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Sökning: L773:0022 3549 OR L773:1520 6017 > (2000-2009)

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1.
  • Bengtsson, Jörgen, et al. (författare)
  • The use of a deuterated calibrator for in vivo recovery estimations in microdialysis studies
  • 2008
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 97:8, s. 3433-3441
  • Tidskriftsartikel (refereegranskat)abstract
    • One of the crucial issues in quantitative microdialysis is the reliability of recovery estimates to correctly estimate unbound drug tissue concentrations. If a deuterated calibrator is used for retrodialysis, the calibrator has the same properties as the study drug. However, recovery of the calibrator may be affected by the presence of the drug in the tissues. The aim of this study was to investigate the recovery of deuterated morphine with time in the absence and presence of morphine in rat tissues. Microdialysis probes were placed in the brain and blood of eight rats. Ringer's solution containing D3-morphine was perfused throughout the study and recovery was estimated. After a stabilization period of 3 h, an exponential infusion of morphine was administered over 4 h. The presence of morphine did not affect the recovery of D3-morphine from brain or blood. The average recovery values (SD) were 0.145 (0.039) and 0.131 (0.048) during the stabilization and infusion periods, respectively, for the brain probe and 0.792 (0.055) and 0.790 (0.084), respectively, for the blood probe. The recovery of deuterated morphine was stable over time in the brain and in blood, and was not affected by the presence of pharmacologically concentrations of morphine.
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2.
  • Bergstrom, P. O., et al. (författare)
  • Crystal structure and physical properties of two polymorphs of ropivacaine HCl
  • 2006
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 95:3, s. 680-688
  • Tidskriftsartikel (refereegranskat)abstract
    • The crystal structure of two polymorphs of ropivacaine HCl have been determined, as well as their relative stability up to 100 degrees C. A geometric restriction for a solid-state transition between the two polymorphs has been identified. The packing density along the H-bonded chains form the basis for a model explaining the kinetic crystallization of the metastable form. The difference in stability and physicochemical properties between the two polymorphs can be attributed to the difference in crystal structure.
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4.
  • Boström, Emma, et al. (författare)
  • Oxycodone Pharmacokinetics and Pharmacodynamics in the Rat in the Presence of the P-Glycoprotein Inhibitor PSC833
  • 2005
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 94:5, s. 1060-1066
  • Tidskriftsartikel (refereegranskat)abstract
    • The objective of this study was to investigate the in vivo influence of the P-glycoprotein (P-gp) inhibitor PSC833 on the plasma pharmacokinetics, total brain concentrations and tail-flick latency of oxycodone in rats. Eight rats each received an infusion of PSC833 or vehicle without PSC833. One hour later, all animals received 0.3 mg/kg oxycodone as a 1-h infusion. Plasma samples were taken, and tail-flick latency was monitored during the infusion and for 2 h thereafter. The brains were collected at the end of the experiment. There were no differences between the two groups in area under the plasma oxycodone concentration-time curve from time zero to infinity, or oxycodone plasma clearance, volume of distribution at steady-state, or half-life. There were no differences in average total brain oxycodone concentrations at 180 min, nor were there any differences in average tail-flick latency for the PSC833 and control groups. In conclusion, coadministration of PSC833 did not alter the plasma pharmacokinetics, brain concentrations, or associated tail-flick latency of oxycodone, indicating that oxycodone is not a P-gp substrate in the rat. This has important clinical implications, as it indicates that oxycodone, unlike some other opioids, will not interact at the blood-brain barrier (BBB) with concomitantly administered P-gp substrates.
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5.
  • Brohede, Ulrika, et al. (författare)
  • Characterization of the drug release process by investigation of its temperature dependence
  • 2004
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 93:7, s. 1796-1803
  • Tidskriftsartikel (refereegranskat)abstract
    • Temperature-dependent drug release from disintegrating tablets made of NaCl-containing agglomerated micronized cellulose (AMC) granules has been studied to characterize the release process. Release measurements on tablets compacted at three different compaction pressures; 50, 100, and 200 MPa, were performed at seven different temperatures; 6, 23, 33, 43, 50, 55, and 63°C using the recently developed alternating ionic current method. Tablets compacted at different compaction pressures showed similar release rates. The release process was found to be diffusion-controlled, and the activation energy of the diffusion coefficient was comparable to that obtained for diffusion in pure water. The results show that the AMC granules in contact with water swell to a size and shape that is only slightly affected by their compaction history and the ion diffusion operates mainly within liquid-filled pores within the AMC granules. By using the temperature dependence of the release process, it was possible to reach this conclusion without any assumptions concerning the number and radii of the granules into which the tablets disintegrated. Further, the magnitude of the effective diffusion coefficient was found to be ∼7.5 · 10−10 cm2/s, which is ∼four orders of magnitude lower than for unhindered diffusion of Na+ and Cl− in water but similar to the diffusion coefficient for protons and OH− ions in microcrystalline cellulose.
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6.
  • Brohede, Ulrika, et al. (författare)
  • Percolative drug diffusion from cylindrical matrix systems with unsealed boundaries
  • 2007
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 96:11, s. 3087-3099
  • Tidskriftsartikel (refereegranskat)abstract
    • Release of NaCl in both the axial and radial directions from cylindrical ethyl cellulose tablets were investigated by the alternating ionic current method. The pore structure of the investigated binary mixtures was examined by mercury porosimetry and scanning electron microscopy, and the nm range fractal surface dimension of tablet pore walls was extracted from krypton gas adsorption isotherms. The drug release was shown to consist of two overlapping processes of which the first was ascribed to dissolution of NaCl close to the tablet boundary followed by subsequent diffusion through a thin ethyl cellulose layer and a second from which a porosity percolation threshold of 0.22 could be extracted. As well, a cross-over to effective-medium behaviour at a porosity of 0.44 was observed. The presented findings showed that drug release from matrix tablets with unsealed tablet walls substantially differs from earlier investigated release processes for which the drug has only been allowed to escape through one of the flat tablet surfaces. Thus, the present study brings forward knowledge important for the tailoring of controlled drug delivery vehicles with optimum release patterns.
