| 1. |
- Hammarlund-Udenaes, Margareta, et al.
(författare)
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Drug equilibration across the blood-brain barrier : pharmacokinetic considerations based on the microdialysis method
- 1997
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Ingår i: Pharmaceutical research. - 0724-8741 .- 1573-904X. ; 14:2, s. 128-134
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The purpose of the study was to investigate the influence of different rates of transport into and out of the brain, including passive and active transport, on unbound brain concentrations and profile in relation to the blood concentration profile. Special emphasis is put on hydrophilic drugs. METHODS: Simulations were performed with a model including one body compartment and one brain compartment, with linear or saturable transport into and out of the brain. Comparisons were made with experimental results from microdialysis (MD) studies. RESULTS: Three features were evident when combining the MD results: 1) equilibration across the blood-brain barrier (BBB) is rapid, 2) half-life is similar in brain and blood for most drugs, and 3) unbound brain concentrations seldom reach the level of unbound blood concentrations. A low concentration ratio brain:blood is not mainly caused by a low influx, but rather by different influx and efflux clearances. Active transport out of the brain can explain the results, but also active transport into the brain under certain conditions. A small volume of distribution in brain vs. that in the rest of the body contributes to a rapid equilibration and similar half-lives. CONCLUSIONS: Assumptions of slow equilibration of hydrophilic drugs and similar unbound concentrations across the BBB at steady state are contradicted. The results are more in line with recent findings on the presence of P-glycoprotein and other transport mechanisms at the BBB. Non-passive transport across the BBB seems to be the case for almost all drugs studies with MD so far.
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| 2. |
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| 3. |
- Lennernäs, H, et al.
(författare)
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Regional rectal perfusion : a new in vivo approach to study rectal drug absorption in man.
- 1995
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Ingår i: Pharmaceutical research. - 0724-8741 .- 1573-904X. ; 12:3, s. 426-32
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In vivo permeability measurements of drugs in the colonic/rectal region in humans are difficult. A new instrument for the perfusion of a defined and closed segment in the colon/rectum was developed. The objective of this study was to evaluate its use for studying drug absorption mechanisms in the human rectum and to investigate the effect of transmucosal water absorption on drug permeability. Six healthy subjects participated at 2 separate occasions by using a modified system for segmental rectal perfusion. The system consisted of a multichannel tube with inflatable balloons and was endoscopically introduced into the rectum. The technique was considered acceptable by the following criteria; (a) high and reproducible recovery of PEG 4000, (b) stable residence time of the solution within the test segment, (c) flux of electrolytes that agrees with previous reports, (d) mass-balance absorption of antipyrine across the rectal barrier, (e) and good acceptability to the subjects. The permeability of antipyrine in the rectal region was increased by inducing net water absorption. D-glucose was not absorbed during any study periods. The present technique is valuable for studying drug absorption from the human rectum.
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| 4. |
- Sjöström, B, et al.
(författare)
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Structures of nanoparticles prepared from oil-in-water emulsions
- 1995
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Ingår i: Pharmaceutical research. - 0724-8741 .- 1573-904X. ; 12, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Nanometric particles of three mixtures of hydrophobic substances, cholesteryl esters, have been prepared by emulsification in water. These substances were dissolved in an organic solvent which was emulsified with an aqueous solution at very high shear. Droplets of very small sizes (50-100 nm) were obtained using surfactants which were combinations of lecithins and bile salts. After the emulsification was completed, the organic solvent was removed by evaporation, yielding stable suspensions of solid particles. The sizes of these particles did not follow the reduction expected from the removal of organic solvent, indicating that the particles were not dense spheres. According to cryo-transmission electron microscopy and to small angle neutron scattering (SANS) the newly prepared particles are non-aggregated. Furthermore, the results suggest that the emulsifier used in the preparation of the emulsion and the particle core composition determines the morphology of the obtained particles. a) The shape of choleateryl acetate particles stabilized by lecithin and sodium glycocholate was examined by cryo-transmission electron microscopy; and it was found that the particles were platelets with a thickness of 10-20 nm and a diameter of 100 nm. The structures of the particles were also examined by small angle neutron scattering; these results were consistent with a platelet structure. Upon storage at high concentration in water, some aggregation was observed, but the particles remained individual platelets. b) Cholesteryl acetate particles prepared with a sorbitan ester were, on the other hand, spherical according to cryo-transmission electron microscopy and SANS measurements. c) Samples prepared with lecithin as emulsifier and a lipid mixture in the core were
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| 5. |
- Alden, M, et al.
(författare)
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Effect of temperature history on the freeze-thawing process and activity of LDH formulations
- 1997
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Ingår i: PHARMACEUTICAL RESEARCH. - : PLENUM PUBL CORP. - 0724-8741. ; 14:4, s. 426-430
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose. The purpose of the study was to investigate the effect of freeze-thawing processes with different temperature histories on thermal transformations and on protein activity of lactate dehydrogenase (LDH) formulations. Polyethylene glycol (PEG 6000)
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| 6. |
- Anger, S, et al.
(författare)
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High resolution size determination of 20 nm colloidal gold particles by SedFFF
- 1999
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Ingår i: PHARMACEUTICAL RESEARCH. - : KLUWER ACADEMIC/PLENUM PUBL. - 0724-8741. ; 16:11, s. 1743-1747
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose. Assessment of lower size limit of Sedimentation Field-Flow Fractionation (SedFFF), specifically to evaluate if the method is suitable to determine the size and size distribution of 20 nm colloidal gold particles with high resolution. Methods. Sed
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| 7. |
- Sjoberg, H, et al.
(författare)
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A new method for diffusion measurement in polymeric films based on a stacked sheet concept
- 1996
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Ingår i: PHARMACEUTICAL RESEARCH. - : PLENUM PUBL CORP. - 0724-8741. ; 13:12, s. 1871-1874
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Purpose. To develop and evaluate a simple, yet well defined, method to measure diffusion in semi-solids, i.e. polymeric materials. Method The method was based on a concept where equivalent discs of polymeric films were cut and stacked on top of each other
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