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  • 51.
    Alvebratt, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Petersson, Erik
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Physics.
    Bergström, Christel
    A small scale method to determine release rate from complex carrier-mediated systems2016In: Emerging Technologies in Drug Discovery and Development. Zhuhai, August 23-26, 2016., 2016Conference paper (Refereed)
  • 52.
    Alvebratt, Caroline
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Strömme, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Bergström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    A new method that enables in situ measurement of drug release from complex carrier-mediated systems2017In: 6th FIP Pharmaceutical Sciences World Congress2017., 2017Conference paper (Refereed)
  • 53.
    Alzghoul, Ahmad
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computing Science.
    Alhalaweh, Amjad
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Mahlin, Denny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, Christel A. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Experimental and Computational Prediction of Glass Transition Temperature of Drugs2014In: JOURNAL OF CHEMICAL INFORMATION AND MODELING, ISSN 1549-9596, Vol. 54, no 12, p. 3396-3403Article in journal (Refereed)
    Abstract [en]

    Glass transition temperature (T-g) is an important inherent property of an amorphous solid material which is usually determined experimentally. In this study, the relation between T-g and melting temperature (T-m) was evaluated using a data set of 71 structurally diverse druglike compounds. Further, in silico models for prediction of T-g were developed based on calculated molecular descriptors and linear (multilinear regression, partial least-squares, principal component regression) and nonlinear (neural network, support vector regression) modeling techniques. The models based on T-m predicted T-g with an RMSE of 19.5 K for the test set. Among the five computational models developed herein the support vector regression gave the best result with RMSE of 18.7 K for the test set using only four chemical descriptors. Hence, two different models that predict T-g of drug-like molecules with high accuracy were developed. If T-m is available, a simple linear regression can be used to predict T-g. However, the results also suggest that support vector regression and calculated molecular descriptors can predict T-g with equal accuracy, already before compound synthesis.

  • 54. AMIDON, GL
    et al.
    LENNERNAS, H
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    SHAH, VP
    CRISON, JR
    A THEORETICAL BASIS FOR A BIOPHARMACEUTIC DRUG CLASSIFICATION - THE CORRELATION OF IN-VITRO DRUG PRODUCT DISSOLUTION AND IN-VIVO BIOAVAILABILITY1995In: PHARMACEUTICAL RESEARCH, Vol. 12, p. 413-Article in journal (Refereed)
  • 55.
    Amidon, Gregory E.
    et al.
    Univ Michigan, Ann Arbor, MI USA.
    Anderson, Bradley D.
    Univ Kentucky, Lexington, KY 40506 USA.
    Balthasar, Joseph P.
    SUNY Buffalo, Univ Buffalo, Buffalo, NY USA.
    Bergström, Christel A.S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Huang, Shiew-Mei
    US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
    Kasting, Gerald
    Univ Cincinnati, Cincinnati, OH USA.
    Kesisoglou, Filippos
    Merck & Co Inc, Kenilworth, NJ USA.
    Khinast, Johannes G.
    Graz Univ Technol, Inst Proc & Particle Engn, Graz, Austria.
    Mager, Donald E.
    SUNY Buffalo, Univ Buffalo, Buffalo, NY USA.
    Roberts, Christopher J.
    Univ Delaware, Newark, DE USA.
    Yu, Lian
    Univ Wisconsin, Madison, WI USA.
    Fifty-Eight Years and Counting: High-Impact Publishing in Computational Pharmaceutical Sciences and Mechanism-Based Modeling2019In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 108, no 1, p. 2-7Article in journal (Refereed)
    Abstract [en]

    With this issue of the Journal of Pharmaceutical Sciences, we celebrate the nearly 6 decades of contributions to mechanistic-based modeling and computational pharmaceutical sciences. Along with its predecessor, The Journal of the American Pharmaceutical Association: Scientific Edition first published in 1911, JPharmSci has been a leader in the advancement of pharmaceutical sciences beginning with its inaugural edition in 1961. As one of the first scientific journals focusing on pharmaceutical sciences, JPharmSci has established a reputation for publishing high-quality research articles using computational methods and mechanism-based modeling. The journal’s publication record is remarkable. With over 15,000 articles, 3000 notes, and more than 650 reviews from industry, academia, and regulatory agencies around the world, JPharmSci has truly been the leader in advancing pharmaceutical sciences.

  • 56. Amidon, K. S.
    et al.
    Langguth, P.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Yu, L.
    Amidon, G. L.
    Bioequivalence of Oral Products and the Biopharmaceutics Classification System: Science, Regulation, and Public Policy2011In: Clinical Pharmacology and Therapeutics, ISSN 0009-9236, E-ISSN 1532-6535, Vol. 90, no 3, p. 467-470Article in journal (Refereed)
    Abstract [en]

    The demonstration of bioequivalence (BE) is an essential requirement for ensuring that patients receive a product that performs as indicated by the label. The BE standard for a particular product is set by its innovator, and this standard must subsequently be matched by generic drug products. The Biopharmaceutics Classification System (BCS) sets a scientific basis for an improved BE standard for immediate-release solid oral dosage forms. In this paper, we discuss BE and the BCS, as well as the issues that are currently relevant to BE as a pharmaceutical product standard.

