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  • 1.
    Ahmed, Hamzah
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Relationship Between Crystal Structure and Mechanical Properties in Cocrystals and Salts of Paracetamol2014Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    Oral tablets are convenient and widely administered drugdosage forms.The mechanical properties of a drug substance such as plasticity, ability to cohere into compacts and friction/adhesion are important in the development of a tablet formulation. Crystal engineering is an interesting and viabletool for improving or optimizing these technical properties of a drug substance.The creation of a lternative polymorphic forms, cocrystals, salts or hydrates of a drug substance can result in structural variations in the molecular packing of the crystals and, thereby, can alter the deformation behavior of the materials.Knowledge of the relationships between crystal modifications and the technical properties in multicomponent systems is limited, but represents a possibility to predict mechanical properties based on crystalstructure that facilitates engineering particles for the optimal processing performance. The overall objective of this thesis is thus to gain better understanding of the relationships between the crystal structure features and the mechanical properties of cocrystals and salts. Paracetamol form I, its cocrystals with oxalic acid and 4,4´-bipyridine, and its hydrochloride salt were selected as model systems in the study.The materials were scaled-up using rational crystallization methods and the physical purity was confirmed. The relevant properties of these powders were determined.Tablets were then made at applied pressures of50-250 MPa under controlled conditions.The tabletability and compactability of the powders were determined. The compression mechanics of the powders were the investigated according to a material classification protocol.Slip planes were identified by visually observing the crystal structures and based on the attachment energies calculated using different force fields in the materialsstudio.The tensile strengths of the powders increased with increasing pressure and the tabletability decreased in the order oxalic acid>paracetamol-hydrochloride salt≈paracetamol-oxalic acid>4,4´-bipyridine>paracetamol-4,4´-bipyridine.The tensile strength of the tablets decreased exponentially with increasing porosity,with some exceptions.Ingeneral, the cocrystals and the salt displayed intermediate compression characteristics as compared to the reference substances.The elastic recovery of the cocrystal and salt forms of paracetamol was not markedly different from that of paracetamol.It was found that slip plane prediction based on the attachment energies was not reliable. While it was possible to explain the improved tableting properties of powders based on the crystal features (i.e. the presence of slip planes and flat layers), no clear relationship was found with yield pressure. This may be attributed to possible brittle material characteristics and the surface energies of the crystals,which need to be further studied.Thus, cocrystallization and salt formation introduced structural features that were responsible for changes in the compaction and compression properties of drug substances. In future work, we intend to extend these studies to provide a clear picture of structure-mechanical property relationships in organic molecular crystals over multiple length scales;molecules to crystals to bulk powder.Key words Crystal engineering, solid forms, cocrystals, salts, tableting, crystal structure, mechanical properties, compression analysis

  • 2.
    Ahmed, Hamzah
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Shimpi, Manishkumar R.
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Chemical Engineering.
    Velaga, Sitaram P.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Relationship between mechanical properties and crystal structure in cocrystals and salt of paracetamol2017In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 43, no 1, p. 89-97Article in journal (Refereed)
    Abstract [en]

    Objectives were to study mechanical properties of various solid forms of paracetamol and relate to their crystal structures. Paracetamol Form I (PRA), its cocrystals with oxalic acid (PRA-OXA) and 4,4-bipyridine (PRA-BPY) and hydrochloride salt (PRA-HCL) were selected. Cocrystals and salt were scaled-up using rational crystallization methods. The resulting materials were subjected to differential scanning solid-state characterization. The powders were sieved and 90-360 µm sieve fraction was considered. These powders were examined by scanning electron microscopy (SEM) and densities were determined. Tablets were made at applied pressures of 35-180 MPa under controlled conditions and the tablet height, diameter and hardness were measured. Tensile strength and porosity of the tablets were estimated using well known models. Crystal structures of these systems were visualized and slips planed were identified. Cocrystal and salt of PRA were physically pure. Sieved powders had comparable morphologies and particle size. The apparent and theoretical densities of powders were similar but no clear trends were observed. The tensile strengths of these compacts were increased with increasing pressure whereas tabletability decreased in the order oxalic acid > PRA-HCL ≈ PRA-OXA > BPY > PRA-BPY. Tablet tensile strength decreases exponentially with increasing porosity with the exception of PRY-BPY and BPY. Slip plane prediction based on attachment energies may not be independently considered. However, it was possible to explain the improved mechanical properties of powders based on the crystal structure. Cocrystallization and salt formation have introduced structural features that are responsible for improved tableting properties of PRA.

  • 3.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Backman, Ylva
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Bergmark, Ulrika
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Gardelli, Åsa
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Hertting, Krister
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    ”Det ska vara kul att lära!”: Skolan som den bästa platsen för lärande2012In: Forskning om undervisning och lärande, ISSN 2000-9674, E-ISSN 2001-6131, Vol. 8, p. 41-49Article in journal (Other (popular science, discussion, etc.))
    Abstract [sv]

    Inom ramen för denna artikel diskuterar vi såväl den psykosociala som den fysiska miljön i skolan. Vidare argumenterar vi för att skolans miljö är av betydelse för elevernas möjligheter att lära sig, likväl som för deras upplevelser av lärandesituationerna. Särskilt intressant blir då att lyssna till eleverna. Syftet med denna artikel är därför att synliggöra och diskutera elevers röster i förhållande till hur skolan kan bli den bästa platsen för lärande. Detta görs med utgångspunkt i forskningsprojektet ”Skolan suger” eller?, där drygt 200 elever i åldrarna 11–15 år deltog. Eleverna fick skriftligen reflektera över hur skolan ska bli en riktigt bra lärandemiljö. För att utveckla skolan till den bästa platsen för lärande uttryckte eleverna en önskan att kunna påverka sin lärandemiljö, att uppnå ömsesidighet och samspel, att kunna hantera tidsregleringen i skolan, samt att uppfylla behov för välbefinnande.

  • 4.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Backman, Ylva
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Bergmark, Ulrika
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Gardelli, Åsa
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Hertting, Krister
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    ”Skolan suger” ... eller?: Att ge röst åt barns och ungdomars erfarenheter av psykosocial hälsa i sin lärandemiljö2012In: Resultatdialog 2012, Stockholm: Vetenskapsrådet , 2012, p. 9-15Chapter in book (Other (popular science, discussion, etc.))
  • 5.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Bergmark, Ulrika
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Forsman, Arne
    Hertting, Krister
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Lasten hyvinvointi ell – näkökulmia aiheeseen2008In: Psykososiaalisen hyvinvoinnin edistäminen opetustyössä, Rovaniemi: Lapin yliopistokustannus , 2008, p. 39-46Chapter in book (Other academic)
  • 6.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Bergmark, Ulrika
    Forsman, Arne
    Hertting, Krister
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Några perspektiv på psykosocial hälsa bland barn2008In: Barns trivsel i Nord: aktiviteter for psykososial trivsel fra skoler i Barentsregionen, Oslo: Gyldendal Norsk Folag AS , 2008, p. 39-45Chapter in book (Other academic)
  • 7.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Bergmark, Ulrika
    Forsman, Arne
    Hertting, Krister
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Well-being among children: some perspectives from a Swedish viewpoint2008In: Crystals of schoolchildren's well-being: cross-border training material for promoting psychosocial well-being through school education, Rovaniemi: Lapland University of Applied Sciences, 2008, p. 39-46Chapter in book (Other academic)
  • 8.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    A silent message is also a message2005In: A Nordic dimension in education and research - myth or reality?: NFPF/NERA 33rd congress, 2005, p. 83-Conference paper (Other academic)
    Abstract [en]

    "Dammed taxi cab!" A twelve year old student wrote these words in the margins of a questionnaire in school concerning psychosocial well-being. Within this paper they will serve as a point of departure for the discussion. Can the messages found on the sides of the squares intended for an X in a questionnaire be considered non-messages? Or are these expressions indeed messages that are made silent and therefore can be considered silent messages? Then one might wonder what the meanings of the silent messages are that often occurs in questionnaires? Can, or maybe should, we take notice of these silent messages? According to Polanyi every human being has silent and unexpressed dimensions within themselves, which acknowledge situations where we recognise that we know more than we can explain. This is also stressed by Merleau-Ponty, who argued that something exists beyond what is said, and Bateson emphasised that a non-message is also a message - the silence tells us something. Within this paper we will highlight and discuss the significance of silent messages of communication in general, and especially in questionnaires.

