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  • 1.
    Adane, M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gebre-Mariam, T
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    The use of extragranular disintegrants in multiple-unit tablet formulations: effect on compressibility, compactibility and disintegration2007In: Journal of drug delivery science and technology, ISSN 1773-2247, Vol. 17, no 4, p. 279-284Article in journal (Refereed)
    Abstract [en]

    Multiple-unit tablets formed from mixtures of microcrystalline cellulose pellets and disintegrants (Ac-Di-Sol, Primojel or Kollidon CL) by compaction were investigated with the aim of controlling tablet tensile strength and disintegration time. The effects of pellet porosity, compaction pressure, and type and amount of disintegrant were studied. Primojel made the pellets less prone to deformation during compression, while the other two disintegrants had very minor effects on the compression behavior. Ac-Di-Sol and Primojel generally increased the tablet tensile strength, whereas the effect of Kollidon CL was dependent on the initial pellet porosity. Kollidon CL was found to significantly reduce the disintegration time, but the other two disintegrants had variable efficacy, and for the low-porosity pellets significantly increased the disintegration time. These results are interpreted as resulting from the interplay between the mechanical characteristics of the pellets and the mechanisms of action of the disintegrants.

  • 2.
    Berggren, Jonas
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Compression behaviour and tablet-forming ability of spray-dried amorphous composite particles.2004In: Eur J Pharm Sci, ISSN 0928-0987, Vol. 22, no 2-3, p. 191-200Article in journal (Other scientific)
  • 3.
    Bramer, Tobias
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gråsjö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Edsman, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Implications of regular solution theory on the release mechanism of catanionic mixtures from gels2009In: Colloids and Surfaces B: Biointerfaces, ISSN 0927-7765, E-ISSN 1873-4367, Vol. 71, no 2, p. 214-225Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to apply the regular solution theory of mixed  micelles to gain new insights on the drug release mechanism, when using   catanionic mixtures as a method of obtaining prolonged release from   gels. Synergistic effects were investigated at equilibrium and   quantified in terms of regular solution theory interaction parameters.  The drug release from catanionic aggregates was studied both in a polymer free environment, using dialysis membranes, and in gels, using  a modified LISP paddle method. The drug release kinetics was modelled   theoretically by combining the regular solution theory with Fick's   diffusion laws assuming a contribution to the transport only from monomeric species (stationary aggregates). The theoretical predictions were found to be in reasonably good agreement with experiments. An analysis of the calculated distribution of species between aggregated and monomeric states was shown to provide further insights into the release mechanism.

  • 4.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Characterization of the drug release process by investigation of its temperature dependence2004In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 93, no 7, p. 1796-1803Article in journal (Refereed)
    Abstract [en]

    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.

  • 5.
    Brohede, Ulrika
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Valizadeh, Sima
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Percolative drug diffusion from cylindrical matrix systems with unsealed boundaries2007In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 96, no 11, p. 3087-3099Article in journal (Refereed)
    Abstract [en]

    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.

  • 6.
    Fichtner, Frauke
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Drug release from compacted single inert matrix agglomerates2007In: Journal of Drug Delivery Science and Technology, ISSN 1773-2247, Vol. 17, no 4, p. 273-277Article in journal (Refereed)
    Abstract [en]

    The effect of compaction on the drug release from single, sodium chloride loaded, microcrystalline cellulose agglomerates of different porosities was investigated in this study. The drug release from uncompacted agglomerates and from agglomerates regained from tablets compacted at a range of different compaction pressures was monitored measuring the conductivity of the dissolution medium in a recirculation flow-through system. The drug release profiles were described using the mean dissolution time (MDT), the variation of dissolution time (VDT) and the relative dispersion coefficient (RD). It was found that depending on physical structure changes of the matrix, the drug release rate of compacted agglomerates could be enhanced or retarded in comparison with uncompacted agglomerates. The retardation is suggested to be due to a densification of the matrix and the enhancement due to a crack formation in the external surface of the matrix.

  • 7.
    Frenning, Goran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Towards a mechanistic contact model for elastoplastic particles at high relative densities2015In: Finite elements in analysis and design (Print), ISSN 0168-874X, E-ISSN 1872-6925, Vol. 104, p. 56-60Article in journal (Refereed)
    Abstract [en]

    Triaxial compression of elastoplastic particles was studied with numerical and analytical methods in order to develop a mechanistic model for their interactions at high relative densities. The introduction of an equivalent particle radius that accounted for the elastic volumetric deformation enabled an almost perfect reduction of the results obtained for elastoplastic particles to those obtained for rigid, perfectly plastic ones. This, in turn, made possible a simplified yet mechanistic analytical analysis of the particle response in terms of the contact area, pressure and force. The developed model exhibited a good agreement with the numerical results, especially for intermediate and large strains, and hence laid the foundations for the development of mechanistic contact models suitable for simulations of granular materials at high relative densities with the Discrete Element Method (DEM).

  • 8.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    An efficient finite/discrete element procedure for simulating compression of 3D particle assemblies2008In: Computer methods in applied mechanics and engineering, ISSN 0045-7825, Vol. 197, no 49/50, p. 4266-4272Article in journal (Refereed)
    Abstract [en]

    An efficient combined finite/discrete element procedure is developed, which is intended for simulating compression of 3D particle assemblies. Its main ingredients are an explicit solution scheme of the predictor–corrector type, an efficient two-stage contact detection algorithm, and physically stabilized elements that require only one integration point. The algorithm admits a straightforward parallelization, with a reasonable parallel efficiency. Our results indicate that realistic systems comprising 1000 or more particles may successfully be analyzed within a reasonable computation time (not more than about 10–15 h).However, the explicit solution scheme limits the applicability of the algorithm in its present form to systems of fairly soft particles, unless special procedures such as mass scaling are used to increase the critical time step.

