1.
Espefält Westin, Ulrika, et al.
(författare)
Direct nose-to-brain transfer of morphine after nasal administration to rats
2006
Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 23:3, s. 565-572
Tidskriftsartikel (refereegranskat) abstract
PURPOSE: The aim of this study was to quantify the olfactory transfer of morphine to the brain hemispheres by comparing brain tissue and plasma morphine levels after nasal administration with those after intravenous administration. METHODS: Morphine (1.0 mg/kg body weight) was administered via the right nostril or intravenously as a 15-min constant-rate infusion to male rats. The content of morphine and its metabolite morphine-3-glucuronide in samples of the olfactory bulbs, brain hemispheres, and plasma was assessed using high-performance liquid chromatography, and the areas under the concentration-time curves (AUC) were calculated. RESULTS: At both 5 and 15 min after administration, brain hemisphere morphine concentrations after nasal administration were similar to those after i.v. administration of the same dose, despite lower plasma concentrations after nasal administration. The brain hemispheres/plasma morphine AUC ratios for the 0-5 min period were thus approximately 3 and 0.1 after nasal and i.v. administration, respectively, demonstrating a statistically significant early distribution advantage of morphine to the brain hemispheres via the nasal route. CONCLUSION: Morphine is transferred via olfactory pathways to the brain hemispheres, and drug transfer via this route significantly contributes to the early high brain concentrations after nasal administration to rats.
2.
Nilsson, Martin, et al.
(författare)
Conductivity percolation in loosely compacted microcrystalline cellulose : An in situ study by dielectric spectroscopy during densification
2006
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 110:41, s. 20502-20506
Tidskriftsartikel (refereegranskat) abstract
The present study aims at contributing to a complete understanding of the water-induced ionic charge transport in cellulose. The behavior of this transport in loosely compacted microcrystalline cellulose (MCC) powder was investigated as a function of density utilizing a new type of measurement setup, allowing for dielectric spectroscopy measurement in situ during compaction. The ionic conductivity in MCC was found to increase with increasing density until a leveling-out was observed for densities above similar to 0.7 g/cm(3). Further, it was shown that the ionic conductivity vs density followed a percolation type behavior signifying the percolation of conductive paths in a 3D conducting network. The density percolation threshold was found to be between similar to 0.2 and 0.4 g/cm(3), depending strongly on the cellulose moisture content. The observed percolation behavior was attributed to the forming of interparticulate bonds in the MCC and the percolation threshold dependence on moisture was linked to the moisture dependence of particle rearrangement and plastic deformation in MCC during compaction. The obtained results add to the understanding of the density-dependent water-induced ionic transport in cellulose showing that, at given moisture content, the two major parameters determining the magnitude of the conductivity are the connectedness of the interparticluate bonds and the connectedness of pores with a diameter in the 5-20 nm size range. At densities between similar to 0.7 and 1.2 g/cm(3) both the bond and the pore networks have percolated, facilitating charge transport through the MCC compact.
