the Euphorbia fischeriana.

    Science.gov (United States)

    Li, Wenjing; Lin, Yu; Wang, Yuchun; Hong, Bo

    2017-09-11

    A method based on a simplified extraction by matrix solid phase dispersion (MSPD) followed by ultra-performance liquid chromatography coupled with the quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF-MS) determination is validated for analysis of two phenolics and three terpenoids in Euphorbia fischeriana . The optimized experimental parameters of MSPD including dispersing sorbent (silica gel), ratio of sample to dispersing sorbent (1:2), elution solvent (water-ethanol: 30-70) and volume of the elution solvent (10 mL) were examined and set down. The highest extraction yields of chromatogram information and the five compounds were obtained under the optimized conditions. A total of 25 constituents have been identified and five components have been quantified from Euphorbia fischeriana . A linear relationship (r² ≥ 0.9964) between the concentrations and the peak areas of the mixed standard substances were revealed. The average recovery was between 92.4% and 103.2% with RSD values less than 3.45% ( n = 5). The extraction yields of two phenolics and three terpenoids obtained by the MSPD were higher than those of traditional reflux and sonication extraction with reduced requirement on sample, solvent and time. In addition, the optimized method will be applied for analyzing terpenoids in other Chinese herbal medicine samples.

  5. Dispersive solid phase micro-extraction of mercury(II from environmental water and vegetable samples with ionic liquid modified graphene oxide nanoparticles

    Directory of Open Access Journals (Sweden)

    Nasrollahpour Atefeh

    2017-01-01

    Full Text Available A new dispersive solid phase micro-extraction (dispersive-SPME method for separation and preconcentration of mercury(II using ionic liquid modified magnetic reduced graphene oxide (IL-MrGO nanoparticles, prior to the measurement by cold vapour atomic absorption spectrometry (CV-AAS has been developed. The IL-MrGO composite was characterized by Brunauer– Emmett–Teller method (BET for adsorption-desorption measurement, thermogravimetric analysis (TGA, powder X-ray diffraction (XRD and X-ray photoelectron spectroscopy (XPS. The method is based on the sorption of mercury( II on IL-MrGO nanoparticles due to electrostatic interaction and complex formation of ionic liquid part of IL-MrGO with mercury(II. The effect of experimental parameters for preconcentration of mercury(II, such as solution type, concentration and volume of the eluent, pH, time of the sorption and desorption, amount of the sorbent and coexisting ion concentration have been optimized. Under the optimized conditions, a linear response was obtained in the concentration range of 0.08–10 ng mL-1 with a determination coefficient of 0.9995. The limit of detection (LOD of the method at a signal to noise ratio of 3 was 0.01 ng mL-1. Intra-day and inter-day precisions were obtained equal to 3.4 and 4.5 %, respectively. The dispersive solid phase micro-extraction of mercury(II on IL-MrGO nanoparticles coupled with cold vapour atomic absorption spectrometry was successfully used for extraction and determination of mercury(II in water and vegetable samples.

  6. In-line micro-matrix solid-phase dispersion extraction for simultaneous separation and extraction of Sudan dyes in different spices.

    Science.gov (United States)

    Rajabi, Maryam; Sabzalian, Sedigheh; Barfi, Behruz; Arghavani-Beydokhti, Somayeh; Asghari, Alireza

    2015-12-18

    A novel, simple, fast, and miniaturized method, termed in-line micro-matrix solid-phase dispersion (in-line MMSPD), coupled with high performance liquid chromatography (HPLC) was developed for the simultaneous extraction and determination of Sudan dyes (i.e. Sudan I-IV, Sudan orange G, Sudan black B, and Sudan red G) with the aid of an experimental design strategy. In this method, a matrix solid-phase dispersion (MSPD) column including a suitable mixture of polar sorbents was inserted in the mobile phase pathway, and while the interfering compounds were retained, the analytes were eluted and entered into the analytical column. In this way, the extraction, elution, and separation of the analytes were performed sequentially. Under the optimal experimental conditions (including the amount of sample, 0.0426g; amount of dispersant phase, 0.0216g of florisil, 0.0227g of silica, 0.0141g of alumina; and blending time, 112s), the limits of detection (LODs), limits of quantification, linear dynamic ranges, and recoveries were obtained to be 0.3-15.3μgkg(-1), 1-50μgkg(-1), 50-28,000μgkg(-1), and 94.5-99.1%, respectively. The results obtained showed that determination of the selected Sudan dyes in food samples using an enough sensitive and a simple analytically validated method like in-line MMSPD may offer a suitable screening method, which could be useful for food analysis and adulteration. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Formation of amorphous layers by irradiation

    International Nuclear Information System (INIS)

    Bourgoin, J.C.