  • 9.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehabilitation.
    Beyond the boundaries of the classroom: Interpersonal relationships in thetransformation from (edu)room to (edu)roam2018In: NERA2018 - 46th Congress: Educational Research: Boundaries, Breaches and Bridges, 2018Conference paper (Refereed)
  • 10.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    'Dammed taxi cab': how silent communication in questionnaires can be understood and used to give voice to children's experiences2011In: International Journal of Research and Method in Education, ISSN 1743-727X, E-ISSN 1743-7288, Vol. 34, no 2, p. 117-130Article in journal (Refereed)
    Abstract [en]

    'Dammed taxi cab' - a 12-year-old boy wrote these words in the margins of a questionnaire, and within this paper they will serve as a point of departure for the discussion of the use of questionnaires as a way to voice children's experiences. The overall aim of this paper is to enable understanding of and discuss the use of questionnaires as a way to voice children's experiences. An analysis in accordance with a life-world approach has provided the lens through which to explore messages that can occur in questionnaires. The key research questions that will be explored in an attempt to answer the overall aim are: (i) how can unanswered questions and notes in the margins of a questionnaire be understood? and (ii) why is a questionnaire not always completed, according to the intention of its creators? To develop an understanding of this we analysed a number of questionnaires with unanswered questions and notes in the margins using a life-world approach. During the analysis two themes emerged: silent messages and messages being silenced. Finally, we discuss the legitimacy of questionnaires in childhood research and possible implications for practice when using this method to give voice to children's experiences.

  • 11.
    Alerby, Eva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Silence for health and learning: a phenomenological reflection2011Conference paper (Other academic)
  • 12.
    Alexandrou, Constantia
    et al.
    Department of Physics, University of Cyprus.
    Constantinou, Martha
    Department of Physics, University of Cyprus.
    Korzec, Tomasz
    Institut fur Physik, Humboldt Universitat zu Berlin.
    Panagopoulos, Haralambos G.
    Department of Physics, University of Cyprus.
    Stylianou, Fotos
    Department of Physics, University of Cyprus.
    Renormalization constants for 2-twist operators in twisted mass QCD2011In: Physical Review D. Particles and fields, ISSN 0556-2821, E-ISSN 1089-4918, Vol. 83, no 1, article id 014503Article in journal (Refereed)
    Abstract [en]

    Perturbative and nonperturbative results on the renormalization constants of the fermion field and the twist-2 fermion bilinears are presented with emphasis on the nonperturbative evaluation of the one-derivative twist-2 vector and axial-vector operators. Nonperturbative results are obtained using the twisted mass Wilson fermion formulation employing two degenerate dynamical quarks and the tree-level Symanzik improved gluon action. The simulations have been performed for pion masses in the range of about 450-260 MeV and at three values of the lattice spacing a corresponding to β=3.9, 4.05, 4.20. Subtraction of O(a2) terms is carried out by performing the perturbative evaluation of these operators at 1-loop and up to O(a2). The renormalization conditions are defined in the RI⊃′-MOM scheme, for both perturbative and nonperturbative results. The renormalization factors, obtained for different values of the renormalization scale, are evolved perturbatively to a reference scale set by the inverse of the lattice spacing. In addition, they are translated to MS̄ at 2 GeV using 3-loop perturbative results for the conversion factors

  • 13.
    Alexandrou, Constantia
    et al.
    Department of Physics, University of Cyprus.
    Constantinou, Martha
    Department of Physics, University of Cyprus.
    Korzec, Tomasz
    Institut fur Physik, Humboldt Universitat zu Berlin.
    Panagopoulos, Haralambos G.
    Department of Physics, University of Cyprus.
    Stylianou, Fotos
    Department of Physics, University of Cyprus.
    Renormalization constants of local operators for Wilson type improved fermions2012In: Physical Review D. Particles and fields, ISSN 0556-2821, E-ISSN 1089-4918, Vol. 86, no 1, article id 014505Article in journal (Refereed)
    Abstract [en]

    Perturbative and nonperturbative results are presented on the renormalization constants of the quark field and the vector, axial-vector, pseudoscalar, scalar, and tensor currents. The perturbative computation, carried out at one-loop level and up to second order in the lattice spacing, is performed for a fermion action, which includes the clover term and the twisted mass parameter yielding results that are applicable for unimproved Wilson fermions, as well as for improved clover and twisted mass fermions. We consider ten variants of the Symanzik improved gauge action corresponding to ten different values of the plaquette coefficients. Nonperturbative results are obtained using the twisted mass Wilson fermion formulation employing two degenerate dynamical quarks and the tree-level Symanzik improved gluon action. The simulations are performed for pion masses in the range of 480-260 MeV and at three values of the lattice spacing, a, corresponding to β=3.9, 4.05, 4.20. For each renormalization factor computed nonperturbatively we subtract its perturbative O(a2) terms so that we eliminate part of the cutoff artifacts. The renormalization constants are converted to MS̄ at a scale of μ=2GeV. The perturbative results depend on a large number of parameters and are made easily accessible to the reader by including them in the distribution package of this paper, as a Mathematica input file.

  • 14.
    Alhalaweh, Amjad
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Pharmaceutical cocrystals: formation mechanisms, solubility behaviour and solid-state properties2012Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The primary aim of pharmaceutical materials engineering is the successful formulation and process development of pharmaceutical products. The diversity of solid forms available offers attractive opportunities for tailoring material properties. In this context, pharmaceutical cocrystals, multicomponent crystalline materials with definite stoichiometries often stabilised by hydrogen bonding, have recently emerged as interesting alternative solid forms with potential for improving the physical and biopharmaceutical properties of a drug substance. There are, however, gaps in our understanding of the screening, scale-up and formulation operations required for effective use of cocrystals in drug product development. The objective of this thesis was to improve fundamental understanding of the formation mechanisms, solution behaviour and solid-state properties of pharmaceutical cocrystals. The solution chemistry and solubility behaviour of a diverse set of cocrystals were studied. It was found that the thermodynamic stability regions of the cocrystals and their components were defined by the phase solubility diagrams. Spray drying was introduced as a new method of preparing cocrystals; the formation mechanisms are illustrated. The cocrystals were more soluble than the respective drugs alone and the solubility-pH profiles were able to be predicted by mathematical models using a eutectic point determination approach. The cocrystal solubility was pH-dependent and could be engineered by the choice of coformers; this is valuable information for designing robust formulations. The solubility advantage of cocrystals was retained by the use of excipients that imparted kinetic and thermodynamic stability. The retention of drug-coformer association in processed cocrystals has been revealed, introducing a novel concept with potential implications for solid dosage form development. The final study demonstrated that the structure of the crystals and the particle engineering processes affected the solidstate and bulk particle properties of the cocrystals.This thesis contributes to the field of pharmaceutical science by advancing our understanding of crystallization processes and formulation development, thus enabling pharmaceutical cocrystals into drug products.

  • 15. Alhalaweh, Amjad
    et al.
    Ali, Hassan
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Effects of polymer and surfactant on the dissolution and transformation profiles of cocrystals in aqueous media2014In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 14, no 2, p. 643-648Article in journal (Refereed)
    Abstract [en]

    Capturing solubility advantages of cocrystals is of great interest, and thus to understand the mechanism by which different excipients could maintain the supersaturation generated by cocrystals at the course of absorption in aqueous media is essential. To achieve this aim, the impact of different excipients on dissolution behavior of indomethacin-saccharin (IND-SAC) were monitored by measuring the concentrations of cocrystal components in the absence and presence of various concentration of excipients by HPLC, and solid phases were analyzed by differential scanning calorimetry after each experiment and the potential of Raman spectroscopy for monitoring phase transformations in situ was tested. No dissolution advantage was offered by cocrystals in the absence of any solution additive. The polymer and surfactant used in the study increased the solubility of IND but not SAC. This differential solubilization effect is believed to have stabilized the cocrystals for a relevant period for the absorption to take place. This could be attributed to either decreased gap between supersaturation and saturation of the drug or drug interaction with the additives. Understanding the effects of excipients type and concentration on the transformation profile is vital for designing enabling formulations for cocrystals. The eutectic constant may be useful in selecting excipients for stabilizing cocrystals.