  • 57.
    Amini, A
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Merclin, N
    Department of Pharmacy.
    Bastami, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Westerlund, D
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
    Determination of association constants between enantiomers of orciprenaline and methyl-beta-cyclodextrin as chiral selector by capillary zone electrophoresis using a partial filling technique1999In: ELECTROPHORESIS, Vol. 20, p. 180-Article in journal (Refereed)
  • 58. Amini, Ahmad
    et al.
    Merclin, Nadia
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Bastami, Salumeh
    Westerlund, Douglas
    Determination of association constants between enantiomers of orciprenaline and methyl-β-cyclodextrin as chiral selector by capillary zone electrophoresis using a partial filling technique1999In: Electrophoresis, Vol. 20, p. 180-188Article in journal (Refereed)
  • 59.
    Andersson, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Konkreta förbättringsförslag på farmaceutisk produktion för minimering av skadat innehåll av Salazopyrin EN-tabs 500mg2013Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 60.
    Andersson, Kristin
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Melander, Arne
    Svensson, Carin
    Lind, Owe
    Nilsson, J. Lars G.
    Repeat prescriptions: refill adherence in relation to patient and prescriber characteristics, reimbursement level and type of medication2005In: Eur J Public Health, ISSN 1101-1262, Vol. 15, no 6, p. 621-626Article in journal (Refereed)
  • 61.
    Andersson, Margaretha
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Surface Biotechnology. Department of Physical and Analytical Chemistry, Surface Biotechnology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry.
    Fromell, Karin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Surface Biotechnology. Department of Physical and Analytical Chemistry, Surface Biotechnology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry.
    Gullberg, Elisabet
    Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy. Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Artursson, Per
    Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy. Department of Physical and Analytical Chemistry, Surface Biotechnology.
    Caldwell, Karin
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Surface Biotechnology. Department of Physical and Analytical Chemistry, Surface Biotechnology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry.
    Characterization of Surface-Modified Nanoparticles for in Vivo Biointeraction. A Sedimentation Field Flow Fractionation Study2005In: Analytical Chemistry, Vol. 77, p. 5488-5493Article in journal (Refereed)
    Abstract [en]

    Sedimentation field flow fractionation (SdFFF) is an emerging high-performance analytical tool for separation and determination of size and adsorption characteristics of colloidal particles. This study demonstrates how SdFFF can be used to characterize nanoparticles prepared for in vivo applications including (1) the quantification of polymer uptake on nanoparticles where surface coverage is crucial and (2) the coupling of cell adhesive peptides containing the Arg-Gly-Asp motif (RGD). Quantitative information about polymer adhesion in order to prepare a bioinert surface and an accurate determination of ligand uptake are both of obvious importance for the understanding of, for example, relations between the number of attached molecules for biointeraction and an observed therapeutic effect. In addition, the present work highlights the necessity to perform careful characterization of commercially available particulate starting materials, in terms of size and polydispersity, prior to biological experimentation.

  • 62.
    Andersson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Brittebo, Eva B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Correction: Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id e78133Article in journal (Refereed)
  • 63.
    Andersson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humansManuscript (preprint) (Other academic)
  • 64.
    Andersson, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Phase Phenomena in Polymer Networks: Empirical Studies on the Influence of Hydrophobicity, Charge Density and Crosslinks on Macroion-Induced Phase Transitions in Polyelectrolyte Gels2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The thesis concerns polyelectrolyte gels in contact with oppositely charged proteins and surfactant micelles, and includes of four papers (I-IV). In paper I confocal Raman spectroscopy was introduced as a method to trace micelles and investigate the structure of gel-surfactant complexes, in phase separated gel spheres. In paper II, the binding of surfactants to microspheres (~50-100 µm) was investigated by means of a micromanipulator-assisted microscopy method. The two surfactants were found to display qualitative difference respect to degree of swelling, surfactant distribution in the gels, and the difference is discussed in terms of absence/presence of hydrophobic attraction to the polyelectrolyte gel network. Kinetics of volume change in gels were analyzed. Aggregation numbers of micelles in polystyrenesulfonate (PSS) solutions, obtained from fluorescence quenching measurements, are presented. In paper III, phase behaviour, protein assembly and diffusion, was studied in PSS gel microspheres. Interpretation of results was aided by measurements of osmotic swelling of individual gel networks, and by combining the results with studies of protein diffusion in macroscopic (cm-sized) gel spheres. Complexes formed were further analyzed with small angle x-ray spectroscopy. In paper IV phase behaviour of mixed ionic/nonionic surfactant micelles is investigated in cm-sized gel spheres. The coexistence of three phases, the formation of dense shells in the bulk of the gels and other phenomena are described for the first time, and the results are presented along with discussion on the charge-density of spherical micelles and of  network induced hysteresis effects in gels. The composition and microstructure of phases are investigated by confocal Raman spectroscopy and small-angle x-ray scattering respectively. The results are interpreted with aid of highly detailed theoretical model calculations.

    List of papers
    1. Differences in binding of a cationic surfactant to cross-linked sodium poly(acrylate) and sodium poly(styrene sulfonate) studied by Raman spectroscopy
    Open this publication in new window or tab >>Differences in binding of a cationic surfactant to cross-linked sodium poly(acrylate) and sodium poly(styrene sulfonate) studied by Raman spectroscopy
    2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 7, p. 2761-2765Article in journal (Refereed) Published
    Abstract [en]

    Raman spectroscopy has been used to investigate the structure of gel-surfactant complexes. Cross-linked sodium poly(acrylate) and sodium poly(styrene sulfonate) were immersed in solutions of the cationic surfactant dodecyl trimethylammonium bromide. During the deswelling process, two distinct regions could be observed for both types of gels. Looking at the Raman spectra, however, for the poly(styrene sulfonate), the surfactant could be found throughout the gel particle, whereas for poly(acrylate), essentially all the surfactant was bound in a surface layer.