  • 9.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Analysis of pharmaceutical powder compaction using multiplicative hyperelasto-plastic theory2007In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 172, no 2, p. 103-112Article in journal (Refereed)
    Abstract [en]

    Single-ended compaction of lactose powder is investigated numerically within the framework of multiplicative hyperelasto-plastic theory. In keeping with previous work in the pharmaceutical field, a slightly modified Drucker–Prager Cap model is described and used in the simulations. Coulomb friction is included on all interfaces. Our results indicate that simulations of this type may be useful not only to determine density and stress distributions within tablets, as has been done hitherto, but also may provide indications of circumstances under which the tableting operation fails due to capping.

  • 10.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Compression mechanics of granule beds: A combined finite/discrete element study2010In: Chemical Engineering Science, ISSN 0009-2509, E-ISSN 1873-4405, Vol. 65, no 8, p. 2464-2471Article in journal (Refereed)
    Abstract [en]

    Compression of three-dimensional beds comprising 1000 plastically deforming initially spherical granules is investigated by using the combined finite/discrete element (FE/DE) method. The material model is formulated within the framework of multiplicative plasticity, and utilizes a density-dependent elliptic yield surface that allows porous particles to both deform and to densify plastically, whereas only volume-preserving plastic deformation is possible for nonporous ones. Granules with different characteristics (yield stress and initial porosity) are studied, and the relationship between the single-granule properties and the global compression behaviour of the granule bed is investigated. It is demonstrated that the FE/DE method may shed light on the deformation and densification behaviour of individual granules, since the size and shape of each granule are continually determined as an integral part of the solution procedure, and that the method thus provides a comprehensive picture of the processes occurring during confined compression of granular materials. (C) 2010 Elsevier Ltd. All rights reserved.

  • 11.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Efficient Voronoi volume estimation for DEM simulations of granular materials under confined conditions2015In: MethodsX, ISSN 1258-780X, E-ISSN 2215-0161, Vol. 2, p. 79-90Article in journal (Refereed)
    Abstract [en]

    When the discrete element method (DEM) is used to simulate confined compression of granular materials, the need arises to estimate the void space surrounding each particle with Voronoi polyhedra. This entails recurring Voronoi tessellation with small changes in the geometry, resulting in a considerable computational overhead. To overcome this limitation, we propose a method with the following features: A local determination of the polyhedron volume is used, which considerably simplifies implementation of the method. A linear approximation of the polyhedron volume is utilised, with intermittent exact volume calculations when needed. The method allows highly accurate volume estimates to be obtained at a considerably reduced computational cost.

  • 12.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Modelling drug release from inert matrix systems: From moving-boundary to continuous-field descriptions2011In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 418, no 1, p. 88-99Article, review/survey (Refereed)
    Abstract [en]

    The purpose of this review is to provide a comprehensive overview of mathematical procedures that can be used to describe the release of drugs from inert matrix systems. The review focuses on general principles rather than particular applications. The inherent multiscale nature of the drug-release process is pointed out and multiscale modelling is exemplified for inert porous matrices. Although effects of stagnant layers and finite volumes of release media are briefly discussed, the systematic analysis is restricted to systems under sink conditions. When the initial drug loading exceeds the drug solubility in the matrix, Higuchi-type moving-boundary descriptions continue to be highly valuable for obtaining approximate analytical solutions, especially when coupled with integral balance methods. Continuous-field descriptions have decisive advantages when numerical solutions are sought. This is because the mathematical formulation reduces to a diffusion equation with a nonlinear source term, valid over the entire matrix domain. Solutions can thus be effortlessly determined for arbitrary geometries using standard numerical packages.

  • 13.
    Frenning, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Theoretical analysis of the release of slowly dissolving drugs from spherical matrix systems.2004In: J Control Release, ISSN 0168-3659, Vol. 95, no 1, p. 109-17Article in journal (Other scientific)
  • 14.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Towards a mechanistic model for the interaction between plastically deforming particles under confined conditions: A numerical and analytical analysis2013In: Materials letters (General ed.), ISSN 0167-577X, E-ISSN 1873-4979, Vol. 92, p. 365-368Article in journal (Refereed)
    Abstract [en]

    Triaxial compression of plastically deforming particles was studied with the finite element method in order to identify the mechanisms that underlie the particle response under confined conditions. In addition to the established elastoplastic behaviour at small and intermediate strains, the coalescence of plastic zones centred at contacts resulted in a reduced stiffness, whereas a significantly increased stiffness was seen once the material displaced by plastic deformation filled the ambient void space, signifying the onset of a stage dominated by elastic volume reduction. Moreover, an analytical model for multiple simultaneous contacts was formulated, assuming that the deformed particle shape could be approximated by a truncated sphere and that the behaviour of each individual contact could be described in terms of a hardness. The thus obtained model exhibited a promising agreement with the numerical results.

  • 15.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Ahnfelt, Emelie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Sjögren, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Computational fluid dynamics (CFD) studies of a miniaturized dissolution system2017In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 521, no 1-2, p. 274-281Article in journal (Refereed)
    Abstract [en]

    Dissolution testing is an important tool that has applications ranging from fundamental studies of drugrelease mechanisms to quality control of the final product. The rate of release of the drug from the delivery system is known to be affected by hydrodynamics. In this study we used computational fluid dynamics to simulate and investigate the hydrodynamics in a novel miniaturized dissolution method for parenteral formulations. The dissolution method is based on a rotating disc system and uses a rotating sample reservoir which is separated from the remaining dissolution medium by a nylon screen. Sample reservoirs of two sizes were investigated (SR6 and SR8) and the hydrodynamic studies were performed at rotation rates of 100, 200 and 400 rpm. The overall fluid flow was similar for all investigated cases, with a lateral upward spiraling motion and central downward motion in the form of a vortex to and through the screen. The simulations indicated that the exchange of dissolution medium between the sample reservoir and the remaining release medium was rapid for typical screens, for which almost complete mixing would be expected to occur within less than one minute at 400 rpm. The local hydrodynamic conditions in the sample reservoirs depended on their size; SR8 appeared to be relatively more affected than SR6 by the resistance to liquid flow resulting from the screen.

