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Nordström, Josefina
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Publications (9 of 9) Show all publications
Nordström, J., Alderborn, G. & Frenning, G. (2018). Compressibility and tablet forming ability of bimodal granule mixtures: Experiments and DEM simulations. International Journal of Pharmaceutics, 540(1-2), 120-131
Open this publication in new window or tab >>Compressibility and tablet forming ability of bimodal granule mixtures: Experiments and DEM simulations
2018 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 540, no 1-2, p. 120-131Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
ELSEVIER SCIENCE BV, 2018
Keywords
Mixture, Compressibility, Compactibility, Tensile strength, Discrete element method
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-351563 (URN)10.1016/j.ijpharm.2018.02.006 (DOI)000427584900013 ()29425765 (PubMedID)
Available from: 2018-05-30 Created: 2018-05-30 Last updated: 2018-08-20
Hellrup, J., Nordström, J. & Mahlin, D. (2017). Powder compression mechanics of spray-dried lactose nanocomposites. International Journal of Pharmaceutics, 518(1-2), 1-10
Open this publication in new window or tab >>Powder compression mechanics of spray-dried lactose nanocomposites
2017 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 518, no 1-2, p. 1-10Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate the structural impact of the nanofiller incorporation on the powder compression mechanics of spray-dried lactose. The lactose was co-spray-dried with three different nanofillers, that is, cellulose nanocrystals, sodium montmorillonite, and fumed silica, which led to lower micron sized nanocomposite particles with varying structure and morphology. The powder compression mechanics of the nanocomposites and physical mixtures of the neat spray-dried components were evaluated by a rational evaluation method with compression analysis as a tool using the Kawakita equation and the Shapiro-Konopicky-Heckel equation. Particle rearrangement dominated the initial compression profiles due to the small particle sizes of the materials. The strong contribution of particle rearrangement in the materials with fumed silica continued throughout the whole compression profile, which prohibited an in-depth material characterization. However, the lactose/cellulose nanocrystals and the lactose/sodium montmorillonite nanocomposites demonstrated increased yield pressure compared with the physical mixtures indicating increased particle hardness. This increase has likely to do with a reinforcement of the nanocomposite particles by skeleton formation of the nanoparticles. In summary, the rational evaluation applying compression analysis proved to be a valuable tool for mechanical evaluation for this type of materials unless they demonstrate particle rearrangement throughout the whole compression profile.

Keywords
Amorphous, Nanocomposite, Powder compression, Lactose, Spray-drying, Yield pressure
National Category
Materials Chemistry
Identifiers
urn:nbn:se:uu:diva-300156 (URN)10.1016/j.ijpharm.2016.12.041 (DOI)000394402100001 ()28007544 (PubMedID)
Available from: 2016-08-05 Created: 2016-08-03 Last updated: 2018-08-20
Persson, A.-S., Nordström, J., Frenning, G. & Alderborn, G. (2016). Compression analysis for assessment of pellet plasticity: Identification of reactant pores and comparison between Heckel, Kawakita, and Adams equations. Paper presented at 7th International Granulation Workshop, JUN 29-JUL 03, 2015, Sheffield, ENGLAND. Chemical engineering research & design, 110, 183-191
Open this publication in new window or tab >>Compression analysis for assessment of pellet plasticity: Identification of reactant pores and comparison between Heckel, Kawakita, and Adams equations
2016 (English)In: Chemical engineering research & design, ISSN 0263-8762, E-ISSN 1744-3563, Vol. 110, p. 183-191Article in journal (Refereed) Published
Abstract [en]

The issue of accurate derivation of a granule yield stress by the traditional procedure using the Heckel equation in addition to the Kawakita and Adams equations has been addressed. The accuracy of the derived parameters was assessed from comparison of single-particle yield pressures from uniaxial compressions. The single-particle yield pressure was nearly four-fold higher for microcrystalline pellets of low (LP) compared to of high (HP) porosity. Heckel profiles were derived using in situ (in-die) and ex situ (out-of-die) global porosities and ex situ voidage porosities derived from mercury porosimetry of pellets and retrieved pellets from tablets. The voidage Heckel profiles enabled a clear distinction between the LP and HP pellets in contrast to the global Heckel profiles. Thus, the voidage was concluded as a better descriptor of the effective porosity of the reactant pore system than the global porosity for calculations of the Heckel numbers. Due to the challenging and tedious work of deriving precise voidage data, derivation of Kawakita b(-1) and Adams parameters remains an interesting approach for assessing granule plasticity. These clearly differentiated between the HP and LP plasticity, thus suggesting that both parameters can be used as a descriptor of pellet plasticity in analytical powder compression analysis.