    National Category
    Inorganic Chemistry
    Research subject
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-70227 (URN)10.1021/la0468693 (DOI)15779946 (PubMedID)
    Available from: 2008-12-16 Created: 2008-12-16 Last updated: 2017-11-21
    2. Single microgel particle studies demonstrate the influence of hydrophobic interactions between charged micelles and oppositely charged polyions.
    Open this publication in new window or tab >>Single microgel particle studies demonstrate the influence of hydrophobic interactions between charged micelles and oppositely charged polyions.
    2005 (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 9, p. 3773-3781Article in journal (Refereed) Published
    Abstract [en]

    The binding of two cationic surfactants, dodecyltrimethylammonium bromide (DoTAB) and N-(1,1,2,2-tetrahydroperfluorodecanyl)pyridinium bromide (HFDePB), to covalently cross-linked sodium poly(styrenesulfonate) (PSS) microgels has been investigated by means of micromanipulator-assisted time-resolved light microscopy on single gels. It is demonstrated that repeated measurements on the same microgel under conditions of controlled liquid flow give highly reproducible results. The two surfactants are found to behave very differently with respect to degree of swelling, surfactant distribution in the gels, both during shrinking and at equilibrium, and kinetics of volume changes induced by them. The main difference is attributed to the presence of a hydrophobic interaction between PSS and the DoTAB micelles, absent in the case of HFDePB. Kinetic shrinking curves are recorded and analyzed using a model for steady-state transport of surfactant between the solution and the gels. Aggregation numbers for DoTAB in PSS solutions obtained from fluorescence quenching measurements are presented. A strong dependence on the surfactant-to-polyion concentration ratio is observed. Relations between surfactant binding isotherms, phase diagrams for linear polyelectrolyte/surfactant/water systems, and the binding to gels are discussed.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-92344 (URN)10.1021/la047316v (DOI)15835936 (PubMedID)
    Available from: 2004-10-29 Created: 2004-10-29 Last updated: 2017-12-14Bibliographically approved
    3. Lysozyme Incorporation in Poly(styrenesulfonate) Microspheres: Dynamics of Core/Shell formation
    Open this publication in new window or tab >>Lysozyme Incorporation in Poly(styrenesulfonate) Microspheres: Dynamics of Core/Shell formation
    (English)Manuscript (preprint) (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-145378 (URN)
    Available from: 2011-02-08 Created: 2011-02-08 Last updated: 2011-02-24
    4. Mixed Micelles in Spherical Polyelectrolyte Networks: Influence of Crosslinks on Charge Induced Phase Separation
    Open this publication in new window or tab >>Mixed Micelles in Spherical Polyelectrolyte Networks: Influence of Crosslinks on Charge Induced Phase Separation
    (English)Manuscript (preprint) (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-145379 (URN)
    Available from: 2011-02-08 Created: 2011-02-08 Last updated: 2011-02-24
  • 65.
    Andersson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Binding of Lysozyme to Spherical Poly(styrenesulfonate) Gels2018In: Gels, ISSN 2084-1469, E-ISSN 1808-1878, Vol. 4, no 1, article id 9Article in journal (Refereed)
    Abstract [en]

    Polyelectrolyte gels are useful as carriers of proteins and other biomacromolecules in, e.g., drug delivery. The rational design of such systems requires knowledge about how the binding and release are affected by electrostatic and hydrophobic interactions between the components. To this end we have investigated the uptake of lysozyme by weakly crosslinked spherical poly(styrenesulfonate) (PSS) microgels and macrogels by means of micromanipulator assisted light microscopy and small angle X-ray scattering (SAXS) in an aqueous environment. The results show that the binding process is an order of magnitude slower than for cytochrome c and for lysozyme binding to sodium polyacrylate gels under the same conditions. This is attributed to the formation of very dense protein-rich shells in the outer layers of the microgels with low permeability to the protein. The shells in macrogels contain 60 wt % water and nearly charge stoichiometric amounts of lysozyme and PSS in the form of dense complexes of radius 8 nm comprising 30–60 lysozyme molecules. With support from kinetic modelling results we propose that the rate of protein binding and the relaxation rate of the microgel are controlled by the protein mass transport through the shell, which is strongly affected by hydrophobic and electrostatic interactions. The mechanism explains, in turn, an observed dependence of the diffusion rate on the apparent degree of crosslinking of the networks.