  • 16.
    Frenning, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Evolution of distributions and spatial correlations of single-particle forces and stresses during compression of ductile granular materials.2005In: Phys Rev E Stat Nonlin Soft Matter Phys, ISSN 1539-3755, Vol. 71, no 1 Pt 1, p. 011305-Article in journal (Refereed)
  • 17.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Kish, Laszlo B.
    Mahlin, Denny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Spectral analysis of force fluctuations during probe penetration into cohesive powders2008In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 187, no 1, p. 62-67Article in journal (Refereed)
    Abstract [en]

    We investigate force fluctuations during probe penetration into cohesive powders consisting of ∼5 μm lactose particles with varying surfaceproperties prepared by spray drying. The results obtained for the more cohesive powders were remarkably similar to those previously reported fororders of magnitude larger noncohesive particles. For the less cohesive powders, the spectral densities were instead found to exhibit two distinctpower-law regions. Furthermore, the spectra were found to be independent of the geometry of the penetrating probe and dimensions of the diecavity. These findings suggest that the response is dominated by particle aggregate or agglomerate movement for the more cohesive powders,whereas the behaviour of the less cohesive ones is consistent with a response dominated by relatively weak force chains, with the fluctuations resulting from the recurring creation and collapse of jammed states being damped for length scales N0.1 mm.

  • 18.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Brohede, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences.
    Finite element analysis of the release of slowly dissolving drugs from cylindrical matrix systems2005In: Journal of Controlled Release, ISSN 0168-3659, E-ISSN 1873-4995, Vol. 107, no 2, p. 320-329Article in journal (Refereed)
    Abstract [en]

    Drug release from matrix systems of cylindrical shape is analyzed in detail by using the finite element method. The model used combines the Noyes-Whitney and diffusion equations, and thus takes the effects of a finite dissolution rate into account. The model is valid for all drug solubilities and dissolution rates, and allows accurate predictions of the drug release to be made. Anisotropic drug transport that may result from the manufacturing process is properly accounted for. Model calculations show that a finite dissolution rate may affect the release profile significantly, producing an initial delay. The equivalence between anisotropic release and isotropic release from a matrix with different dimensions is demonstrated. Comparisons are made with the predictions of a recently proposed pseudo-steady state (PSS) analysis of drug release from cylindrical matrices [Y. Zhou, J. S. Chu, T. Zhou, X. Y. Wu, Modeling of dispersed-drug release from two-dimensional matrix tablets, Biomaterials 26 (2005) 945-952]. This comparison reveals that important discrepancies exist between the numerical and analytical results, which are attributed to the simplifying assumption made in the PSS analysis that the region containing solid drug remains cylindrical in shape throughout the release process. The proposed model is shown to describe experimental release data well.

  • 19.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Ek, Ragnar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    A new method for characterizing the release of drugs from tablets in low liquid surroundings2002In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 91, no 3, p. 776-784Article in journal (Refereed)
    Abstract [en]

    The purpose of this article is to introduce a method capable of determining early drug dissolution in small amounts of liquid. The method is based on the measurement of the alternating ionic current through a cell containing the dissolution medium and the substance to be dissolved. Both the initial and more prolonged absorption of liquid into tablets can also be determined by using the same technique. The method has been tested on two tablet formulations containing agglomerated micronized cellulose and NaCl as a model drug. Release of NaCl was delayed from both formulations; the extent of the delay was strongly formulation-dependent only when the surrounding liquid was in short supply. This finding shows that new drug dissolution phenomena may be encountered in small liquid volumes; these phenomena would not have been seen with the large volume methods normally used in in vitro dissolution tests. Hence, for formulations intended for sublingual, buccal, or rectal administration, i.e., in areas where liquid is scarce, in vitro dissolution tests should be performed in small volumes of dissolution medium.

  • 20.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Engelmark, Fredrik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Niklasson, Gunnar A
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Li conduction in sputtered amorphous Ta2O52001In: Journal of the Electrochemical Society, ISSN 0013-4651, E-ISSN 1945-7111, Vol. 148, no 5, p. A418-A421Article in journal (Refereed)
    Abstract [en]

    Electron and Li ion conducting properties of room temperature sputtered amorphous tantalum oxide (a-Ta2O5) films were studied in order to evaluate the feasibility of using a-Ta2O5 in electrochromic device applications. The films were investigated using the galvanostatic intermittent titration technique, impedance spectroscopy, and isothermal transient ionic current measurements. It was found that the a-Ta2O5 met two out of three requirements posed on a Li ion conductor in a WO3 based electrochromic device. There was a negligible intercalation in the potential window used in WO3-based electrochromic devices (above 2.4-2.5 V vs. Li/Li+). Furthermore, in this potential region, the chemical diffusion coefficient for Li was larger than the corresponding quantity in WO3. However, there was a nonzero electron conductivity in the a-Ta2O5 films, not observed in the chemical vapor deposition-made β-Ta2O5 investigated earlier. Still, the ionic conductivity was approximately one order of magnitude larger than the electronic one.