  • 16.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Alzghoul, Ahmad
    Luleå University of Technology, Department of Engineering Sciences and Mathematics, Product and Production Development.
    Kaialy, Waseem
    Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent.
    Data mining of solubility parameters for computational prediction of drug–excipient miscibility2014In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 40, no 7, p. 904-909Article in journal (Refereed)
    Abstract [en]

    Computational data mining is of interest in the pharmaceutical arena for the analysis of massive amounts of data and to assist in the management and utilization of the data. In this study, a data mining approach was used to predict the miscibility of a drug and several excipients, using Hansen solubility parameters (HSPs) as the data set. The K-means clustering algorithm was applied to predict the miscibility of indomethacin with a set of more than 30 compounds based on their partial solubility parameters [dispersion forces , polar forces and hydrogen bonding ]. The miscibility of the compounds was determined experimentally, using differential scanning calorimetry (DSC), in a separate study. The results of the K-means algorithm and DSC were compared to evaluate the K-means clustering prediction performance using the HSPs three-dimensional parameters, the two-dimensional parameters such as volume-dependent solubility and hydrogen bonding , and selected single (one-dimensional) parameters. Using HSPs, the prediction of miscibility by the K-means algorithm correlated well with the DSC results, with an overall accuracy of 94%. The prediction accuracy was the same (94%) when the two-dimensional parameters or the hydrogen-bonding (one-dimensional) parameter were used. The hydrogen-bonding parameter was thus a determining factor in predicting miscibility in such set of compounds, whereas the dispersive and polar parameters had only a weak correlation. The results show that data mining approach is a valuable tool for predicting drug–excipient miscibility because it is easy to use, is time and cost-effective, and is material sparing.

  • 17.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    George, Sumod
    Basavoju, Srinivas
    Childs, S.L.
    Renovo Research, Atlanta, GA.
    Rizvi, S.A.A.
    College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Pharmaceutical cocrystals of nitrofurantoin: Screening, characterization and crystal structure analysis2012In: CrystEngComm, ISSN 1466-8033, E-ISSN 1466-8033, Vol. 14, no 15, p. 5078-5088Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to screen and prepare cocrystals of the poorly soluble drug nitrofurantoin (NTF) with the aim of increasing its solubility. Screening for cocrystals of NTF using 47 coformers was performed by high-throughput (HT) screening using liquid assisted grinding (LAG) methods. Raman spectroscopy and powder X-ray diffraction (PXRD) were used as the primary analytical tools to identify the new crystalline solid forms. Manual LAG and reaction crystallization (RC) experiments were carried out to confirm and scale-up the hits. Seven hits were confirmed to be cocrystals. The cocrystals were characterized by PXRD, Raman and IR spectroscopy, thermal analysis (DSC and TGA) and liquid-state NMR or elemental analysis. The solution stability of the scaled-up cocrystals in water was tested by slurrying the cocrystals at 25 °C for one week. NTF forms cocrystals with a 1:1 stoichiometric ratio with urea (1), 4-hydroxybenzoic acid (2), nicotinamide (3), citric acid (4), l-proline (5) and vanillic acid (6). In addition, NTF forms a 1:2 cocrystal with vanillin (7). All but one of the NTF cocrystals transformed (dissociated) in water, resulting in NTF hydrate crystalline material or NTF hydrate plus the coformer, which indicates that the transforming cocrystals have a higher solubility than the NTF hydrate under these conditions. The crystal structures of 1:1 NTF-citric acid (4) and 1:2 NTF-vanillin (7) were solved by single-crystal X-ray diffraction. The crystal structures of these two cocrystals were analyzed in terms of their supramolecular synthons.

  • 18.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    George, Sumod
    Boström, Dan
    Department of Energy Technology and Thermal Process Chemistry, Umea University.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    1:1 and 2:1 urea-succinic acid cocrystals: structural diversity, solution chemistry, and thermodynamic stability2010In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 10, no 11, p. 4847-4855Article in journal (Refereed)
    Abstract [en]

    The aim of this work was to study the crystal structures of 1:1 and 2:1 urea-succinic acid (U-SA) cocrystals and to investigate the role of solution chemistry in the formation and stability of different stoichiometric cocrystals. The structural diversity of other urea-dicarboxylic acid cocrystals is also discussed. The 1:1 U-SA cocrystal was stabilized by an acid-amide heterosynthon while acid-amide heterosynthons and amide-amide homosynthons stabilized the 2:1 cocrystals. The hydrogen bonding motifs in 1:1 and 2:1 U-SA cocrystals were consistent with other urea-dicarboxylic acid systems with similar stoichiometries. The 1:1 cocrystals were transformed to 2:1 cocrystals upon slurrying in various solvents at 25 °C. The phase solubility diagram was used to define the stability regions of different solid phases in 2-propanol at 25 °C. While no phase stability region for 1:1 cocrystal could be found, the stable regions for the 2:1 cocrystals and their pure components were defined by eutectic points. The solubility of the 2:1 cocrystals was dependent on the concentration of the ligand in the solution and explained by the solubility product and 1:1 solution complexation. The mathematical models predicting the solubility of the 2:1 cocrystals were evaluated and found to fit the experimental data

  • 19.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Kaialy, Waseem
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Buckton, Graham
    Department of Pharmaceutics, School of Pharmacy, University College London.
    Gill, Hardyal
    Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent.
    Nokhodchi, Ali
    Chemistry and Drug Delivery Group, Medway School of Pharmacy, University of Kent.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Theophylline cocrystals prepared by spray drying: physicochemical properties and aerosolization performance2013In: AAPS PharmSciTech, ISSN 1530-9932, E-ISSN 1530-9932, Vol. 14, no 1, p. 265-276Article in journal (Refereed)
    Abstract [en]

    The purpose of this work was to characterize theophylline (THF) cocrystals prepared by spray drying in terms of the physicochemical properties and inhalation performance when aerosolized from a dry powder inhaler. Cocrystals of theophylline with urea (THF-URE), saccharin (THF-SAC) and nicotinamide (THF-NIC) were prepared by spray drying. Milled THF and THF-SAC cocrystals were also used for comparison. The physical purity, particle size, particle morphology and surface energy of the materials were determined. The in vitro aerosol performance of the spray-dried cocrystals, drug-alone and a drug-carrier aerosol, was assessed. The spray-dried particles had different size distributions, morphologies and surface energies. The milled samples had higher surface energy than those prepared by spray drying. Good agreement was observed between multi-stage liquid impinger and next-generation impactor in terms of assessing spray-dried THF particles. The fine particle fractions of both formulations were similar for THF, but drug-alone formulations outperformed drug-carrier formulations for the THF cocrystals. The aerosolization performance of different THF cocrystals was within the following rank order as obtained from both drug-alone and drug-carrier formulations: THF-NIC > THF-URE > THF-SAC. It was proposed that micromeritic properties dominate over particle surface energy in terms of determining the aerosol performance of THF cocrystals. Spray drying could be a potential technique for preparing cocrystals with modified physical properties.

  • 20.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Roy, Lilly
    Department of Pharmaceutical Sciences, University of Michigan.
    Rodriguez-Hornedo, Nair
    Department of Pharmaceutical Sciences, University of Michigan.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    pH-dependent solubility of indomethacin-saccharin and carbamazepine-saccharin cocrystals in aqueous media2012In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392, Vol. 9, no 9, p. 2605-2612Article in journal (Refereed)
    Abstract [en]

    Cocrystals constitute an important class of pharmaceutical solids for their remarkable ability to modulate solubility and pH dependence of water insoluble drugs. Here we show how cocrystals of indomethacin-saccharin (IND-SAC) and carbamazepine-saccharin (CBZ-SAC) enhance solubility and impart a pH-sensitivity different from that of the drugs. IND-SAC exhibited solubilities 13 to 65 times higher than IND at pH values of 1 to 3, whereas CBZ-SAC exhibited a 2 to 10 times higher solubility than CBZ dihydrate. Cocrystal solubility dependence on pH predicted from mathematical models using cocrystal K(sp), and cocrystal component K(a) values, was in excellent agreement with experimental measurements. The cocrystal solubility increase relative to drug was predicted to reach a limiting value for a cocrystal with two acidic components. This limiting value is determined by the ionization constants of cocrystal components. Eutectic constants are shown to be meaningful indicators of cocrystal solubility and its pH dependence. The two contributions to solubility, cocrystal lattice and solvation, were evaluated by thermal and solubility determinations. The results show that solvation is the main barrier for the aqueous solubility of these drugs and their cocrystals, which are orders of magnitude higher than their lattice barriers. Cocrystal increase in solubility is thus a result of decreasing the solvation barrier compared to that of the drug. This work demonstrates the favorable properties of cocrystals and strategies that facilitate their meaningful characterization.