  • 66.
    Andersson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Hansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Phase Behavior of Salt-Free Polyelectrolyte Gel-Surfactant Systems2017In: Journal of Physical Chemistry B, ISSN 1520-6106, E-ISSN 1520-5207, Vol. 121, no 24, p. 6064-6080Article in journal (Refereed)
    Abstract [en]

    Ionic surfactants tend to collapse the outer parts of polyelectrolyte gels, forming shells that can be used to encapsulate other species including protein and peptide drugs. In this paper, the aqueous phase behavior of covalently cross-linked polyacrylate networks containing sodium ions and dodecyltrimethylammonium ions as counterions is investigated by means of swelling isotherms, dye staining, small-angle X-ray scattering, and confocal Raman spectroscopy. The equilibrium state is approached by letting the networks absorb pure water. With an increasing fraction of surfactant ions, the state of the water-saturated gels is found to change from being swollen and monophasic, via multiphasic states, to collapsed and monophasic. The multiphasic gels have a swollen, micelle-lean core surrounded by a collapsed, micelle- rich shell, or a collapsed phase forming a spheroidal inner shell separating two micelle-lean parts. It is shown that the transition between monophasic and core-shell states can be induced by variation of the osmotic pressure and variation of the charge of the micelles by forming mixed micelles with the nonionic surfactant octaethyleneglycol monododecylether. The experimental data are compared with theoretical predictions of a model derived earlier. In the calculations, the collapsed shell is assumed to be homogeneous, an approximation introduced here and shown to be excellent for a wide range of compositions. The theoretical results highlight the electrostatic and hydrophobic driving forces behind phase separation.

  • 67.
    Andersson, Martin
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Råsmark, Per Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical Chemistry.
    Elvingson, Christer
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Hansson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Single microgel particle studies demonstrate the influence of hydrophobic interactions between charged micelles and oppositely charged polyions.2005In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827, Vol. 21, no 9, p. 3773-3781Article in journal (Refereed)
    Abstract [en]

    The binding of two cationic surfactants, dodecyltrimethylammonium bromide (DoTAB) and N-(1,1,2,2-tetrahydroperfluorodecanyl)pyridinium bromide (HFDePB), to covalently cross-linked sodium poly(styrenesulfonate) (PSS) microgels has been investigated by means of micromanipulator-assisted time-resolved light microscopy on single gels. It is demonstrated that repeated measurements on the same microgel under conditions of controlled liquid flow give highly reproducible results. The two surfactants are found to behave very differently with respect to degree of swelling, surfactant distribution in the gels, both during shrinking and at equilibrium, and kinetics of volume changes induced by them. The main difference is attributed to the presence of a hydrophobic interaction between PSS and the DoTAB micelles, absent in the case of HFDePB. Kinetic shrinking curves are recorded and analyzed using a model for steady-state transport of surfactant between the solution and the gels. Aggregation numbers for DoTAB in PSS solutions obtained from fluorescence quenching measurements are presented. A strong dependence on the surfactant-to-polyion concentration ratio is observed. Relations between surfactant binding isotherms, phase diagrams for linear polyelectrolyte/surfactant/water systems, and the binding to gels are discussed.

  • 68.
    Andersson, Sara B. E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alvebratt, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Controlled Suspensions Enable Rapid Determinations of Intrinsic Dissolution Rate and Apparent Solubility of Poorly Water-Soluble Compounds2017In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 34, no 9, p. 1805-1816Article in journal (Refereed)
    Abstract [en]

    Purpose: To develop a small-scale set-up to rapidly and accurately determine the intrinsic dissolution rate (IDR) and apparent solubility of poorly water-soluble compounds.

    Methods: The IDR and apparent solubility (S-app) were measured in fasted state simulated intestinal fluid (FaSSIF) for six model compounds using wet-milled controlled suspensions (1.0% (w/w) PVP and 0.2% (w/w) SDS) and the mu DISS Profiler. Particle size distribution was measured using a Zetasizer and the total surface area was calculated making use of the density of the compound. Powder and disc dissolution were performed and compared to the IDR of the controlled suspensions.

    Results: The IDR values obtained from the controlled suspensions were in excellent agreement with IDR from disc measurements. The method used low amount of compound (mu g-scale) and the experiments were completed within a few minutes. The IDR values ranged from 0.2-70.6 mu g/min/cm(2) and the IDR/S-app ratio ranged from 0.015 to 0.23. This ratio was used to indicate particle size sensitivity on intestinal concentrations reached for poorly water-soluble compounds.

    Conclusions: The established method is a new, desirable tool that provides the means for rapid and highly accurate measurements of the IDR and apparent solubility in biorelevant dissolution media. The IDR/S-app is proposed as a measure of particle size sensitivity when significant solubilization may occur.