  • 21.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Fichtner, Frauke
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    A new method for characterizing the release of drugs from single agglomerates2005In: Chemical Engineering Science, ISSN 0009-2509, E-ISSN 1873-4405, Vol. 60, no 14, p. 3909-3918Article in journal (Refereed)
  • 22.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gråsjö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    The Release of Catanionic Mixtures Embedded in Gels: An Approximate Analytical Analysis2011In: AIChE Journal, ISSN 0001-1541, E-ISSN 1547-5905, Vol. 57, no 6, p. 1402-1408Article in journal (Refereed)
    Abstract [en]

    We present an approximate analytical analysis of the release of catanionic mixtures from gels. The starting points are the monomer-mixed micelle equilibrium, described by using regular solution theory, and the one-dimensional diffusion equation. Focusing on a half-infinite planar system, we first point out an exact reduction of the problem to a system of ordinary differential equations. By using the pseudo-steady-state approximation and the integral-balance method, we then derive a single nonlinear equation for the mole fraction of drug in micelles at the extraction front. This equation may be readily solved numerically (or graphically), and once the solution is found, all quantities of interest may be determined in closed form. Comparisons with numerical solutions of the fully nonlinear problem indicate that the errors resulting from the approximations typically do not exceed 10%.

  • 23.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Jonsson, AnnaKarin
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Larsson, A.-L.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Materials Science.
    Theoretical investigation of ion conduction in three-layered ion-conductor systems: Derivation of the isothermal transient ionic current and frequency-dependent impedance2003In: Journal of Applied Physics, ISSN 0021-8979, E-ISSN 1089-7550, Vol. 94, p. 1629-Article in journal (Refereed)
    Abstract [en]

    Ion conduction in three-layered ion-conductor systems is considered. Explicit analytic expressions for the isothermal transient ionic current and frequency-dependent impedance are derived. The analysis includes migration, diffusion and space-charge effects as contributors to the ionic motion. The resulting model allows conduction parameters such as diffusion coefficients and ion concentrations in three different layers to be obtained from one single measurement, either in the time or in the frequency domain. The implications of one or more of the layers being mixed ionic/electronic conductors are discussed, and it is argued that the proposed model provides a useful description of the coupled ionic/electronic motion occurring in such a mixed-conductor system.

  • 24.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Mahmoodi, Foad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nordström, Josefina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    An effective-medium analysis of confined compression of granular materials2009In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 194, no 3, p. 228-232Article in journal (Refereed)
    Abstract [en]

    A simplified model for confined compression of granular materials is considered, which idealizes the collection of particles as a (central) force network. Applying an effective-medium procedure, an equation with micromechanically well-defined parameters is derived, which relates the applied pressure to the engineering strain of the powder during uniaxial compression. Despite the simplicity of the model, comparison with experimental data for mm-sized spherical granules indicates that this equation is able to satisfactorily predict the overall compression profile from single-particle data.

  • 25.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Nilsson, M
    Westlinder, Jörgen
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Niklasson, Gunnar A
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Strømme Mattsson, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Dielectric and Li transport properties of electron conducting and non-conducting sputtered amorphous Ta2O5 films2001In: Electrochimica Acta, ISSN 0013-4686, E-ISSN 1873-3859, Vol. 46, no 13-14, p. 2041-2046Article in journal (Refereed)
    Abstract [en]

    Two types of sputtered thin film amorphous tantalum oxide (Ta2O5) were studied: one electron conducting Ta2O5 (ec-Ta2O5) and the other non-conducting Ta2O5 (nc-Ta2O5). The as-deposited films were characterized by impedance spectroscopy (IS) and isothermal transient ionic current (ITIC) measurements. From IS, the dc conductivity 2×10−14 S/cm was obtained for the ec-Ta2O5 film at an applied ac potential of 50 mV whereas a value ≤1×10−17 S/cm was obtained for the nc-Ta2O5 film. Li conducting properties were studied using the galvanostatic intermittent titration technique and ITIC measurements on the intercalated samples. Despite the very dissimilar dc conductivities of the as-deposited films, the two Ta2O5 samples showed surprisingly similar Li ion conducting properties for small Li/Ta2O5 ratios. The Li ion mobility was in the range 1.1×10−9–3.0×10−9 cm2/V s for both films. However, the Li storage behaviour as well as the chemical diffusion coefficient differed. For the nc-Ta2O5 film a plateau was observed in the equilibrium potential vs. composition curve for Li/Ta2O5 ratios between 7×10−5 and 2×10−3. This plateau was likely to have been caused by attractive interactions between the intercalated ions, possibly large enough to cause phase separation. The attractive interactions were shown to suppress the chemical diffusion coefficient in this composition range.

  • 26.
    Frenning, Göran
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Galenisk farmaci.
    Nilsson, Martin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanoteknologi och funktionella material.
    Strømme, Maria
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Technology, Department of Engineering Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Nanoteknologi och funktionella material.
    A generalized regular singular-point description of low-frequency dielectric responses2004In: Phys. Rev. B, Vol. 70, p. 012506-1Article in journal (Refereed)
  • 27.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nordström, Josefina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Effective Kawakita parameters for binary mixtures2009In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 189, no 2, p. 270-275Article in journal (Refereed)
    Abstract [en]

    Despite the fact that many industrial processes use mixtures of powders   with different physical and mechanical properties, most fundamental   studies of powder compression have focused on single-component systems.   There is thus an obvious need for an improved understanding of the   compression behaviour of mixtures of particulate and granular solids.   In this contribution, we show that the Kawakita equation may be   particularly useful in this regard. The reason for this is that the   degree of compression (i.e., the ratio between the volume reduction and   the initial powder volume) for sufficiently high compression pressures   P is a linear function of I I P. For ideal mixtures, for which the   volume of each component may be determined independently of the others,   this linearity implies that effective Kawakita parameters for the   mixture may be readily expressed in terms of the parameters of its   components. In order to validate the proposed approach, binary mixtures   of mm-sized spherical agglomerates prepared by wet granulation followed   by extrusion and spheronization were investigated experimentally.   Predicted and measured Kawakita parameters were generally in good   agreement, indicating that the assumption of ideal mixing behaviour is   valid for this type of systems.