  • 21.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Sokolowski, Anders
    Department of Pharmaceutical Chemistry, Uppsala University.
    Rodriguez-Hornedo, Nair
    Department of Pharmaceutical Sciences, University of Michigan.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Solubility behavior and solution chemistry of indomethacin cocrystals in organic solvents2011In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 11, no 9, p. 3923-3929Article in journal (Refereed)
    Abstract [en]

    The main objective of this study was to investigate the solubility behavior and solution chemistry of indomethacin-saccharin (IND-SAC) cocrystals in organic media. We also evaluated previously proposed models of cocrystal solubility in organic solvents. In addition, the solubility behavior of IND-SAC cocrystals was compared with that of indomethacin-nicotinamide (IND-NIC) cocrystals using the eutectic constant approach. Phase solubility diagrams of IND-SAC cocrystals in various solvents were generated and the transition concentrations, at which drug and cocrystals are in equilibrium with the solvents, were determined. The solubility of IND-SAC cocrystals was explained by the solubility product and solution complexation. The tested models were found to fit the experimental data and to adequately explain the solubility behavior of the cocrystals. The solution complexation of IND and SAC is negligible in ethyl acetate and low in methanol and ethanol. The IND-NIC cocrystals were more soluble than the IND-SAC cocrystals in all the solvents studied. The eutectic constants predicted both the solubility and the stability of the cocrystals. Understanding the solubility behavior and solution chemistry of cocrystals has important implications for the screening, scale-up, and formulation development of this solid form. Further, the determination of eutectic constants is a simple and resource sparing means of obtaining key information on cocrystal stability and solution behavior

  • 22.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Formation of cocrystals by spray drying2010In: Journal of Pharmacy and Pharmacology (JPP), ISSN 0022-3573, E-ISSN 2042-7158, Vol. 62, no 10 - Special issue, p. 1332-1333Article in journal (Other academic)
    Abstract [en]

    Spray drying is a widely used technique for material processing and scale-up. The cocrystals formation by spray drying is studied. In contrast to solvent evaporation method, spray drying of stiochiometric solutions of incongruently saturating cocrystals had generated pure cocrystals. The formation phenomena in spray drying could be kinetically controlled or mediated by glassy state.

  • 23.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Formation of cocrystals from stoichiometric solutions of incongruently saturating systems by spray drying2010In: Crystal Growth & Design, ISSN 1528-7483, E-ISSN 1528-7505, Vol. 10, no 8, p. 3302-3305Article in journal (Refereed)
    Abstract [en]

    Spray drying is a well established technique for material processing and scale-up. This study investigated the formation of pharmaceutical cocrystals by spray drying. The cocrystal formation mechanisms in spray-drying and solution methods, based on triangular phase diagrams, are discussed. The solvent evaporation of stoichiometric solutions of incongruently saturating cocrystals resulted in a mixture of phases, as dictated by the thermodynamic phase diagram. In contrast, spray drying of similar solutions of incongruently saturating systems generated pure cocrystals. It is thus suggested that the formation of cocrystals by spray drying could be kinetically controlled and/or mediated by the glassy state of the material.

  • 24.
    Alhalaweh, Amjad
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Vilinska, Annamaria
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Gavini, Elisabetta
    University of Sassari.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Rassu, Giovanna
    University of Sassari.
    Surface thermodynamics of mucoadhesive dry powder formulation of zolmitriptan2011In: AAPS PharmSciTech, ISSN 1530-9932, E-ISSN 1530-9932, Vol. 12, no 4, p. 1186-1192Article in journal (Refereed)
    Abstract [en]

    Microparticle powders for nasal delivery were formulated to contain the model drug, zolmitriptan, and varying proportions of different polymers. The objective of the study was to investigate the effects of these formulative parameters on the surface chemistry of the spray-dried microparticles and their potential for adhesion to the tested substrates, porcine mucin, and nasal tissue. The polymers used were chitosans of varying ionization states and molecular weights and hydroxypropyl methyl cellulose. The surface energies of the surfaces of the microparticles were determined using contact angle measurements and the van Oss model. The theory of surface thermodynamics was applied to determine the theoretical potential for the different materials to adhere to the substrates. It was found that the drug or polymers alone, as well as the various formulations, were more likely to adhere to mucin than to nasal tissue. Further, there was a trend for higher molecular weight chitosans to adhere better to the substrates than lower molecular weight chitosans. Similarly, adhesion was improved for formulations with a higher content of polymers. These theoretical predictions may be compared with further experimental results and be of use in making informed decisions on the choice of formulations for future expensive bio-studies.

  • 25.
    AlHayali, Amani
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    In vitro-solubility and supersaturation behavior of supersaturating drug delivery systems2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The development of new pharmaceutical products has been challenged by the growing number of poorly water-soluble drugs, which often lead to suboptimal bioavailability. Various approaches, such as the use of amor-phous solid dispersions and cocrystals, have been used to improve the solu-bility, and subsequent bioavailability, of these drug molecules. Supersaturat-ing drug delivery systems (SDDSs) have potential for achieving adequate oral drug bioavailability by increasing the drug solubility and creating a su-persaturated state in the gastrointestinal tract. However, there is a need for better understanding of the supersaturation behavior in SDDSs and of the factors affecting supersaturation. The main objective of this thesis was to improve understanding of the supersaturation solubility behavior in SDDSs with a particular focus on rapidly dissolving solid forms (amorphous forms/cocrystals).

    In the course of the work, a new formulation for ezetimibe using an amorphous solid dispersion was prepared, cocrystals of tadalafil were pre-pared, and oral films of silodosin were formulated for the first time. These new formulations were thoroughly characterized using a number of solid-state and pharmaceutical characterization techniques.

    The dissolution and supersaturation behavior of the prepared SDDSs were studied. The effects of various factors on the supersaturation and precipita-tion characteristics were investigated. These factors included the preparation method, the temperature of the dissolution medium, the type of dissolution biorelevant medium (gastric/intestinal) used, the permeability of the relevant gastrointestinal membranes, the addition of polymers, and the addition of surfactants. The amorphous solid dispersions, cocrystals and oral films that were prepared represent new drug formulations that provide significantly higher dissolution rates and supersaturated solubility than crystalline drug forms. Solid dispersions prepared by the melting method had better super-saturation properties than those prepared by spray drying. The precipitation kinetics of the solid dispersion were faster at 37 ̊C than at 25 ̊C in bio-relevant media. Implementation of an absorption tool during in vitro evalua-tion of supersaturation levels could improve the prediction accuracy of su-persaturation and precipitation. A better understanding of the effects of ex-cipients on the supersaturation and precipitation behavior of these types of formulation was obtained in this thesis. The improvement in supersaturation solubility obtained by adding polymers and surfactants was not proportional to the amounts of excipient used.

    This thesis has made notable contributions to the field of pharmaceutical science by advancing our understanding of the supersaturation solubility behavior of the newly prepared SDDSs.

  • 26.
    Al-Hayali, Amani Ibraheem Younis
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Tavelin, Staffan
    Umeå university.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Dissolution and precipitation behavior of ternary solid dispersions of Ezetimibe in biorelevant media: AAPS annual meeting and Exposition2014 USA2014Conference paper (Other academic)
    Abstract [en]

    PurposeTo prepare ternary solid dispersions of Ezetimibe (EZ) and investigate their powder dissolution and precipitation behavior(supersaturation) in simulated gastric and intestinal fluidsMethodsTernary solid dispersions of EZ were prepared with PVPK30 and Poloxamer 188 at different ratios. Spray drying and meltquenching methods were used for the preparation of these solid dispersions. The solid dispersions were characterized bybasic to advanced solid-state tools including Modulated differential scanning calorimetry (MDSC), Powder X-ray diffractionand Fourier transform infrared spectroscopy .Biorelevant simulated media (FaSSIF pH 6.5 and FaSSGF pH1.6) were used tostudy the supersaturating solubility of the ternary solid dispersions. HPLC was used to determine the drug concentrationsResultsTernary solid dispersions were successfully prepared by spray drying and melt quench methods. All prepared soliddispersions showed broadening of the XRD peaks indicating amorphous nature. MDSC analysis revealed disappearance ofthe melting peak of Ezetimibe indicating that molecular dispersion of the drug in polymer matrix. The solid dispersions withhigher PVPK30 content showed single Tg at 158.54 °C (spray drying) and 169.32 °C (melt quench). About 10 folds increasein the apparent solubility was observed for solid dispersions prepared by both methods. However, melt quenched soliddispersions had maintained the supersaturation solubility in FaSSIF longer than spray dried solid dispersions. Dissolutionstudies in FaSSGF are ongoingConclusionAmorphous ternary solid dispersions of Ezetimibe containing PVP K30 and Poloxamer 188 could be prepared by spraydrying and melt quenching methods. These solid dispersions showed improved solubility and prolonged supersaturation inbiorelevant media

  • 27.
    Al-Hayali, Amani Ibraheem Younis
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Tavellin, Staffan
    Departments of Pharmacology and Clinical Neuroscience, Umeå university.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media2017In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 43, no 1, p. 79-88Article in journal (Refereed)
    Abstract [en]

    The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25˚C and 37˚C) were investigated in this work. Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry, modulated differential scanning calorimetry, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions. All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25˚C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried solid (SD) dispersions and supersaturation was maintained. However, at 37˚C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures. Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25˚C may not predict the supersaturation behavior at physiologically relevant temperatures.  