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7.
  • Elversson, Jessica, et al. (författare)
  • An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles
  • 2007
  • Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 96:4, s. 905-912
  • Tidskriftsartikel (refereegranskat)abstract
    • To evaluate an atomic force microscopy (A-FM) approach for effective density analysis of single spray dried carbohydrate particles in order to investigate the internal structure of the particles. In addition, the AFM method was compared to an established technique, that is gas pycnometry. Resonant frequency AFM analysis was employed for determination of the mass of individual particles of spray-dried lactose, mannitol, and a mixture of sucrose/dextran (4:1). The effective particle density was calculated using the diameter of the spherical particles obtained from light microscopy. The apparent particle density was further analyzed with gas pycnometry. It was observed by microscopy that particles appeared either ""solid"" or ""hollow."" A solid appearance applied to an effective particle density close to the true density of the material, whereas a density around 1 g/cm(3) corresponded to a hollow appearance. However, carbohydrates, which crystallized during spray drying, for example, mannitol appeared solid but the 3 average effective particle density was 0.95 g/cm, indicating a continuous but porous structure. AFM measurements of effective particle density corroborate the suggestion of differences in particle structure caused by the varying propensity of carbohydrates to crystallize during spray drying, resulting in mainly either amorphous hollow or crystalline porous particles.
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8.
  • Elversson, J, et al. (författare)
  • Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying
  • 2003
  • Ingår i: Journal of Pharmaceutical Sciences. - : Wiley. - 0022-3549 .- 1520-6017. ; 92, s. 900-910
  • Tidskriftsartikel (refereegranskat)abstract
    • To find means of controlling the size and density of particles intended for inhalation the relationship between droplet and particle size during spray drying was investigated. Lactose solutions were atomized with a two-fluid nozzle and dried in a laboratory spray drier. The effects of nozzle orifice diameter, atomization airflow and feed concentration on droplet and particle size were examined. Mass median diameter of both droplets and particles were analyzed with laser diffraction. In addition, scanning electron microscopy and transmission electron microscopy were used for studies of particle shape and morphology. It was demonstrated that nozzle orifice diameter and airflow, but not feed concentration controlled the droplet size during atomization. Increasing droplet size increased particle size but the effect was also influenced by feed concentration. Particles from solutions of a low concentration (1% w/w) were smaller than those from higher concentrations (5-20% w/w). This may be partly explained by lower yields at higher feed concentrations, but may also be related to differences in drying rate. Spray-dried lactose solutions formed hollow particles, and it was suggested that the shell thickness of the particles increased with increasing feed concentration
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9.
  • Elversson, Jessica, et al. (författare)
  • Particle size and density in spray drying : effects of carbohydrate properties
  • 2005
  • Ingår i: Journal of Pharmaceutical Sciences. - : Wiley. - 0022-3549 .- 1520-6017. ; 94:9, s. 2049-2060
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to examine some fundamental aspects of the particle formation during spray drying, related to particle size and density. Particles were prepared in a laboratory spray dryer from carbohydrates with different solubility and crystallization propensity, such as lactose, mannitol, and sucrose/dextran 4:1. The feed concentrations ranged from 1% w/w to saturated and the size of droplets and particles were measured by laser diffraction. Particles were also characterized by various microscopy techniques (i.e., scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and light microscopy), differential scanning calorimetry (DSC), gas adsorption, and gas pycnometry. As demonstrated larger particles could be obtained by either increasing the droplet size during atomization; increasing the concentration of the feed solution; or decreasing the solubility of the solute. The apparent particle density, measured by gas pycnometry, was found negatively correlated to the feed concentration. Due to the nonlinear relationship between the feed concentration and the particle size, it was concluded that higher solids load would cause an increase in the effective particle density and that the reduction in the apparent particle density was a result of a gradually less permeable particle surface. Further, the crystallization propensity of the carbohydrate influenced the particle formation and resulted in either hollow or porous particles.
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10.
  • Elversson, J, et al. (författare)
  • Particle size and density in spray drying - effects of carbohydrate properties
  • 2005
  • Ingår i: Journal of Pharmaceutical Sciences. - 0022-3549 .- 1520-6017. ; 94, s. 2049-2060
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to examine some fundamental aspects of the particle formation during spray drying, related to particle size and density. Particles were prepared in a laboratory spray dryer from carbohydrates with different solubility and crystallization propensity, such as lactose, mannitol and sucrose/dextran 4:1. The feed concentrations ranged from 1% w/w to saturated and the size of droplets and particles were measured by laser diffraction. Particles were also characterized by various microscopy techniques (i.e. scanning electron microscopy, confocal laser scanning microscopy and light microscopy), differential scanning calorimetry, gas adsorption, and gas pycnometry. As demonstrated larger particles could be obtained by either increasing the droplet size during atomization; increasing the concentration of the feed solution; or decreasing the solubility of the solute. The apparent particle density was found negatively correlated to the feed concentration. Due to the non-linear relationship between the feed concentration and the particle size, it was concluded that higher solids load may cause an increase in the effective particle density and that the reduction in the apparent particle density was a result of a gradually less permeable particle surface. Further, the crystallization propensity of the carbohydrate influenced the particle formation and resulted in either hollow or porous particles
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