  • 28.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Theoretical derivation of the isothermal transient ionic current in an ion conductor: Migration, diffusion, and space-charge effects2001In: Journal of Applied Physics, ISSN 0021-8979, E-ISSN 1089-7550, Vol. 90, no 11, p. 5570-5575Article in journal (Refereed)
    Abstract [en]

    The Green’s function technique was used to determine the isothermal transient ionic current (ITIC) caused by the application of a constant potential across an ion conductor which initially contained the ions under consideration. The analysis included migration, diffusion, and space-charge effects as contributions to the ionic motion. Furthermore, the relative importance of diffusion and space-charge effects as currentlimiters was investigated. It was found that ion concentrations as low as ∼1016–1017 cm−3 are sufficient to make space-charge effects the dominant contribution to the decay of the ITIC at low applied electric fields(∼104 V/cm). Hence such effects should be taken into consideration when the ITIC method is used to determine conduction parameters.

  • 29.
    Frenning, Göran
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Drug release modeled by dissolution, diffusion, and immobilization2003In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 250, no 1, p. 137-145Article in journal (Refereed)
    Abstract [en]

    This article presents a novel drug release model that combines drug dissolution, diffusion, and immobilization caused by adsorption of the drug to the tablet constituents. Drug dissolution is described by the well-known Noyes–Whitney equation and drug adsorption by a Langmuir–Freundlich adsorption isotherm, and these two processes are included as source and sink terms in the diffusion equation. The model is applicable to tablets that disintegrate into a number of approximately spherical fragments. In order to simplify the analysis it is assumed that liquid absorption, matrix swelling, and tablet disintegration are much faster than drug dissolution and subsequent drug release. The resulting model is shown to yield release characteristics in good agreement with those observed experimentally.

  • 30.
    Gernandt, Jonas
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Richtering, Walter
    Hansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    A model describing the internal structure of core/shell hydrogels2011In: Soft Matter, ISSN 1744-683X, E-ISSN 1744-6848, Vol. 7, no 21, p. 10327-10338Article in journal (Refereed)
    Abstract [en]

    We apply a theory to the constrained swelling of gel particles, explicitly accounting for the propagation of elastic forces through the particle. This approach, together with conventional thermodynamics of gel swelling, allows modelling of the equilibrium state of gels with properties that are spatially inhomogeneous. In our case we consider both a discrete inhomogeneity in the form of assigning different water solubilities to the core and shell domains of the particle, and a continuous inhomogeneity in allowing the density of chemical cross-links to vary gradually through the network. The model is used to understand the behaviour of temperature-sensitive poly(N-isopropyl acrylamide) core/poly(N-isopropyl methacrylamide) shell microgels investigated in an earlier experimental study. How the swelling of the core and shell is affected by the presence of each other at different temperatures is investigated and explained from a mechanical and thermodynamic perspective.

  • 31.
    Jonsson, AnnaKarin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Nilsson, M
    Strømme Mattsson, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Niklasson, Gunnar A
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Materials Science.
    Dielectric study of thin films of Ta2O5 and ZrO22001In: IEEE transactions on dielectrics and electrical insulation, ISSN 1070-9878, E-ISSN 1558-4135, Vol. 8, no 4, p. 648-651Article in journal (Refereed)
    Abstract [en]

    Electronic conduction in sputtered Ta2O5 and ZrO2 thin films have been studied using impedance spectroscopy, isothermal transient ionic current, and current-voltage measurements. The dielectric properties of Ta2O5 were shown to be sensitively dependent on deposition parameters with two different frequency responses: a flat loss behavior with very low DC conductivity, or a relaxation peak together with a somewhat higher DC conductivity. ZrO2 has different dielectric properties when fresh, i.e. newly deposited, or aged. A fresh sample arbitrarily can show two different behaviors, consisting of a DC conductivity with a relaxation peak superimposed on it. The DC conductivity shows either of two different values. The aged sample has a lower permittivity and DC conductivity, and the relaxation peak is found at much lower frequencies. Fresh samples of ZrO2 also show switching behavior

  • 32.
    Jonsson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Evaluation of bulk compression using a discrete element procedure calibrated with data from triaxial experiments on single particles2019In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 345, p. 74-81Article in journal (Refereed)
    Abstract [en]

    Confined compression of bimodal mixtures of ideal spherical cellulose acetate (CA) particles (diameters 1.5 and 2.0 mm) was studied numerically with the discrete element method (DEM) and experimentally using a materials tester equipped with suitable tablet tooling. An extended truncated sphere contact model was used in the simulations, enabling them to be carried out to high relative densities (approaching and sometimes exceeding unity). In order to calibrate this model, the contact pressure development was extracted from prior experimental investigations on single 2.0-mm large CA particles. Results from the simulations were evaluated with the Kawakita and Heckel compression equations and compared to the corresponding data obtained from bulk compression experiments. Generally, a high degree of similarity between experiments and simulations was observed, showing the usefulness of combining confined single particle compression experiments with a suitable numerical model when predicting the performance of powder compression to high relative densities.

  • 33.
    Jonsson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Investigations of single microcrystalline cellulose-based granules subjected to confined triaxial compression2016In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 289, p. 79-87Article in journal (Refereed)
    Abstract [en]

    Confined triaxial compression of single granules was performed in order to assess the contact force development and modes of granule deformation under these conditions. In the study, four microcrystalline cellulose-based granule types of different characteristics were investigated. Results from triaxial single-granule compression experiments were evaluated using an analytical model as well as by comparison to unconfined single-granule compression and to confined bulk compression experiments. It was observed that single granules deform and densify, but tend to keep their integrity during confined triaxial compression, as evident from both compression data and from morphological analysis. Results from confined single granule compression were well represented by the analytical model. These results also largely reflected those from bulk compression experiments, including features of the force-displacement curves as well as rank order between the granule types in terms of contact stiffness. Furthermore, it was shown that intragranular porosity to a high extent governs the onset of plastic incompressibility.