  • 28.
    AlHayali, Amani
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Selo, Mohammed Ali
    School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin; Faculty of Pharmacy, University of Kufa, Al-Najaf, Iraq.
    Ehrhardt, Carsten
    School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Investigation of supersaturation and in vitro permeation of the poorly water soluble drug ezetimibe2018In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 117, p. 147-153Article in journal (Refereed)
    Abstract [en]

    The interplay between supersaturation, precipitation and permeation characteristics of the poorly water-soluble drug ezetimibe (EZ) was investigated. Supersaturation and precipitation characteristics of EZ in the presence of Caco-2 cells were compared to those in a cell-free environment. The effect of the water-soluble polymer polyvinyl pyrrolidone (PVP-K30) on the supersaturation, precipitation and transport of EZ was also investigated and the amount of drug taken up by Caco-2 cells was quantified.

    A one-compartment setup without Caco-2 cells (i.e. in the wells of cell-culture plates) was used to mimic a non-sink in vitro dissolution chamber. The two-compartment Caco-2 cell monolayer setup (with apical and basolateral compartments) was used to investigate how the absorption of EZ affects supersaturation. EZ in varying degrees of supersaturation (DS; 10, 20, 30 and 40) was introduced into the one-compartment setup or the apical chamber of the two-compartment setup. Samples were collected at specific times to determine supersaturation, precipitation and permeation. At the end of the study, Caco-2 cells were lysed and the intracellular amount of EZ was quantified.

    In the one-compartment setup, a high DS was associated with rapid precipitation. Supersaturation was maintained for longer time periods and precipitation was lower in the presence of Caco-2 cells. There were no significant differences in the absorption rate of the drug, even at high concentrations on the apical side. Permeability coefficients for all supersaturated solutions (i.e. DS 10–40) were significantly (p < 0.05) different from those when EZ was present in crystalline form. Both concentrations of PVP-K30 (i.e. 0.05% and 0.1% w/v) improved solubility and supersaturation of EZ when added to the apical side, however, the increase in absorption at the higher concentration was not proportional. The amount of intracellular EZ increased with increasing DS in the apical side, until the saturation limit was reached in the cells (i.e. at DS 30 and higher).

    This study demonstrated that precipitation of EZ could be overestimated when supersaturation was investigated without the implementation of an absorption compartment in vitro, both in the absence and in the presence of polymer.

  • 29.
    Al-Hayali, Amani
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Selo, Mohammed Ali
    School of Pharmacy and Pharmaceutical Sciences , Trinity College Dublin .
    Ehrhardt, Carsten
    School of Pharmacy and Pharmaceutical Sciences , Trinity College Dublin .
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Investigation of supersaturation and permeation of a poorly water soluble drug Ezetimibe: Systems approaches to drug discovery, development and clinical usage2017In: Future Medicines For One World, 2017Conference paper (Refereed)
  • 30.
    Ali, Hassan
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Alhalaweh, Amjad
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Mendes, N.F.C.
    Ribeiro-Claro, Paulo
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Solid-state vibrational spectroscopic investigation of cocrystals and salt of indomethacin2012In: CrystEngComm, ISSN 1466-8033, E-ISSN 1466-8033, Vol. 14, no 20, p. 6665-6674Article in journal (Refereed)
    Abstract [en]

    Knowledge and control of the solid forms of active pharmaceutical ingredients are important aspects of drug development in the pharmaceutical industry. In this paper, the process of the molecular self-assembly of saccharin cocrystals and the 2-amino-5-methylpyridine salt of indomethacin, in terms of the hydrogen bonding patterns, has been studied in the solid-state using vibrational spectroscopy (Raman and infrared). Interaction patterns in the respective crystalline states were obtained from the single crystal data. The effects of cocrystal and salt formation on the frequencies of the vibrational modes of motion were explained by vibrational spectroscopy and supported by quantum chemical calculations at the density functional theory level, leading to unambiguous assignment of the vibrational spectra of the starting materials and their respective products. Both Raman and infrared spectroscopies were useful, reliable tools for characterizing and distinguishing the indomethacin cocrystals and salt.

  • 31.
    Ali, Hassan
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Alhalaweh, Amjad
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Vibrational spectroscopic investigation of polymorphs and cocrystals of indomethacin2013In: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 39, no 5, p. 625-634Article in journal (Refereed)
    Abstract [en]

    Context:Identification of optimal solid form of an active pharmaceutical ingredient and form control are very important in drug development. Thus, the structural information of these forms and in-depth insight on the modes of molecular interactions are necessary, and vibrational spectroscopic methods are well suited for this purpose.Objective:In-depth structural analysis of different solid forms of indomethacin (IND) using Raman and infrared (IR) spectroscopy is the objective. We have investigated the modes of molecular interactions in polymorphs (α and γ), amorphous and discovered cocrystals of IND with nicotinamide (NIC) and trans-cinnamic acid (CIN) coformers.Materials and methods: The solid forms of IND have been prepared; their purity has been verified by differential scanning calorimetry and powder X-ray diffractometry and then studied in the solid-state by Raman and IR spectroscopy. The modes of the interactions were closely investigated from the vibrational data.Results: The key vibrational features of IND solid forms have been specified. The IR (C=O) band at 1713 cm−1 attributed to cyclic acid dimer of γ IND has disappeared in IND–NIC/CIN whilst retained in IND–SAC cocrystal.Discussion:IND cocrystallizes in different conformations and crystal lattices with different coformers. The cyclic acid dimer of IND has been kept on its cocrystallization with saccharin and it could have been broken with NIC and CIN.Conclusions: The complementary nature of Raman and IR spectroscopy allowed unambiguous investigation of the chemical composition of pharmaceutical materials which is of particular importance in the absence of detailed structural information, as in the case of IND–NIC and IND–CIN.

  • 32.
    Alomari, Mustafa
    et al.
    UCL School of Pharmacy, University College London.
    Vuddanda, Parameswara Rao
    Luleå University of Technology, Department of Health Sciences, Medical Science. UCL School of Pharmacy, University College London.
    Trenfield, Sarah J.
    UCL School of Pharmacy, University College London.
    Dodoo, Cornelius C.
    UCL School of Pharmacy, University College London.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Basit, Abdul W.
    UCL School of Pharmacy, University College London.
    Gaisford, Simon
    UCL School of Pharmacy, University College London.
    Printing of T3 and T4 Oral Drug Combinations as a Novel Strategy for Hypothyroidism2018In: International Journal of Pharmaceutics, ISSN 0378-5173, E-ISSN 1873-3476, Vol. 549, no 1-2, p. 363-369Article in journal (Refereed)
    Abstract [en]

    Hypothyroidism is a chronic and debilitating disease that is estimated to affect 3% of the general population. Clinical experience has highlighted the synergistic value of combining triiodothyronine (T3) and thyroxine (T4) for persistent or recurrent symptoms. However, thus far a platform that enables the simultaneous and independent dosing of more than one drug for oral administration has not been developed. Thermal inkjet (TIJ) printing is a potential solution to enable the dual deposition of T3 and T4 onto orodispersible films (ODFs) for therapy personalisation. In this study, a two-cartridge TIJ printer was modified such that it could print separate solutions of T3 and T4. Dose adjustments were achieved by printing solutions adjacent to each other, enabling therapeutic T3 (15–50 μg) and T4 dosages (60–180 μg) to be successfully printed. Excellent linearity was observed between the theoretical and measured dose for both T3 and T4 (R2 = 0.982 and 0.985, respectively) by changing the length of the print objective (Y-value). Rapid disintegration of the ODFs was achieved (< 45 seconds). As such, this study for the first time demonstrates the ability to produce personalised dose combinations by TIJ printing T3 and T4 onto the same substrate for oral administration.