    1979-01-01

    When an ordered solid is irradiated with heavy energy particles, disorder is produced. When the irradiation dose exceeds a so-called critical dose, the irradiated area of the solid becomes uniformly disordered. Mention is first made of the nature, concentration and distribution of the defects created by a heavy energy particle. The description is then given -solely with respect to semiconductors- of the effect of the various parameters on the critical dose energy and nature of the ion, nature and temperature of the solid, irradiation flux. The physical properties (electronic and thermodynamic types) and the uniformly disordered areas are briefly discussed and these properties are compared with those of amorphous semiconductor layers fabricated by evaporation. It is concluded that the evaporated and irradiated layers are similar in nature. It is suggested that the transformation of an irradiated crystalline area into an amorphous one occurs when the Gibbs energy of the crystal become greater than the Gibbs energy of the amorphous one [fr

  8. Preconcentration of Trace Neonicotinoid Insecticide Residues Using Vortex-Assisted Dispersive Micro Solid-Phase Extraction with Montmorillonite as an Efficient Sorbent

    Directory of Open Access Journals (Sweden)

    Khwankaew Moyakao

    2018-04-01

    Full Text Available In this work, we investigated montmorillonite for adsorption of neonicotinoid insecticides in vortex-assisted dispersive micro-solid phase extraction (VA-d-μ-SPE. High-performance liquid chromatography with photodiode array detection was used for quantification and determination of neonicotinoid insecticide residues, including thiamethoxam, clothianidin, imidacloprid, acetamiprid, and thiacloprid. In this method, the solid sorbent was dispersed into the aqueous sample solution and vortex agitation was performed to accelerate the extraction process. Finally, the solution was filtered from the solid sorbent with a membrane filter. The parameters affecting the extraction efficiency of the proposed method were optimized, such as amount of sorbent, sample volume, salt addition, type and volume of extraction solvent, and vortex time. The adsorbing results show that montmorillonite could be reused at least 4 times and be used as an effective adsorbent for rapid extraction/preconcentration of neonicotinoid insecticide residues. Under optimum conditions, linear dynamic ranges were achieved between 0.5 and 1000 ng mL−1 with a correlation of determination (R2 greater than 0.99. Limit of detection (LOD ranged from 0.005 to 0.065 ng mL−1, while limit of quantification (LOQ ranged from 0.008 to 0.263 ng mL−1. The enrichment factor (EF ranged from 8 to 176-fold. The results demonstrated that the proposed method not only provided a more simple and sensitive method, but also can be used as a powerful alternative method for the simultaneous determination of insecticide residues in natural surface water and fruit juice samples.

  9. A guide to and review of the use of Multiwavelength Raman Spectroscopy for characterizing defective aromatic carbon solids : From graphene to amorphous carbons

    NARCIS (Netherlands)

    Merlen, A.; Buijnsters, J.G.; Pardanaud, C.

    2017-01-01

    sp2 hybridized carbons constitute a broad class of solid phases composed primarily of elemental carbon and can be either synthetic or naturally occurring. Some examples are graphite, chars, soot, graphene, carbon nanotubes, pyrolytic carbon, and diamond-like carbon. They vary from highly ordered to

  10. Surface Passivation of CdSe Quantum Dots in All Inorganic Amorphous Solid by Forming Cd1-xZnxSe Shell.

    Science.gov (United States)

    Xia, Mengling; Liu, Chao; Zhao, Zhiyong; Wang, Jing; Lin, Changgui; Xu, Yinsheng; Heo, Jong; Dai, Shixun; Han, Jianjun; Zhao, Xiujian

    2017-02-07

    CdSe quantum dots (QDs) doped glasses have been widely investigated for optical filters, LED color converter and other optical emitters. Unlike CdSe QDs in solution, it is difficult to passivate the surface defects of CdSe QDs in glass matrix, which strongly suppress its intrinsic emission. In this study, surface passivation of CdSe quantum dots (QDs) by Cd 1-x Zn x Se shell in silicate glass was reported. An increase in the Se/Cd ratio can lead to the partial passivation of the surface states and appearance of the intrinsic emission of CdSe QDs. Optimizing the heat-treatment condition promotes the incorporation of Zn into CdSe QDs and results in the quenching of the defect emission. Formation of CdSe/Cd 1-x Zn x Se core/graded shell QDs is evidenced by the experimental results of TEM and Raman spectroscopy. Realization of the surface passivation and intrinsic emission of II-VI QDs may facilitate the wide applications of QDs doped all inorganic amorphous materials.

  11. Rayleigh Wave Dispersion Due to Spatial (FEM) Discretization of a thin Elastic Solid Having Non-Curved Boundary

    Czech Academy of Sciences Publication Activity Database

    Brepta, R.; Valeš, F.; Červ, Jan; Tikal, B.

    1996-01-01

    Roč. 58, č. 6 (1996), s. 1233-1244 ISSN 0045-7949 R&D Projects: GA ČR(CZ) GA101/93/1195 Institutional research plan: CEZ:AV0Z2076919 Keywords : thin elastic body * Rayleigh waves * grid dispersion Subject RIV: BI - Acoustics Impact factor: 0.254, year: 1996 http://apps.isiknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=1&SID=U2EJknka3H@mKemE37@&page=1&doc=1&colname=WOS

  12. Design of sustained-release nitrendipine microspheres having solid dispersion structure by quasi-emulsion solvent diffusion method

    DEFF Research Database (Denmark)

    Cui, Fude; Yang, Mingshi; Jiang, Yanyan

    2003-01-01

    crystallization technique, i.e. quasi-emulsion solvent diffusion method. The factors of effect on micromeritic properties and release profiles of the resultant microspheres were investigated. And the bioavailability of nitrendipine microspheres was evaluated in six healthy dogs. The results showed...... that the particle size of microspheres was determined mainly by the agitation speed. The dissolution rate of nitrendipine from microspheres was enhanced significantly with increasing the amount of dispersing agents, and sustained by adding retarding agents. The release rate of microspheres could be controlled...