Keywords
Compression, Heckel equation, Effective porosity, Plasticity, Kawakita equation, Adams equation
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:uu:diva-300565 (URN)10.1016/j.cherd.2016.01.028 (DOI)000379106600020 ()
Conference
7th International Granulation Workshop, JUN 29-JUL 03, 2015, Sheffield, ENGLAND
Available from: 2016-08-09 Created: 2016-08-09 Last updated: 2018-08-20
Jonsson, H., Gråsjö, J., Nordström, J., Johansson, N. & Frenning, G. (2015). An apparatus for confined triaxial testing of single particles. Powder Technology, 270, 121-127
Open this publication in new window or tab >>An apparatus for confined triaxial testing of single particles
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2015 (English)In: Powder Technology, ISSN 0032-5910, E-ISSN 1873-328X, Vol. 270, p. 121-127Article in journal (Refereed) Published
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.

Keywords
Compression, Triaxial, Single particles, Confined conditions, Apparatus design, Contact mechanics
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-239203 (URN)10.1016/j.powtec.2014.10.016 (DOI)000347579300014 ()
Funder
Swedish Research Council, 621-2011-4049
Available from: 2014-12-19 Created: 2014-12-19 Last updated: 2018-04-12Bibliographically approved
Nordström, J. & Alderborn, G. (2015). The Granule Porosity Controls the Loss of Compactibility for Both Dry- and Wet-Processed Cellulose Granules but at Different Rate. Journal of Pharmaceutical Sciences, 104(6), 2029-2039
Open this publication in new window or tab >>The Granule Porosity Controls the Loss of Compactibility for Both Dry- and Wet-Processed Cellulose Granules but at Different Rate
2015 (English)In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 104, no 6, p. 2029-2039Article in journal (Refereed) Published
Abstract [en]

The aim of this study was to investigate the role of porosity on the compression behavior and tablet tensile strength for granules produced by a dry granulation procedure. Microcrystalline cellulose was used as a typical pharmaceutical excipient and a comparison was made with the effect of granule porosity on the compression behavior and tablet tensile strength of wet-processed granules of the same composition. Both the wet and dry granulation process caused a loss in compactibility of the material that was controlled by the granule porosity up to a critical point of porosity and friability. Above this threshold value of porosity, the granules nearly collapsed completely into primary particles during compression. In these cases, the micro-structure and tensile strength of the formed tablets resembled that of tablets formed from the original ungranulated powder.

Keywords
compaction, compression, granulation, granules, cellulose, porosity, powder technology, tablets, tableting, tensile strength
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:uu:diva-256220 (URN)10.1002/jps.24439 (DOI)000354458800016 ()25872760 (PubMedID)
Available from: 2015-07-06 Created: 2015-06-22 Last updated: 2018-08-20
Mahmoodi, F., Klevan, I., Nordström, J., Alderborn, G. & Frenning, G. (2013). A comparison between two powder compaction parameters of plasticity: The effective medium A parameter and the Heckel 1/K parameter. International Journal of Pharmaceutics, 453(2), 295-299
Open this publication in new window or tab >>A comparison between two powder compaction parameters of plasticity: The effective medium A parameter and the Heckel 1/K parameter
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2013 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 453, no 2, p. 295-299Article in journal (Refereed) Published
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.

