| 1. |
- Brohede, Ulrika, et al.
(författare)
-
A novel graded bioactive high adhesion implant coating
- 2009
-
Ingår i: Applied Surface Science. - : Elsevier BV. - 0169-4332 .- 1873-5584. ; 255:17, s. 7723-7728
-
Tidskriftsartikel (refereegranskat)abstract
- One method to increase the clinical success rate of metal implants is to increase their bone bonding properties, i.e. to develop a bone bioactive surface leading to reduced risks of interfacial problems. Much research has been devoted to modifying the surface of metals to make them become bioactive. Many of the proposed methods include depositing a coating on the implant. However, there is a risk of coating failure due to low substrate adhesion. This paper describes a method to obtain bioactivity combined with a high coating adhesion via a gradient structure of the coating. Gradient coatings were deposited on Ti (grade 5) using reactive magnetron sputtering with increasing oxygen content. To increase the grain size in the coating, all coatings were post annealed at 385 degrees C. The obtained coating exhibited a gradual transition over 70 nm from crystalline titanium oxide (anatase) at the surface to metallic Ti in the substrate, as shown using cross-section transmission electron microscopy and X-ray photoelectron spectroscopy depth pro. ling. Using scratch testing, it could be shown that the adhesion to the substrate was well above 1 GPa. The bioactivity of the coating was verified in vitro by the spontaneous formation of hydroxylapatite upon storage in phosphate buffer solution at 37 degrees C for one week. The described process can be applied to implants irrespective of bulk metal in the base and should introduce the possibility to create safer permanent implants like reconstructive devices, dental, or spinal implants.
|
|
| 2. |
|
|
| 3. |
- 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.
|
|
| 4. |
- Brohede, Ulrika, 1969-
(författare)
-
Drug Diffusion and Nano Excipient Formation Studied by Electrodynamic Methods
- 2007
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- New smart drugs demand new smart drug delivery systems and also new smart analysis methods for the drug delivery process and material characterization. This thesis contributes to the field by introducing a new electrodynamic approach for studying the drug diffusion proc-esses as well as the formation of a new type of drug delivery systems, the so called mesoporous nano excipients.Drug diffusion processes from different pharmaceutical materials were examined. The transport of charged drug substances was investigated by electrodynamic methods; either as a release process governed by diffusion using the alternating ionic current method or by applying a voltage, sinusoidal or dc, to force the drug ions to move in an electric field.Temperature-dependent drug release from microcrystalline cellulose tablets was examined in order to extract information about the diffu-sion process. Percolation theory was also employed to binary mixtures of an insoluble and electrically insulating matrix material together with a soluble and ionic conducting drug. Further, dielectric spectros-copy was proven to be a powerful method for examining the state of vesicle formation of drug and surfactant molecules in a carbopol gel. Finally, a new potential class of pharmaceutical materials were exam-ined, namely the AMS-n mesoporous materials, showing that the al-ternating ionic current method is powerful both in the study of the synthesis of and in the release process from these.
|
|
| 5. |
- Brohede, Ulrika, et al.
(författare)
-
Electrodynamic Investigations of Ion Transport and Structural Properties in Drug-Containing Gels : Dielectric Spectroscopy and Transient Current Measurements on Catanionic Carbopol Systems
- 2005
-
Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 109:32, s. 15250-15255
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study is to show the potential of using electrodynamic methods as characterization tools in the controlled drug release process, on complex drug release systems. The two formulations under study were a Carbopol gel containing diphenhydramine and an identical gel also containing the surfactant sodium dodecyl sulfate which forms catanionic vesicles with the diphenhydramine. The average diffusion coefficients were calculated from both the dielectric spectroscopy and the transient current measurements. Comparing the herein-obtained diffusion coefficients with those obtained in another study using a traditional USP technique for the same system, the values are virtually the same. The two electrodynamic methods proved to be potentially valuable tools for obtaining information about the concentration and the motion of the drug molecules inside the gel. The transient current measurements are particularly interesting in this case, as the method gives information not only on an average level, but also of the different charged moieties separately. Interestingly, it seems that the methods also are applicable for obtaining information about the mesh size in the gel.
|
|
| 6. |
- Brohede, Ulrika, et al.