  • 69.
    Andersson, Sara B. E.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Alvebratt, Caroline
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bevernage, Jan
    Janssen Pharmaceut, Pharmaceut Sci, B-2340 Beerse, Belgium.
    Bonneau, Damien
    Sanofi Aventis Rech Dev, Chem & Pharmaceut Anal, F-34184 Montpellier, France.
    da Costa Mathews, Claudia
    Pfizer Ltd, Pharmaceut Sci, Drug Product Design, Sandwich CT13 9NJ, Kent, England.
    Dattani, Rikesh
    AstraZeneca, Prod Dev, Biopharmaceut, Macclesfield SK10 2NA, Cheshire, England.
    Edueng, Khadijah
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    He, Yan
    Sanofi, Predev Sci, Waltham, MA 02451 USA.
    Holm, René
    Pharmaceut Sci & CMC Biol, DK-2500 Copenhagen, Denmark; Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2100 Copenhagen, Denmark.
    Madsen, Cecilie
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2100 Copenhagen, Denmark.
    Müller, Thomas
    AbbVie Deutschland GmbH & Co KG, Drug Prod Dev, D-67061 Ludwigshafen, Germany.
    Muenster, Uwe
    Bayer Pharma AG, Res Ctr Aprath, Chem & Pharmaceut Dev, D-42096 Wuppertal, Germany.
    Müllertz, Anette
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2100 Copenhagen, Denmark.
    Ojala, Krista
    Orion Pharma, POB 65, Espoo 02101, Finland.
    Rades, Thomas
    Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2100 Copenhagen, Denmark.
    Sieger, Peter
    Boehringer Ingelheim GmbH & Co KG, Pharmaceut Dev, D-55218 Ingelheim, Germany.
    Bergström, Christel A. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Interlaboratory Validation of Small-Scale Solubility and Dissolution Measurements of Poorly Water-Soluble Drugs2016In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 105, no 9, p. 2864-2872Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to investigate the interlaboratory variability in determination of apparent solubility (Sapp) and intrinsic dissolution rate (IDR) using a miniaturized dissolution instrument. Three poorly water-soluble compounds were selected as reference compounds and measured at multiple laboratories using the same experimental protocol. Dissolution was studied in fasted-state simulated intestinal fluid and phosphate buffer (pH 6.5). An additional 6 compounds were used for the development of an IDR measurement guide, which was then validated with 5 compounds. The results clearly showed a need for a standardized protocol including both the experimental assay and the data analysis. Standardization at both these levels decreased the interlaboratory variability. The results also illustrated the difficulties in performing disc IDR on poorly water-soluble drugs because the concentrations reached are typically below the limit of detection. The following guidelines were established: for compounds with Sapp > 1 mg/mL, the disc method is recommended. For compounds with Sapp <100 μg/mL, IDR is recommended to be performed using powder dissolution. Compounds in the interval 100 μg/mL to 1 mg/mL can be analyzed with either of these methods.

  • 70. Antonescu, Irina E
    et al.
    Rasmussen, Karina F
    Neuhoff, Sibylle
    Fretté, Xavier
    Karlgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, Christel A. S.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Nielsen, Carsten Uhd
    Steffansen, Bente
    The Permeation of Acamprosate Is Predominantly Caused by Paracellular Diffusion across Caco-2 Cell Monolayers: A Paracellular Modeling Approach.2019In: Molecular Pharmaceutics, ISSN 1543-8384, E-ISSN 1543-8392Article in journal (Refereed)
    Abstract [en]

    In drug development, estimating fraction absorbed (Fa) in man for permeability-limited compounds is important but challenging. To model Fa of such compounds from apparent permeabilities (Papp) across filter-grown Caco-2 cell monolayers, it is central to elucidate the intestinal permeation mechanism(s) of the compound. The present study aims to refine a computational permeability model to investigate the relative contribution of paracellular and transcellular routes to the Papp across Caco-2 monolayers of the permeability-limited compound acamprosate having a bioavailability of ∼11%. The Papp values of acamprosate and of several paracellular marker molecules were measured. These Papp values were used to refine system-specific parameters of the Caco-2 monolayers, that is, paracellular pore radius, pore capacity, and potential drop. The refined parameters were subsequently used as an input in modeling the permeability (Pmodeled) of the tested compounds using mathematical models collected from two published permeability models. The experimental data show that acamprosate Papp across Caco-2 monolayers is low and similar in both transport directions. The obtained acamprosate Papp, 1.56 ± 0.28 × 10-7 cm·s-1, is similar to the Papp of molecular markers for paracellular permeability, namely, mannitol (2.72 ± 0.24 × 10-7 cm·s-1), lucifer yellow (1.80 ± 0.35 × 10-7 cm·s-1), and fluorescein (2.10 ± 0.28 × 10-7 cm·s-1), and lower than that of atenolol (7.32 ± 0.60 × 10-7 cm·s-1; mean ± SEM, n = 3-6), while the end-point amount of acamprosate internalized by the cell monolayer, Qmonolayer, was lower than that of mannitol. Acamprosate did not influence the barrier function of the monolayers since it altered neither the Papp of the three paracellular markers nor the transepithelial electrical resistance (TEER) of the cell monolayer. The Pmodeled for all the paracellular markers and acamprosate was dominated by the Ppara component and matched the experimentally obtained Papp. Furthermore, acamprosate did not inhibit the uptake of probe substrates for solute carriers PEPT1, TAUT, PAT1, EAAT1, B0,+AT/rBAT, OATP2B1, and ASBT expressed in Caco-2 cells. Thus, the Pmodeled estimated well Ppara, and the paracellular route appears to be the predominant mechanism for acamprosate Papp across Caco-2 monolayers, while the alternative transcellular routes, mediated by passive diffusion or carriers, are suggested to only play insignificant roles.

  • 71.
    Antonov, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    antonov, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Isacson, Dag
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Prescription and non-prescription analgesics in Sweden.1998In: Ann Pharmacotherapy, Vol. 32, p. 485-Article in journal (Refereed)
  • 72.
    Antonov, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Isacson, D
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Use of analgesic drugs in Sweden - the importance of sociodemographic factors, physical fitness, health and healthrelated factors and working conditions1996In: Social Science and Medicine, Vol. 42, p. 1473-Article in journal (Refereed)
  • 73.
    Antonov, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Isacson, Dag
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Headace and analgesic use in Sweden.1998In: Headace, Vol. 38, p. 97-Article in journal (Refereed)
  • 74.
    Antonov, K
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Isacson, Dag
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Headache in Sweden - The importance of working conditions.1997In: Headache, Vol. 37, p. 228-Article in journal (Refereed)
  • 75.
    Appel, Lieuwe
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Section of Nuclear Medicine and PET.
    Bergström, Mats
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lassen, Jorgen Buus
    Långström, Bengt
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - BMC, Physical Organic Chemistry.
    Tesofensine, a novel triple monoamine re-uptake inhibitor with anti-obesity effects: Dopamine transporter occupancy as measured by PET2014In: European Neuropsychopharmacology, ISSN 0924-977X, E-ISSN 1873-7862, Vol. 24, no 2, p. 251-261Article in journal (Refereed)
    Abstract [en]