  • 34.
    Jonsson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gråsjö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Mechanical behaviour of ideal elastic-plastic particles subjected to different triaxial loading conditions2017In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 315, p. 347-355Article in journal (Refereed)
    Abstract [en]

    The contact force development for two types of polymeric elastoplastic particles subjected to different triaxial loading conditions was studied experimentally utilising a unique triaxial testing apparatus. In order to evaluate the experimental results, a finite element analysis was performed. The experimental findings highlighted the importance of contact dependence, which manifested itself in two principally different ways. Firstly, a reduced stiffness was observed when plastic deformation ceased to be fully contained, which, depending on the loading conditions, occurred at an engineering strain of about 5-10%. Secondly, a markedly increased stiffness was observed when particle confinement inhibited further plastic deformation, making elastic volume reduction the predominant deformation mode. The experimental results could be well reproduced by the numerical simulations, provided that isotropic hardening was included in the elastoplastic model. In an attempt to invariantly describe the data, a nominal contact pressure was determined as a function of the volumetric constraint of the particle. This resulted in an adequate collapse of results obtained for different loading conditions onto a single master curve at large volumetric constraint. In summary, this paper should be considered as a step along the pathway towards our long term goal of introducing novel and improved contact models.

  • 35.
    Jonsson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gråsjö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nordström, Josefina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Johansson, Niklas
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    An apparatus for confined triaxial testing of single particles2015In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 270, p. 121-127Article in journal (Refereed)
    Abstract [en]

    A novel triaxial apparatus employing overlapping rigid boundaries has been designed and constructed for experimental measurement of contact forces under confined compression of single granules in the mm-scale. The performance of the apparatus was evaluated by performing uniaxial and triaxial compression experiments on ideal elastic-plastic materials. Compression curves were compared with the fully plastic Abbott-Firestone contact model and with results from FEM simulations. The increase in contact force associated with confined conditions was observed in the compression curves from triaxial compression experiments, as supported by predictions from simulations using single particle contact models. Hence, a new method for the assessment of mechanical behaviour of single particles under confined compression can be considered as established.

  • 36.
    Jonsson, Henrik
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Öhman-Mägi, Caroline
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Isaksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Crack nucleation and propagation in microcrystalline-cellulose based granules subject to uniaxial and triaxial load2019In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 559, p. 130-137Article in journal (Refereed)
    Abstract [en]

    Cracking patterns in four kinds of granules, based on the common pharmaceutical excipient microcrystalline cellulose (MCC) and subject to compressive load, were examined. The initial pore structure and the location of initial failure under uniaxial compression were assessed using X-ray micro-computed tomography, whereas contact force development and onset of cracking under more complex compressive load were examined using a triaxial testing apparatus. Smoothed particle hydrodynamics (SPH) simulations were employed for numerical analysis of the stress distributions prior to cracking. For granules subject to uniaxial compression, initial cracking always occurred along the meridian and the precise location of the crack depended on the pore structure. Likewise, for granules subject to triaxial compression, the fracture plane of the primary crack was generally parallel to the dominant loading direction. The occurrence of cracking was highly dependent on the triaxiality ratio, i.e. the ratio between the punch displacements in the secondary and dominant loading directions. Compressive stresses in the lateral directions, induced by triaxial compression, prevented crack opening and fragmentation of the granule, something that could be verified by simulations. These results provide corroboration as well as further insights into previously observed differences between confined and unconfined compression of granular media.

  • 37.
    Jämstorp, Erik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strømme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Modeling structure-function relationships for diffusive drug transport in inert porous geopolymer matrices2011In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 100, no 10, p. 4338-4348Article in journal (Refereed)
    Abstract [en]

    A unique structure-function relationship investigation of mechanically strong geopolymer drug delivery vehicles for sustained release of potent substances is presented. The effect of in-synthesis water content on geopolymer pore structure and diffusive drug transport is investigated. Scanning electron microscopy, N(2) gas adsorption, mercury intrusion porosimetry, compression strength test, drug permeation, and release experiments are performed. Effective diffusion coefficients are measured and compared with corresponding theoretical values as derived from pore size distribution and connectivity via pore-network modeling. By solely varying the in-synthesis water content, mesoporous and mechanically strong geopolymers with porosities of 8%-45% are obtained. Effective diffusion coefficients of the model drugs Saccharin and Zolpidem are observed to span two orders of magnitude (∼1.6-120 × 10(-8) cm(2) /s), comparing very well to theoretical estimations. The ability to predict drug permeation and release from geopolymers, and materials alike, allows future formulations to be tailored on a structural and chemical level for specific applications such as controlled drug delivery of highly potent substances.

  • 38.
    Mahlin, D
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Unga, J
    Ridell, A
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Engström, S
    Influence of polymer molecular weight on the solid-state structure of PEG/Monoolein mixtures2005In: Polymer, Vol. 46, no 26, p. 12210-Article in journal (Refereed)
  • 39.
    Mahlin, Denny
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Ridell, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Engström, Sven
    Solid-state characterisation of PEG 4000/monoolein mixtures2004In: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 37, no 7, p. 2665-2667Article in journal (Refereed)
  • 40.
    Mahmoodi, Foad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    An experimental evaluation of an effective medium based compaction equation2012In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 46, no 1-2, p. 49-55Article in journal (Refereed)
    Abstract [en]

    Tablet production involves compression of free flowing powder in an enclosed cavity of defined geometry. The complexity of the powder bed system necessitates that a way be found to better understand what occurs during compression. One such approach is by means of compaction equations, of which, the Heckel and Kawakita equations are the best known. This work attempts to experimentally evaluate the applicability of the effective medium (EM) equation introduced by Frenning et al. (2009) to powder systems. Two powder types (sodium chloride and lactose monohydrate), each consisting of three size fractions (<40, 125-212 and 212-300 mu m) were characterised and compressed to a pressure of 500 MPa. These powders were chosen because of their differing mechanical properties. An invariance which is inherent in the EM equation is exposed by varying the starting points of compression, and can yield insights into compression mechanisms. Such invariant regions were observed once plastic particle deformation started to dominate the compression behaviour, and enabled the determination of the point where particle rearrangement stops.