  • 33.
    Andersson, Ingalena
    et al.
    Obesity Unit, M73, Huddinge University Hospital.
    Wiklund, Maria Lennernäs
    Swedish Dairy Association, Karolinska Institute.
    Rössner, Stephan
    Obesity Unit, M73, Huddinge University Hospital.
    Meal pattern and risk factor evaluation in one-year completers of a weight reduction program for obese men: The 'Gustaf' study2000In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 247, no 1, p. 30-38Article in journal (Refereed)
    Abstract [en]

    Objectives: To evaluate changes in meal patterns and in obesity related risk factors after 1 year of treatment in obese men. Design: Data from two 24-h dietary recalls, performed at base-line and after 1 year of treatment, were related to changes in medical risk factors. Setting: Academic obesity unit. Subjects: Sixty-three men, aged 44 (eight) years (mean [SD]) and Base- line Body Mass Index (BMI) 37.4 (4.6) kg m-2, who had completed 1 year of treatment. The men were subdivided by tertiles according to weight change: tertile I (n = 21), mean +0.3 kg, tertile II (n = 21), mean -5.8 kg and tertile III (n = 21), mean -14.2 kg. Main outcome measures: Weight loss, changes in meal patterns and in obesity related medical risk factors. Results: The reported mean energy intake decreased after treatment in tertiles II and III by 700 (1300) kcal (P < 0.05) and 700 (900) kcal (P = 0.001), respectively. In tertile III the energy-% from fat decreased (P < 0.05) with a reciprocal increase in energy-% from protein (P < 0.05). The frequency of snacks of a low nutritional quality decreased (P < 0.01) in tertile III together with an increase in energy-% from 'hot meals of good quality' (P < 0.05). Obesity related risk factors (anthropometry, blood pressure, serum lipid concentrations, blood glucose and plasma insulin) improved in a beneficial way only in tertile III. Conclusions: The weight loss in the successful tertile III men was to a great extent explained by fewer low quality snacks but more energy from high quality meals. These changes reflected the behaviour modification strategy recommended.

  • 34.
    Andersson, Mikael
    et al.
    Department of Neuroscience, Physiotherapy, Uppsala University.
    Stridsman, Caroline
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Rönmark, Eva
    National Institute for Working Life, Norrbottens Läns Landsting, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, The OLIN Unit, Umeå University, Karolinska Institutet, Lung and Allergy Research.
    Lindberg, Anne
    Norrbottens Läns Landsting, OLIN studies, Sunderby Hospital, Sunderby sjukhus, Luleå, Department of Public Health and Clinical Medicine, Division of Medicine, Umeå University.
    Emtner, Margareta
    Department of Neuroscience, Physiotherapy, Uppsala University.
    Physical activity and fatigue in chronic obstructive pulmonary disease: A population based study2015In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 109, no 8, p. 1048-1057Article in journal (Refereed)
    Abstract [en]

    Background In subjects with chronic obstructive pulmonary disease (COPD), symptoms of fatigue, concomitant heart disease and low physical activity levels are more frequently described than in subjects without COPD. However, there are no population-based studies addressing the relationship between physical activity, fatigue and heart disease in COPD. The aim was to compare physical activity levels among subjects with and without COPD in a population based study, and to evaluate if concomitant heart disease and fatigue was associated to physical activity. Methods In this, 470 subjects with COPD and 659 subjects without COPD (non-COPD) participated in examinations including structured interview and spirometry. A ratio of the forced expiratory volume in one second (FEV1)/best of forced vital capacity (FVC) and vital capacity (VC) < 0.7 was used to define COPD. Physical activity was assessed with the International Physical Activity Questionnaire (IPAQ), and fatigue with the Functional Assessment of Chronic Illness Therapy - Fatigue scale (FACIT-F). Results The prevalence of low physical activity was higher among subjects with FEV1 < 80% predicted compared to non-COPD subjects (22.4% vs. 14.6%, p=0.041). The factors most strongly associated with low physical activity in subjects with COPD were older age, OR 1.52, (95% CI 1.12 – 2.06), a history of heart disease, OR 2.11 (1.10 - 4.08), and clinically significant fatigue, OR 2.33 (1.31 - 4.13); while obesity was the only significant factor among non-COPD subjects, OR 2.26 (1.17 – 4.35). Conclusion Physical activity levels are reduced when lung function is decreased below 80% of predicted, and the factors associated with low physical activity are different among subject with and without COPD. We propose that the presence of fatigue and heart disease are useful to evaluate when identifying subjects for pulmonary rehabilitation.

  • 35.
    Antzutkin, Oleg
    et al.
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Sustainable Process Engineering.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Wong, Alan
    Physics Department, University of Warwick, Coventry, UK CV4 7AL.
    Dupree, Ray
    Physics Department, University of Warwick, Coventry, UK CV4 7AL.
    Solid-state 17O, 13C and 15N NMR: from tackling structure of Alzheimer's Aβ fibrils to studies on anti-inflammatory drugs, Indomethacin-saccharin cocrystal2007Conference paper (Other academic)
  • 36.
    Ariane, Mostapha
    et al.
    School of Chemical Engineering, University of Birmingham.
    Kassinos, Stavros
    Department of Mechanical and Manufacturing Engineering, University of Cyprus.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Alexiadis, Alessio
    School of Chemical Engineering, University of Birmingham.
    Discrete multi-physics simulations of diffusive and convective mass transfer in boundary layers containing motile cilia in lungs2018In: Computers in Biology and Medicine, ISSN 0010-4825, E-ISSN 1879-0534, Vol. 95, p. 34-42Article in journal (Refereed)
    Abstract [en]

    In this paper, the mass transfer coefficient (permeability) of boundary layers containing motile cilia is investigated by means of discrete multi-physics. The idea is to understand the main mechanisms of mass transport occurring in a ciliated-layer; one specific application being inhaled drugs in the respiratory epithelium. The effect of drug diffusivity, cilia beat frequency and cilia flexibility is studied. Our results show the existence of three mass transfer regimes. A low frequency regime, which we called shielding regime, where the presence of the cilia hinders mass transport; an intermediate frequency regime, which we have called diffusive regime, where diffusion is the controlling mechanism; and a high frequency regime, which we have called convective regime, where the degree of bending of the cilia seems to be the most important factor controlling mass transfer in the ciliated-layer. Since the flexibility of the cilia and the frequency of the beat changes with age and health conditions, the knowledge of these three regimes allows prediction of how mass transfer varies with these factors.

  • 37.
    Backman, Helena
    et al.
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, The OLIN Unit, Umeå University.
    Jansson, Sven-Arne
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN Unit, Umeå University.
    Stridsman, Caroline
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Muellerova, Hana
    Real-World Evidence&Epidemiology, GSK R&D.
    Wurst, Keele
    Real-World Evidence&Epidemiology, GSK R&D.
    Hedman, Linnea
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN Unit, Umeå University.
    Lindberg, Anne
    Department of Public Health and Clinical Medicine, Division of Medicine/the OLIN Unit, Umeå University.
    Rönmark, Eva
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN Unit, Umeå University.
    Chronic airway obstruction in a population-based adult asthma cohort: Prevalence, incidence and prognostic factors2018In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 138, p. 115-122Article in journal (Refereed)
    Abstract [en]

    Background

    Asthma and COPD may overlap (ACO) but information about incidence and risk factors are lacking. This study aimed to estimate prevalence, incidence and risk factors of chronic airway obstruction (CAO) in a population-based adult asthma cohort.

    Methods

    During 1986–2001 a large population-based asthma cohort was identified (n = 2055, 19-72y). Subsamples have participated in clinical follow-ups during the subsequent years. The entire cohort was invited to a clinical follow-up including interview, spirometry, and blood sampling in 2012–2014 when n = 983 subjects performed adequate spirometry. CAO was defined as post-bronchodilator FEV1/FVC<0.7.

    Results

    At study entry, asthmatics with prevalent CAO (11.4%) reported more respiratory symptoms, asthma medication use, and ischemic heart disease than asthmatics without CAO (asthma only). Subjects who developed CAO during follow-up (17.6%; incidence rate of 16/1000/year) had a more rapid FEV1 decline and higher levels of neutrophils than asthma only. Smoking, older age and male sex were independently associated with increased risk for both prevalent and incident CAO, while obesity had a protective effect.