(författare)
-
Multifunctional implant coatings providing possibilities for fast antibiotics loading with subsequent slow release
- 2009
-
Ingår i: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 20:9, s. 1859-1867
-
Tidskriftsartikel (refereegranskat)abstract
- The possibility to fast-load biomimetic hydroxyapatite coatings on surgical implant with the antibiotics Amoxicillin, Gentamicin sulfate, Tobramycin and Cephalothin has been investigated in order to develop a multifunctional implant device offering sustained local anti-bacterial treatment and giving the surgeon the possibility to choose which antibiotics to incorporate in the implant at the site of surgery. Physical vapor deposition was used to coat titanium surfaces with an adhesion enhancing gradient layer of titanium oxide having an amorphous oxygen poor composition at the interface and a crystalline bioactive anatase TiO2 composition at the surface. Hydroxyapatite (HA) was biomimetically grown on the bioactive TiO2 to serve as a combined bone in-growth promoter and drug delivery vehicle. The coating was characterized using scanning and transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. The antibiotics were loaded into the HA coatings via soaking and the subsequent release and antibacterial effect were analyzed using UV spectroscopy and examination of inhibition zones in a Staphylococcus aureus containing agar. It was found that a short drug loading time of 15 min ensured antibacterial effects after 24 h for all antibiotics under study. It was further found that the release processes of Cephalothin and Amoxicillin consisted of an initial rapid drug release that varied unpredictably in amount followed by a reproducible and sustained release process with a release rate independent of the drug loading times under study. Thus, implants that have been fast-loaded with drugs could be stored for ~10 min in a simulated body fluid after loading to ensure reproducibility in the subsequent release process. Calculated release rates and measurements of drug amounts remaining in the samples after 22 h of release indicated that a therapeutically relevant dose could be achieved close to the implant surface for about 2 days. Concluding, the present study provides an outline for the development of a fast-loading slow-release surgical implant kit where the implant and the drug are separated when delivered to the surgeon, thus constituting a flexible solution for the surgeon by offering the choice of quick addition of antibiotics to the implant coating based on the patient need.
|
|
| 7. |
- Brohede, Ulrika, et al.
(författare)
-
Percolating ion transport in binary mixtures with high dielectric loss
- 2006
-
Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 88
-
Tidskriftsartikel (refereegranskat)abstract
- We investigate the ion transportpercolationproperties of a binary system of an ion conductor (NaCl) and an insulator (ethyl cellulose) for which the ac component of the conductivity is non-negligible over the entire measured frequency range. We find that the dc conductivity, extracted from a well-defined range of frequencies, can be described by a low percolation threshold, ϕc=0.06 three-dimensional conducting network. The low ϕc was explained by the water-layer-assisted ion conduction in micrometer-sized ethyl cellulose channels between NaCl grains. The present findings provide valuable knowledge for the analysis and design of a broad class of ion conducting functional materials.
|
|
| 8. |
|
|
| 9. |
- Brohede, Ulrika, et al.
(författare)
-
Percolation phenomena in controlled drug release matrices studied by dielectric spectroscopy and the alternating ionic current method
- 2007
-
Ingår i: Journal of Non-Crystalline Solids. - : Elsevier BV. - 0022-3093 .- 1873-4812. ; 353:47-51, s. 4506-4514
-
Tidskriftsartikel (refereegranskat)abstract
- The combined radial and axial ionic drug release from – as well as the percolating ionic conductivity in – cylindrical tablets was investigated by the alternating ionic current (AIC) method and dielectric spectroscopy (DS), respectively. The binary tablets consisted of mixtures of insulating ethyl cellulose and the poor ionic conductor model drug NaCl at nine different concentrations. We found that the dc conductivity, extracted from DS in a well-defined range of frequencies by a power-law method, could be described by a NaCl volume fraction percolation threshold of 0.06 in a 3D conducting network. The low threshold was explained by water-layer-assisted ion conduction in μm-sized ethyl cellulose channels between NaCl grains as probed by Hg porosimetry and SEM. The drug release process, as probed by AIC, could be described by a matrix porosity percolation threshold of 0.22, equivalent to a NaCl volume fraction of 0.13. The higher percolation threshold found in the drug release experiments as compared to the DS recordings could be explained by the different probing mechanisms of the analysis methods. The present study should provide valuable knowledge for the analysis of a broad class of ion conducting systems for which the frequency response of the dc ion conductivity is superimposed on other dielectric processes in the dielectric spectrum. It also brings forward knowledge important for the development of controlled drug-delivery vehicles as the presented findings show that the 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.
|
|
| 10. |
- 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.
|
|