  • 41.
    Mahmoodi, Foad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Effect of lubrication on the distribution of force between spherical agglomerates during compression2010In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 198, no 1, p. 69-74Article in journal (Refereed)
    Abstract [en]

    We employ the carbon paper technique to aid the understanding of in die force and spatial distributions, upon compression of approximately I mm sized spherical agglomerates (pellets) of microcrystalline cellulose (MCC). The aim in this study was to test for the effect of lubricant film on force and spatial distributions. Pellets of MCC were formed via granulation and extrusion/spheronisation. Investigation of pellet bed compression was performed on a materials tester. Prior to compression studies the pellets were characterised for bulk density. size and deformability. Two pellet types were investigated; MCC and MCC lubricated with magnesium stearate. The carbon paper technique relies upon carbon paper as the medium for transferring imprints from compressed pellets onto photo quality paper. The digitised images of these imprints form the basis of analysis through the use of image processing software. Using the carbon paper technique within the range of 10-30 MPa indicates that lubrication does not have a significant effect on the distribution of forces between spherical agglomerates during uniaxial compression. Spatial analysis of the imprints revealed that the lubricated pellets exhibited a higher packing order than the unlubricated ones at low applied pressures (10 and 20 MPa), a difference that could not be observed at 30 MPa. Hence interparticle friction and/or cohesion appear to influence the initial particle rearrangement, whereas confinement is suggested to dominate at higher pressures.

  • 42.
    Mahmoodi, Foad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Effect of spherical-agglomerate strength on the distribution of force during uniaxial compression2011In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 206, no 3, p. 283-290Article in journal (Refereed)
    Abstract [en]

    We employ the carbon paper technique with the aim of investigating the effect of spherical-agglomerate (pellet) strength on force distributions, through confined compression of approximately 1 mm sized pellets formed from microcrystalline cellulose and polyethylene glycol. The carbon paper technique relies on the transference of imprints from compressed pellets onto white photo quality paper, which are digitised and processed via image processing software. The investigated pellets can both deform plastically and develop localised cracks in response to an applied stress, while remaining largely intact during confined compression. Our results indicate that such crack formation - henceforth referred to as fracture - has a decisive influence on force distributions. Previous work on non-fracturing systems has found that the distribution of normalized forces tends to narrow with increasing particle deformation. No narrowing is observed after the point of fracture in this study and the width of the distributions - as quantified by the standard deviation of non-normalized forces - is found to increase with the difference between non-normalized mean force and fracture force. Additional corroborative results show that spatial force-force correlations typically exhibit a marked change once the fracture force is exceeded.

  • 43.
    Mahmoodi, Foad
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Klevan, Ingvild
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nordström, Josefina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    A comparison between two powder compaction parameters of plasticity: The effective medium A parameter and the Heckel 1/K parameter2013In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 453, no 2, p. 295-299Article in journal (Refereed)
    Abstract [en]

    The purpose of the research was to introduce a procedure to derive a powder compression parameter (EM A) representing particle yield stress using an effective medium equation and to compare the EM A parameter with the Heckel compression parameter (1/K). 16 pharmaceutical powders, including drugs and excipients, were compressed in a materials testing instrument and powder compression profiles were derived using the EM and Heckel equations. The compression profiles thus obtained could be sub-divided into regions among which one region was approximately linear and from this region, the compression parameters EM A and 1/K were calculated. A linear relationship between the EM A parameter and the 1/K parameter was obtained with a strong correlation. The slope of the plot was close to 1 (0.84) and the intercept of the plot was small in comparison to the range of parameter values obtained. The relationship between the theoretical EM A parameter and the 1/K parameter supports the interpretation of the empirical Heckel parameter as being a measure of yield stress. It is concluded that the combination of Heckel and EM equations represents a suitable procedure to derive a value of particle plasticity from powder compression data.

  • 44.
    Mansson, Ronja
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Malmsten, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Factors Affecting Enzymatic Degradation of Microgel-Bound Peptides2013In: Biomacromolecules, ISSN 1525-7797, E-ISSN 1526-4602, Vol. 14, no 7, p. 2317-2325Article in journal (Refereed)
    Abstract [en]

    Proteolytic degradation and release of microgel-bound peptides was investigated for trypsin, poly(acrylic acid-co-acrylamide) microgels (70-90 mu m in diameter), and oppositely charged polylysine, using a method combination of confocal microscopy and micromanipulator-assisted light microscopy. Results show that trypsin-induced release of polylysine increased with increasing trypsin concentration, decreasing microgel charge density and decreasing peptide molecular weight. While the microgel offered good protection against enzymatic degradation at high microgel charge density, it was also observed that the cationic peptide enabled trypsin to bind throughout the peptide-loaded microgels, even when it did not bind to the peptide-void ones. With the exception of highly charged microgels, proteolytic degradation throughout the peptide-loaded microgel resulted in the generation of short and non-adsorbing peptide stretches, giving rise to the concentration and peptide length dependence observed. A simple random scission model was able to qualitatively capture these experimental findings. collectively, the results demonstrate that microgel charge density, peptide molecular weight, and enzyme concentration greatly influence degradation/release of microgel-bound peptides and need to be considered in the use of microgels, e.g., as carriers for protein and peptide drugs.