    Tesofensine (TE) is a novel triple monoannine re-uptake inhibitor inducing a potent inhibition of the re-uptake process in the synaptic cleft of the neurotransmitters dopamine, norepinephrine, and serotonin. In recent preclinical and clinical evaluations TE showed a robust anti-obesity effect, but the specific mechanism of this triple monoamine re-uptake inhibitor still needs to be further elucidated. This positron emission tomography (PET) study, using [C-11]beta CIT-FE, aimed to assess the degree of the dopamine transporter (DAT) occupancy, at constant TE plasma levels, following different oral, multiple doses of TE during totally 8-12 days. In addition, the relationships between DAT occupancy and TE plasma concentrations, or doses, were investigated to enable assessment of DAT occupancies in subsequent clinical trials. The results demonstrated that TE induced a dose-dependent blockade of DAT following multiple doses of 0.125-1 mg TE at anticipated steady-state conditions. The mean striatal DAT occupancy varied dose-dependently between 18% and 77%. A signnoid E-max model well described the relationship between striatal DAT occupancy and TE plasma concentrations or doses. It was estimated that the maximum achievable DAT occupancy was about 80% and that half of this effect was accomplished by approximately 0.25 mg TE and a plasma drug concentration of 4 ng/ml. The results indicated an important mechanism of action of TE on DAT. Further, these results suggest that the previously reported dose-dependent weight loss, in TE treated subjects, was in part mediated by an up-regulation of dopaminergic pathways due to enhanced amounts of synaptic dopamine after blockade of DAT.

  • 76.
    Artursson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, C A S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Computational approaches to drug absorption and bioavailability. 17. Intestinal absorption; the role of polar surface area.2003In: Drug Bioavailability – Estimation of Solubility, Permeability, Absorption and Bioavailability, Wiley , 2003, p. 341-Chapter in book (Other scientific)
  • 77.
    Artursson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Borchardt, RT
    Intestinal drug absorption and metabolism in cell cultures: Caco-2 and beyond1997In: PHARMACEUTICAL RESEARCH, Vol. 14, p. 1655-Article in journal (Refereed)
  • 78.
    Artursson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Karlsson, J
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Ocklind, G
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Schipper, N
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Studying transport in absorptive epithelia1996In: Cell models of epithelial tissues - A practical approach, IRL, Oxford , 1996, Vol. 6, p. 111-Chapter in book (Other scientific)
  • 79.
    Artursson, P
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lazorova, L
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Transcellular delivery of peptide antigens across the intestinal epithelial barrier. In Peptide and protein drug research1998Other (Other academic)
  • 80.
    Artursson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Matsson, P
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Cell culture absorption models - state of the art2006In: Pharmacokinetic profiling in drug research: Biological. physicochemical and computational stragies, Wiley-VCH, Zürich , 2006, p. 71-Chapter in book (Refereed)
  • 81.
    Artursson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Neuhoff, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Tavelin, S
    Matsson, P
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Passive permeability and active transport models for the prediction of oral absorption2007In: Comprehensive medicinal chemistry vol 5: Cellular in vitro tools in ADMET, Elsevier , 2007, p. 259-278Chapter in book (Refereed)
  • 82.
    Artursson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Palm, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Luthman, K
    Department of Medicinal Chemistry.
    Caco-2 monolayers in experimental and theoretical predictions of drugtransport.2001In: Adv. Drug Deliv. Rev., Vol. 46, p. 27-Article in journal (Refereed)
  • 83.
    Artursson, P
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Tavelin, S
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Studies of membrane permeability and oral absorption 6: Caco-2 and emerging alternatives for prediction of intestinal drug transport: A general overview.2003In: Drug Bioavailability - Estimation of Solubility, Permeability, Absorption and Bioavailability, Wiley , 2003, p. 72-Chapter in book (Other scientific)
  • 84.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy. Uppsala Univ, Uppsala, Sweden.
    Experimental approaches to understand intracellular based drug bioavailability2019In: Drug Metabolism and Pharmacokinetics, ISSN 1347-4367, E-ISSN 1880-0920, Vol. 34, no 1, p. S3-S3Article in journal (Other academic)
  • 85.
    Artursson, Per
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    New cell-based approaches for better predictions of drug transport and cellular drug exposure2016In: Drug metabolism reviews (Softcover ed.), ISSN 0360-2532, E-ISSN 1097-9883, Vol. 48, p. 7-7Article in journal (Other academic)
  • 86.
    Artursson, Per
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Knight, Stefan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Structure and Molecular Biology.
    Breaking the intestinal barrier to deliver drugs2015In: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 347, no 6223, p. 716-717Article in journal (Other academic)
  • 87.
    Artursson, Per
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Matsson, Pär
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Absorption Prediction2004In: Profiling in Drug Discovery for Lead Selection, AAPS Press, Arlington VA , 2004Chapter in book (Refereed)
  • 88.
    Artursson, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Matsson, Pär
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Karlgren, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    In vitro characterization of interactions with drug transporting proteins2013In: Transporters in Drug Development : Discovery, Optimization, Clinical Study and Regulation / [ed] Steffansen B, Sugiyama Y, New York: Springer, 2013, p. 37-65Chapter in book (Refereed)
  • 89.
    Artursson, Per
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Palm, Katrin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Luthman, Kristina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Caco-2 monolayers in experimental and theoretical predictions of drug transport2012In: Advanced Drug Delivery Reviews, ISSN 0169-409X, E-ISSN 1872-8294, Vol. 64, no S, p. 280-289Article, review/survey (Refereed)
    Abstract [en]