    Conclusions

    In this prospective adult asthma cohort, the majority did not develop CAO. Smoking, older age and male sex were risk factors for prevalent and incident CAO, similar to risk factors described for COPD in the general population.

  • 38.
    Backman, Helena
    et al.
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine, The OLIN Unit, Umeå University.
    Räisänen, Petri
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN unit, Umeå University.
    Hedman, Linnea
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN unit, Umeå University.
    Stridsman, Caroline
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Andersson, Martin
    Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine, The OLIN Unit, Umeå University.
    Lindberg, Anne
    Department of Public Health and Clinical Medicine, Division of Medicine/the OLIN unit, Umeå University.
    Lundbäck, Bo
    Krefting Research Centre, Institute of Medicine, University of Gothenburg.
    Rönmark, Eva
    Department of Public Health and Clinical Medicine, Division of Occupational and Environmental Medicine/the OLIN unit, Umeå University.
    Increased prevalence of allergic asthma from 1996 to 2006 and further to 2016: results from three population surveys2017In: Clinical and Experimental Allergy, ISSN 0954-7894, E-ISSN 1365-2222, Vol. 47, no 11, p. 1426-1435Article in journal (Refereed)
    Abstract [en]

    Background

    During the latter half of the 20th century, the prevalence of asthma and many other allergic diseases has increased. Information on asthma prevalence trends among adults after 2010, especially regarding studies separating allergic asthma from non-allergic asthma, is lacking.

    Objective

    The aim was to estimate prevalence trends of current asthma among adults, both allergic and non-allergic, from 1996 to 2016.

    Methods

    Three cross-sectional samples from the same area of Sweden, 20-69 years, participated in surveys with the same questionnaire in 1996 (n=7104 participants, 85% response rate), 2006 (n=6165, 77%) and 2016 (n=5466, 53%), respectively. Allergic rhino-conjunctivitis (ARC) was used as a marker for allergic sensitization to define allergic asthma.

    Results

    The prevalence of current asthma increased from 8.4% (95% CI: 7.8-9.0) in 1996 to 9.9% (95% CI: 9.2-10.6) in 2006 and 10.9% (95% CI: 10.1-11.7) in 2016 (P<.001). Allergic asthma increased from 5.0% (95% CI: 4.5-5.5) in 1996 to 6.0% (95% CI: 5.4-6.6) in 2006 and further to 7.3% (95% CI: 6.6-8.0) in 2016 (P<.001), while the prevalence of non-allergic asthma remained stable around 3.4%-3.8%. The increase in current asthma was most pronounced among women and among the middle-aged. Physician-diagnosed asthma, asthma medication use and ARC also increased significantly, while the prevalence of symptoms common in asthma such as wheeze and attacks of shortness of breath decreased slightly or was stable. The prevalence of current smoking decreased from 27.4% in 1996 to 12.3% in 2016.

    Conclusions and Clinical Relevance

    The prevalence of allergic asthma increased from 1996 to 2006 and further to 2016, while the prevalence of non-allergic asthma remained on a stable prevalence level. The prevalence of symptoms common in asthma decreased slightly or was stable despite a substantial decrease in the prevalence of current smoking. Clinicians should be aware that the previously observed increase in prevalence of allergic asthma is still ongoing.

  • 39.
    Backman, Ylva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Alerby, Eva
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Bergmark, Ulrika
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Gardelli, Åsa
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Hertting, Krister
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Improvement of school environment from a student perspective: Tensions and opportunities2012In: Education Inquiry, ISSN 2000-4508, E-ISSN 2000-4508, Vol. 3, no 1, p. 19-35Article in journal (Refereed)
    Abstract [en]

    Managerial documents for the national school system in Sweden have emphasised taking students’ voices as a starting point in forming education, and several previous studies have indicated the benefits of giving students opportunities to participate in school. This study aimed to explore students’ reflections on what they would do if they were to decide how to make school the best place for learning. A total of 200 students aged 11 to 15 years from four schools (rural and urban) in two municipalities in the northern part of Sweden participated. The empirical data consisted of the students’ written reflections. The findings fall within four themes: (i) influencing educational settings; (ii) striving for reciprocity; (iii) managing time struggles; and (iv) satisfying well-being needs. Tensions between the students’ previous experiences and future visions appeared. The findings can offer direction regarding aspects of the learning environment in school that could be improved.

  • 40.
    Backman, Ylva
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Alerby, Eva
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Bergmark, Ulrika
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Gardelli, Åsa
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Hertting, Krister
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Öhrling, Kerstin
    Luleå University of Technology, Department of Health Sciences, Nursing Care.
    Learning within and beyond the classroom: compulsory school students voicing their positive experiences of school2012In: Scandinavian Journal of Educational Research, ISSN 0031-3831, E-ISSN 1470-1170, Vol. 56, no 5, p. 555-570Article in journal (Refereed)
    Abstract [en]

    The aim of this study was to describe, reflect upon, and create a deeper understanding of aspects relevant for promoting a positive school environment from a student perspective. The data was analyzed by using an inductive phenomenological method and based on written responses from 200 Swedish students from grades 5–9. The results indicated that the students found aspects within, as well as beyond, the classroom relevant for a positive school environment. For instance, outings were considered relevant for building and maintaining friendships and for learning processes. Moreover, the students discussed formal and informal conditions and considered social as well as structural circumstances important for having a good time in school. The relation between learning and well-being was also emphasized by the students.

  • 41.
    Basavoju, Srinivas
    et al.
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Boström, Dan
    Energy Technology and Thermal Process Chemistry, Umeå University.
    Velaga, Sitaram
    Luleå University of Technology, Department of Health Sciences, Medical Science.
    Pharmaceutical salts of fluoroquinolone antibacterial drugs with acesulfame sweetener2012In: Molecular Crystals and Liquid Crystals, ISSN 1542-1406, E-ISSN 1563-5287, Vol. 562, no 1, p. 254-264Article in journal (Refereed)
    Abstract [en]

    Novel organic salts of norfloxacin and ciprofloxacin with artificial sweeteners such as saccharin and acesulfame were prepared. The two salts 1 and 2 were characterized by differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD). Finally, the crystal structures were solved by single crystal X-ray diffraction data and the structures were analyzed in terms of supramolecular synthons. In norfloxacin acesulfamate 1, two norfloxacin cations and two acesulfame anions form an eight membered cyclic tetramer supramolecular synthon. The salt, ciprofloxacin acesulfamate 2, has a similar structure as salt 1. This study contributes the importance of crystal engineering and supramolecular chemistry to the pharmaceutical applications in terms of interactions and structural correlations in the design of new solid phases. Supplemental materials are available for this article. Go to the publisher's online edition of Molecular Crystals and Liquid Crystals to view the free supplemental file

  • 42.
    Becker, Wulf
    et al.
    National Food Administration, Uppsala.
    Wiklund, Maria Lennernäs
    Department of Medical Sciences, Nutrition, Uppsala University.
    Gustafsson, Inga Britt
    Department of Culinary Art.
    Haraldsdóttir, Johanna
    Research Department of Human Nutrition, Royal Veterinary/Agricultural University, Copenhagen.
    Nydahl, Margaretha C.
    Department of Domestic Sciences, Uppsala University.
    Vessby, Bengt O.H.
    Unit for Clinical Nutrition Research, Department of Public Health Sciences, Uppsala University.
    Ytterfors, Arne
    Unit for Clinical Nutrition Research, Department of Public Health Sciences, Uppsala University.
    Precoded food records compared with weighed food records for measuring dietary habits in a population of Swedish adults1998In: Scandinavian Journal of Nutrition/Næringsforskning, ISSN 1102-6480, E-ISSN 1651-2359, Vol. 42, no 4, p. 145-149Article in journal (Refereed)
    Abstract [en]

    In a cross-over design, 82 women and men recorded their food intake by a precoded 7-day record book (PR) including both standard portions in household measures and photographs, and a weighed 7-day record (WR), respectively. Single 24-h urine samples, for determination of nitrogen excretion, were collected for 39 subjects during the WR period. Comparing the PR to the WR method, the mean intake of some foods, as cheese, was higher, and bread and vegetables lower. For energy and nutrients, the fat energy percent (E%) was higher, and protein E%, dietary fibre, iron, thiamin, folate, carotene and α-tocopherol were all lower. Protein intake registered by the PR method was 20% lower compared to 24-h urine samples, and 11% lower for the WR method. The results indicate that some of the standard portion sizes, used by the PR method, contributed to the observed differences in food and nutrient intakes. The subjects found it easier and less time-consuming to record their food intake with the PR than with the WR method. The time spent on processing data was reduced by 50% when using the PR method. The results of the study will be used for improvements in the design of the PR for use in large-scale dietary surveys for monitoring dietary habits.