  • 45.
    Mihranyan, Albert
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Fransén, Nelly
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Order and disorder in powder mixtures: Spatial distribution functions as tools to assess powder homogeneity2009In: Particle & particle systems characterization, ISSN 0934-0866, E-ISSN 1521-4117, Vol. 25, no 5-6, p. 397-405Article in journal (Refereed)
    Abstract [en]

    In interactive mixtures with small carrier particles, the content variability is often higher than predicted by available models despite the significant degree of interaction visualized with Scanning Electron Microscopy (SEM). The present work details how pair-correlation functions can be used to reveal information about the spatial distribution of mixture constituents and their interactions. SEM pictures of a 2 % w/w oxazepam/sodium starch glycolate (SSG) mixture were recorded (n = 14). The constituent coordinates were extracted and pair-correlation functions as well as the cross-correlation function were calculated. A significant degree of interaction was observed between the constituents in the experimental mixture, compared to a randomized control system. In particular, the probability of finding an oxazepam particle was especially high inside the perimeter of the carrier particle and along its edges. The observed cross-correlation between oxazepam and SSG particles was periodic and repeated at distances corresponding to 1-1.5 carrier diameters. It was concluded that interactive mixtures of powders can be compared to disordered/amorphous solids since both exhibit short-range order, whilst lacking long-range translational periodicity.

  • 46.
    Nilsson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Gråsjö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Conductivity percolation in loosely compacted microcrystalline cellulose: An in situ study by dielectric spectroscopy during densification2006In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 110, no 41, p. 20502-20506Article in journal (Refereed)
    Abstract [en]

    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.

  • 47.
    Nordström, Josefina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Compressibility and tablet forming ability of bimodal granule mixtures: Experiments and DEM simulations2018In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 540, no 1-2, p. 120-131Article in journal (Refereed)
    Abstract [en]

    Compressibility and tablet forming ability (compactibility) of bimodal mixtures of differently sized granules formed from microcrystalline cellulose were studied experimentally and numerically with the discrete element method (DEM). Compression data was analysed using the Kawakita equation. A multi-body contact law that accounts for contact dependence resulting from plastic incompressibility/geometric hardening was used in the DEM simulations. The experimental Kawakita a and 1/b parameters both depended non-monotonically on composition (weight fraction of large particles). For the a parameter, this dependence was explained by variations in the porosity of the initial granule beds; for the 1/b parameter, other factors were found to be of importance as well. The numerical results generally compared favourably with the experiments, demonstrating the usefulness of the DEM at high relative densities, provided that a suitable multi-particle contact model is used. For all mixtures, the tensile strength of the formed tablets increased with increasing applied pressure. The tensile strength generally decreased with increasing fraction of large particle, and this decrease was more rapid for large differences in particle size. A possible interpretation of these findings was proposed, in terms of differences in lateral support of small particles in the vicinity of large particles.

  • 48.
    Nordström, Josefina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Persson, Ann-Sofie
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lazorova, Lucia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Goran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    The degree of compression of spherical granular solids controls the evolution of microstructure and bond probability during compaction2013In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 442, no 1-2, p. 3-12Article in journal (Refereed)
    Abstract [en]

    The effect of degree of compression on the evolution of tablet microstructure and bond probability during compression of granular solids has been studied. Microcrystalline cellulose pellets of low (about 11%) and of high (about 32%) porosity were used. Tablets were compacted at 50, 100 and 150 MPa applied pressures and the degree of compression and the tensile strength of the tablets determined. The tablets were subjected to mercury intrusion measurements and from the pore size distributions, a void diameter and the porosities of the voids and the intra-granular pores were calculated. The pore size distributions of the tablets had peaks associated with the voids and the intra-granular pores. The void and intra-granular porosities of the tablets were dependent on the original pellet porosity while the total tablet porosity was independent. The separation distance between pellets was generally lower for tablets formed from high porosity pellets and the void size related linearly to the degree of compression. Tensile strength of tablets was higher for tablets of high porosity pellets and a scaled tablet tensile strength related linearly to the degree of compression above a percolation threshold. In conclusion, the degree of compression controlled the separation distance and the probability of forming bonds between pellets in the tablet. 

  • 49.
    Nordström, Josefina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    On the physical interpretation of the Kawakita and Adams parameters derived from confined compression of granular solids2008In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 182, no 3, p. 424-435Article in journal (Refereed)
    Abstract [en]

    The objective of this paper was to investigate the physical significance of the Kawakita and Adams parameters derived from the compressionof some granular solids. Four model granules of different expected deformation behaviour were prepared by varying the composition and porosityof the granules. The granules were nearly spherical and of similar size and showed a variation in mechanical properties in terms of their elasticity,plasticity, fracture strength and brittleness. Due to the size and shape of the granules, compression due to granule rearrangement was generallylimited. The Kawakita a parameter approximated the maximal engineering strain of the granular solids and both the Kawakita a and b−1parameter reflected the plasticity of the granules. The Adams parameter τ0 seemed to reflect the initial cracking of granules. Thus, the combineduse of the Kawakita parameters a and b−1 and the Adams parameter τ0 may give a comprehensive representation of the compression behaviour ofgranular solids.

  • 50.
    Nordström, Josefina
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Welch, Ken
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Frenning, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alderborn, Göran
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    On the role of granule yield strength for the compactibility of granular solids2008In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 97, no 11, p. 4807-4814Article in journal (Refereed)
    Abstract [en]

    The objective of this article was to explore the relationship between mechanical properties of single granules and the evolution in tensile strength and tablet micro-structure. Granules of different expected deformation behavior were used as model materials. It is suggested that the role of plasticity in this context is twofold: firstly, to affect the rate of compactibility and thus the pressure range needed to reach the maximal attained tablet strength and, secondly, to affect the mode of deformation of the granules and thus the maximal attained tablet strength. A decrease in yield pressure of single granules increased the tablet tensile strength at a given compaction pressure. The yield pressure can be controlled by the granule composition and porosity.

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