    This review examines the use of Caco-2 monolayers in the prediction of intestinal drug absorption. First, the different routes of drug transport in Caco-2 monolayers are compared with those seen in vivo. Second, the prediction of drug absorption in vivo from transport experiments in cell monolayers is discussed for different classes of drugs. Finally, the use of Caco-2 monolayers as a reference model in physico-chemical and theoretical predictions of drug absorption is discussed. We conclude that Caco-2 monolayers can be used to identify drugs with potential absorption problems, and possibly also to select drugs with optimal passive absorption characteristics from series of pharmacologically active molecules generated in drug discovery programs.

  • 90.
    Arvidsson, Björn
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Allard, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Sjögren, Erik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Lennernäs, Hans
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Sjöberg, Per Johan Ragnar
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Bergquist, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Physical and Analytical Chemistry.
    Online capillary solid phase extraction and liquid chromatographic separation with quantitative tandem mass spectrometric detection (SPE-LC-MS/MS) of ximelagatran and its metabolites in a complex matrix.2009In: Journal of chromatography. B, ISSN 1570-0232, E-ISSN 1873-376X, Vol. 877, no 3, p. 291-297Article in journal (Refereed)
    Abstract [en]

    This work presents the development and validation of a fully automated quantitative analysis method of melagatran, its prodrug ximelagatran, and its major metabolites for the study of drug behavior in biofluids. The method involves online sample clean-up and enrichment on a C4 capillary column followed by separation on a capillary C18 column. Electrospray ionization tandem mass spectrometric detection in positive ion mode was performed with multiple reactions monitoring of eight different transients, divided into two time segments with four transients each. The structural similarity, the complexity of the matrix (pig liver extract) and the formation of isobaric fragment ions, made efficient chromatographic separation necessary. The analysis method provides valid accuracy (<9%; RSD%), precision (<8%; RSD%), linearity (<1.2 nM–1 μM; R2 > 0.999), limit of quantitation (<3.6 nM), retention repeatability (<1.2%; RSD%), selectivity, as well as analyte and column stabilities over a wide concentration range.

  • 91.
    Arvén, Ottilia
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Using Upsalite® as drug delivery vehicle: Increasing the solubility of poorly soluble drugs by stabilizing their amorphous state2017Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Poor aqueous solubility is an issue not only in drug discovery and development but also for registered drug products, since poor drug solubility is often related to poor absorption (bioavailability). There are several methods available to increase the aqueous solubility and dissolution rate of pharmaceutical formulations. One new way is to incorporate the drug into mesopores, which suppresses crystallization of the drug and keeps it in an amorphous form. Consequently, the dissolution rate of the substance increases and the bioavailability might thereby be enhanced.

    Researchers at the division of Nanotechnology and Functional Materials at Uppsala University, led by Professor Maria Strømme, have investigated the use of Upsalite® - a mesoporous magnesium carbonate with high surface area and narrow pore size distribution - as drug delivery vehicle. Results showed that Upsalite® stabilized the amorphous state of different model substances and thereby enhanced their aqueous solubility as compared to the free (crystalline) drug.

    The aim of this master thesis was to incorporate four poorly soluble drug compounds into the pores of Upsalite®, followed by a comparison of the in vitro dissolution of these Upsalite®-complexes with the dissolution of corresponding commercially available drug products. The results obtained from powder X-ray diffraction showed that three out of four drug compounds were successfully loaded into Upsalite® in their amorphous state. Furthermore, results from in vitro studies in simulated intestinal fluid (pH 6.8) presented enhanced dissolution of each substance loaded into Upsalite®, as compared to their commercial equivalents. Lastly, the amorphous state of the three drug substances successfully incorporated into the pores of Upsalite®, was stable for at least one month when stored in room temperature at 75 percent relative humidity.

  • 92. Asakawa, Tsuyoshi
    et al.
    Ishino, Shouhei
    Hansson, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy. Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Almgren, Mats
    Department of Physical Chemistry. Teknisk-naturvetenskapliga vetenskapsområdet, Chemistry, Department of Physical and Analytical Chemistry, Physical Chemistry I.
    Ohta, Akio
    Miyagishi, Shigeyoshi
    Appearance of pure fluorocarbon micelles surveyed by fluorescence quenching of amphiphilic quinoline derivatives in fluorocarbon and hydrocarbon surfactant mixtures.2004In: Langmuir, ISSN 0743-7463, Vol. 20, no 17, p. 6998-7003Article in journal (Refereed)
  • 93. Ashton, M
    et al.
    Johansson, L
    Thornqvist, A S
    Svensson, Ulrika S H
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat1999In: Xenobiotica, ISSN 0049-8254, E-ISSN 1366-5928, Vol. 29, no 2, p. 195-204Article in journal (Refereed)
    Abstract [en]

    1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg(-1)) or i.p. (50 mg.kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95 % confidence interval: 10.4, 13.0) l.h(-1).kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) I.h(-1).kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was similar to 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8+/-2.0%) compared with the female rat (11.7+/-2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.