Keywords
Powder compression, Compression parameter, Yield stress, Effective medium equation, Heckel equation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-208359 (URN)10.1016/j.ijpharm.2013.06.040 (DOI)000323015800001 ()
Available from: 2013-09-30 Created: 2013-09-30 Last updated: 2017-12-06Bibliographically approved
Nordström, J., Persson, A.-S., Lazorova, L., Frenning, G. & Alderborn, G. (2013). The degree of compression of spherical granular solids controls the evolution of microstructure and bond probability during compaction. International Journal of Pharmaceutics, 442(1-2), 3-12
Open this publication in new window or tab >>The degree of compression of spherical granular solids controls the evolution of microstructure and bond probability during compaction
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2013 (English)In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 442, no 1-2, p. 3-12Article in journal (Refereed) Published
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. 

Keywords
Tablets, Pore structure, Microstructure, Degree of compression, Tensile strength, Percolation theory
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-196531 (URN)10.1016/j.ijpharm.2012.08.011 (DOI)000314690200002 ()
Available from: 2013-03-13 Created: 2013-03-11 Last updated: 2017-12-06Bibliographically approved
Nordstrom, J., Kievan, I. & Alderborn, G. (2012). A protocol for the classification of powder compression characteristics. European journal of pharmaceutics and biopharmaceutics, 80(1), 209-216
Open this publication in new window or tab >>A protocol for the classification of powder compression characteristics
2012 (English)In: European journal of pharmaceutics and biopharmaceutics, ISSN 0939-6411, E-ISSN 1873-3441, Vol. 80, no 1, p. 209-216Article in journal (Refereed) Published
Abstract [en]

In this paper, a structured protocol for powder compression analysis as a test to assess the mechanical properties of particles in a formulation development programme is presented. First, the sequence of classification steps of the protocol is described, and secondly, the protocol is illustrated using compression data of six powders of two model substances, sodium chloride and mannitol. From powder compression data, a set of compression variables are derived, and by using critical values of these variables, the stages expressed during the compression of the powders are identified and the powders are classified into groups with respect to the expression of particle rearrangement, particle fragmentation and particle plastic deformation during compression. It is concluded that the proposed protocol could, in a satisfactorily way, describe and distinguish between the powders regarding their compression behaviour. Hence, the protocol could be a valuable tool for the formulation scientist to comprehensively assess important functionality-related characteristics of drugs and excipients.

Keywords
Classification system, Compression parameters, Heckel, Kawakita, Particle mechanical properties, Powder compression
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-169118 (URN)10.1016/j.ejpb.2011.09.006 (DOI)000299495400027 ()
Available from: 2012-02-27 Created: 2012-02-23 Last updated: 2018-08-20
Nordström, J. & Alderborn, G. (2011). Degree of compression as a potential process control tool of tablet tensile strength. Pharmaceutical development and technology (Print), 16(6), 599-608
Open this publication in new window or tab >>Degree of compression as a potential process control tool of tablet tensile strength
2011 (English)In: Pharmaceutical development and technology (Print), ISSN 1083-7450, E-ISSN 1097-9867, Vol. 16, no 6, p. 599-608Article in journal (Refereed) Published
Abstract [en]

The current view on the development and manufacturing of pharmaceutical preparations points towards improved control tools that can be implemented in pharmaceutical manufacturing as a means to better control end product properties. The objective of this paper was to investigate the relationship between tablet tensile strength and the degree of bed compression in order to evaluate the suitability of assessing the straining of the powder bed during tableting as a process control tool of tablet tensile strength. Microcrystalline cellulose was used as powder raw material and subjected to wet granulation by different procedures to create agglomerates of different physical and compression properties. The produced agglomerates thus showed a large variation in compressibility and compactibility. However, in terms of the relationship between the degree of compression and the tablet tensile strength, all agglomerates gathered reasonably around a single general relationship. The degree of compression hence appears to be a potential valuable process control tool of the tablet tensile strength that may enable the use of an adaptive tableting process with improved product quality consistency.

Keywords
Compaction, compression, engineering strain, granular materials, powder technology, tableting
National Category
Pharmaceutical Sciences
Identifiers
urn:nbn:se:uu:diva-162463 (URN)10.3109/10837450.2010.502177 (DOI)000296652200005 ()
Available from: 2011-12-01 Created: 2011-11-30 Last updated: 2018-08-20
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