  • 43.
    Bejarano, J.
    et al.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Navarro-Marquez, M.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Morales-Zavala, F.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Morales, Javier O.
    Luleå University of Technology, Department of Health Sciences, Medical Science. Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Departamento de Ciencias y Tecnología Farmacéuticas, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile.
    Garcia-Carvajal, I.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Araya-Fuentes, E.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Departamento de Ciencias Quimicas, Facultad de Ciencias Exactas, Universidad Andres Bello, Santiago, Chile.
    Flores, Y.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile.
    Verdejo, H.E.
    Advanced Center for Chronic Diseases (ACCDiS), División de Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Castro, P.F.
    Advanced Center for Chronic Diseases (ACCDiS), División de Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
    Lavandero, S.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios en Ejercicio, Metabolismo y Cáncer (CEMC), Instituto de Ciencias Biomedicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile; Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, TX, United States.
    Kogan, M.J.
    Advanced Center for Chronic Diseases (ACCDiS), Facultad Ciencias Químicas y Farmaceuticas, Universidad de Chile, Santiago, Chile; Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Chile.
    Nanoparticles for diagnosis and therapy of atherosclerosis and myocardial infarction: evolution toward prospective theranostic approaches2018In: Theranostics, ISSN 1838-7640, E-ISSN 1838-7640, no 17, p. 4710-4732Article in journal (Refereed)
    Abstract [en]

    Cardiovascular diseases are the leading cause of death worldwide. Despite preventive efforts, early detection of atherosclerosis, the common pathophysiological mechanism underlying cardiovascular diseases remains elusive, and overt coronary artery disease or myocardial infarction is often the first clinical manifestation. Nanoparticles represent a novel strategy for prevention, diagnosis, and treatment of atherosclerosis, and new multifunctional nanoparticles with combined diagnostic and therapeutic capacities hold the promise for theranostic approaches to this disease. This review focuses on the development of nanosystems for therapy and diagnosis of subclinical atherosclerosis, coronary artery disease, and myocardial infarction and the evolution of nanosystems as theranostic tools. We also discuss the use of nanoparticles in noninvasive imaging, targeted drug delivery, photothermal therapies together with the challenges faced by nanosystems during clinical translation.

  • 44.
    Berglund, Lotta
    et al.
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Tossavainen, Mia
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Nilsson, Kristina L.
    Luleå University of Technology, Department of Civil, Environmental and Natural Resources Engineering, Architecture and Water.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Health on thin ice: methods of giving voice to Swedish citizens in urban planning and design to promote health in a cold climate2013Conference paper (Other academic)
    Abstract [en]

    In the northern, sub-arctic, regions of the world the climate is cold a substantial part of the year which affecting people's health as low temperatures and darkness stress the body. At the same time the cold climate offers opportunities that can be utilized in an innovative manner, both technically and aesthetically, to develop the winter environment to be attractive and health promoting in outdoor activities.The aim of the study was to develop a methodology for giving voice to citizens to be used in the process of urban planning and design for good health in a cold climate. The qualitative investigations of citizen’s experiences of health promoting aspects included two workshops focused on the following questions; What are your experiences of health and well-being in a cold climate? How can this city be planned to promote health during the winter season? The 53 participants came from two cities in the northern part of Sweden. At Workshop 1 small groups of citizens (5-8) were asked to make a collective collage cutting and pasting images from magazines without talking to each other while soft music was playing in the background.When finished the silence was broken and the participants presented their contributions. At Workshop 2 small groups of citizens (5-8) were given maps of the city with different paths for walking tours aimed to pinpoint areas for improvement. After the walk the group presented their ideas for each other and a number of innovative ideas surfaced.Including citizens in the process of urban planning is not only a good source of ideas and information useful in the planning process but may be an opportunity to strengthen health literacy and healthy behavior. This study may serve as an example of an empowerment - based method including citizens in the process of urban planning and design.

  • 45.
    Bergmark, Ulrika
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Appreciation as fuel for school improvement2011Conference paper (Other academic)
  • 46.
    Bergmark, Ulrika
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Appreciative based learning and research: amplifying the positive2009Conference paper (Other academic)
    Abstract [en]

    In this paper we will explore and discuss possibilities to learn and research through an appreciative approach in order to enhance continuing professional development for teachers and leaders in school systems. Traditionally humans are used to define problems and trying to find solutions. This involves identification of the bad or threatening and preventing it from taking place, in other words prevention. What would happen if we choose to solve problems in a different way: identify what we appreciate and let this be the base for continued development and improvement? A promoting perspective and salutogenic focus has shown to be successful in helping humans increase their experience of health, which may also create opportunities for learning. How would it be if we changed our point of departure in learning and research processes from problems to appreciation?Our thoughts about Appreciative Based Learning (ABL) has evolved while working with Problem Based Learning (PBL) as teachers. When we came in contact with Participatory and Appreciative Action Research (PAAR) and Appreciative Inquiry we sensed an increased opportunity for positive change, a new way of working with education and research. PAAR can be seen both as a process of building and sustaining change in organizations (Participation, Appreciation, Action and Reflection) and also as a research methodology. PAAR has its roots in action research which is a problem based method aiming at developing and improving practice. Action research can be seen as participatory and collaborative research. A central question in this kind of research is how change of practice can be done, individually or collectively. The new aspect in PAAR is appreciation. An improvement process starts from for example acknowledging factors that work well in an organization or for an individual and the next step is to amplify these positive factors. PAAR research seeks for example to explore positive experiences of a phenomenon and how these experiences can be amplified and sustained in a practice.Central aspects of ABL are appreciation, participation, multimodalities, learning from each other and reflection. Just like PAAR, ABL can offer an opportunity to take positive questions and turn them into positive actions. We will give examples of how we as teachers and researchers have applied ABL in our own teaching and research. Finally we raise questions of how ABL can play a role in school improvement and educational research, building not only a better school but a better future as well.Methodology or methods/research instruments or sources used:We will focus on how to use ABL in the field of school improvement generally and specifically pertaining to educational research, through giving the theoretical background and examples of how we have applied ABL. We have been inspired by ABL in our own research, when teaching in higher education and when working with continuing professional development for teachers and leaders in school systems.Conclusions or expected outcomes or findings:This paper seeks to introduce and explore ABL as a method in school improvement processes and in educational research. We will share our process in developing ABL; how we have applied ABL in our teaching and research. We hope that our thoughts about the possibility to learn and research through an appreciative approach will inspire the participants to reflect on their own practice.

  • 47.
    Bergmark, Ulrika
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Creating opportunities for diversity and unpredictability: inviting children to be co-researchers2014Conference paper (Refereed)
  • 48.
    Bergmark, Ulrika
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Leadership for learning and well-being with an appreciative attitude2011Conference paper (Other academic)
  • 49.
    Bergmark, Ulrika
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Let’s have a “school-rules-attitude”2015In: Empowering School eHealth Model in the Barents Region, Rovaniemi: Lapland University of Applied Sciences. , 2015, p. 309-311Chapter in book (Refereed)
  • 50.
    Bergmark, Ulrika
    et al.
    Luleå University of Technology, Department of Arts, Communication and Education, Education, Language, and Teaching.
    Kostenius, Catrine
    Luleå University of Technology, Department of Health Sciences, Health and Rehab.
    Listen to me when I have something to say: students paricipation in research for sustainable school improvement2009In: Improving Schools, ISSN 1365-4802, E-ISSN 1475-7583, Vol. 12, no 3, p. 249-260Article in journal (Refereed)
    Abstract [en]

    This article focuses on student participation in the research process as a contribution to school improvement. The specific aim of this article was to explore students' participation in different phases of a research process and discuss how their participation can contribute to school improvement. Based on a life-world phenomenological ontology, we used two research and development projects - Full of Value and Arctic Children - to shed light on participation in research. When doing research together with students, we have been inspired by Participatory Appreciative Action Research (PAAR). The methods used in the projects were open writing, group reflection, drawings, and exhibition discussions. This research showed that students were able to explore and express their lived experiences of behaviour and well-being in school, and how this was linked to positive change. We found students trustworthy, capable, and competent, enriching the process of school improvement.

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