  • 94. Avdeef, Alex
    et al.
    Artursson, Per
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Neuhoff, Sibylle
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Lazorova, Lucia
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Gråsjö, Johan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Tavelin, Staffan
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Caco-2 permeability of weakly basic drugs predicted with the Double-Sink PAMPA pK flux a method.2005In: Eur J Pharm Sci, ISSN 0928-0987, Vol. 24, no 4, p. 333-49Article in journal (Refereed)
  • 95. Aziz, Emad F
    et al.
    Gråsjö, Johan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Forsberg, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Soft X-Ray Physics.
    Andersson, Egil
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Soft X-Ray Physics.
    Söderström, Johan
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics. Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Molecular and condensed matter physics.
    Duda, Laurent
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics.
    Zhang, Wenhua
    Yang, Jinglong
    Eisebitt, Stefan
    Bergström, Christel
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Luo, Yi
    Nordgren, Joseph
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Materials Science, Surface and Interface Science.
    Eberhardt, Wolfgang
    Rubensson, Jan-Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics.
    Photoinduced Formation of N2 Molecules in Ammonium Compounds2007In: Journal of Physical Chemistry A, ISSN 1089-5639, E-ISSN 1520-5215, Vol. 111, no 39, p. 9662-9669Article in journal (Refereed)
    Abstract [en]

    Via fluorescence yield (FY) and resonant inelastic scattering spectroscopy in the soft X-ray range we find that soft X-rays induce formation of N2 molecules in solid NH4Cl and in related compounds. The nitrogen molecules form weak bonds in NH4Cl, so that a substantial fraction of the molecules remains in the sample. From measurements of the FY as a function of exposure and temperature, the rates for the photochemical processes are estimated. At elevated temperatures (363 K), several nitrogen atoms are removed from the sample per incoming photon. At lower temperatures (233 K), the rate is reduced to around 0.02 nitrogen atoms for each incoming photon. Virtually all these atoms form N2 molecules which are bound in the sample. The generality and implications of these results are briefly discussed.

  • 96.
    Bardage, C
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Isacson, D
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Hypertension and health-related quality of life: An epidemiological study in Sweden.2001In: J Clin Epidemiol, Vol. 54, p. 172-Article in journal (Refereed)
  • 97.
    Bardage, C
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Isacson, D
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Pedersen, NL
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Self-rated health as a predictor of mortality among persons with cardiovascular diseases in Sweden2001In: Scand J Public Health, Vol. 29, p. 13-Article in journal (Refereed)
  • 98.
    Bardage, C
    et al.
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Isacson, D
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Ring, L
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Bingefors, K
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    A Swedish population based study on the relationship between the SF-36 and health utilities to measure health in hypertension2003In: Blood Pressure, Vol. 4, p. 203-Article in journal (Refereed)
  • 99.
    Bardage, Carola
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Pharmacy.
    Cardiovascular disease and hypertension: Population-based studies on self-rated health and health-related quality of life in Sweden2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim with this thesis was to study cardiovascular disease and hypertension, use of drugs and health from an epidemiological perspective. Various methods - self-rated health (SRH), health related quality of life (HRQL) - the 36-item short form questionnaire (SF-36) - and health utility measurements - the rating scale (RS) and the time-trade off (TTO) methods - were employed.

    Data from the Swedish Adoption/Twin Study of Aging (SATSA) in 1984, 1987, 1990, and 1993 as well as a general population survey conducted in Uppsala County in 1995 were used.

    Persons who have cardiovascular disease, both with and without drug treatment, were found to have a lower SRH as compared to others in the population. Longitudinal analyses showed that SRH was relatively stable over time among persons with cardiovascular disease. Both having a low SRH and having cardiovascular disease were associated with a higher mortality rate.

    Hypertensives were found to have a lower HRQL than do others in the general population as measured by the SF-36. The lowest scoring was found in the general health perception scale (GH), whereas role emotional (RE) and mental health (MH) were the scales least affected by hypertension.

    Nearly 20 percent of the antihypertensive drug users reported side effects.The pattern of side effects was similar to that reported in clinical trials. Both hypertension itself and the drug treatment were found to have an impact on the patient's health-state utility as measured by the RS. Comparative analyses showed that health utilities and psychometric quality-of-life instruments were only moderately correlated among hypertensives.

    The results also showed that inequalities in HRQL were present with respect to several sociodemographic factors.

    In summary, this thesis revealed that persons with cardiovascular disease and/or with hypertension experience poorer health than others in the population. The poor health may be caused both by the disease and/or the drug treatment. The results in this thesis also suggested that special attention and care should be directed to persons with cardiovascular disease and/or hypertension reporting ill health. This especially is important given that low HRQL can be a riskfactor for subsequent cardiovascular events or complications which in turn might result in higher mortality rate.

  • 100.
    Bardage, Carola
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Ekedahl, Anders
    Ring, Lena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Health-Care Professionals' Perspectives on Multi-Dose Dispensed Medicines2013In: Pharmacoepidemiology and Drug Safety, ISSN 1053-8569, E-ISSN 1099-1557, Vol. 22, no S1, p. 251-251Article in journal (Other academic)
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