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  • 1.
    Andersson, Helene
    et al.
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, SIK – Institutet för livsmedel och bioteknik. Chalmers University of Technology, Sweden.
    Hjartstam, Johan
    AstraZeneca, Sweden.
    Stading, Mats
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, SIK – Institutet för livsmedel och bioteknik. Chalmers University of Technology, Sweden.
    Von Corswant, Christian
    AstraZeneca, Sweden.
    Larsson, Anette
    Chalmers University of Technology, Sweden.
    Effects of molecular weight on permeability and microstructure of mixed ethyl-hydroxypropyl-cellulose films2013In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 48, no 42006, p. 240-248Article in journal (Refereed)
    Abstract [en]

    Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations. The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight. Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films. It was found that sprayed films were porous throughout the bulk of the films after water immersion. The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability. A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species. The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions. In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films. Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films.

  • 2. Dahlberg, Carina
    et al.
    Millqvist-Fureby, Anna
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, YKI – Ytkemiska institutet.
    Schuleit, Michael
    Furó, Istvan
    Polymer-drug interactions and wetting of solid dispersions2010In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 39, no 1-3, p. 125-133Article in journal (Refereed)
    Abstract [en]

    We demonstrate the ability of drugs to influence the wetting of solid dispersion tablets in unexpected ways. Five model drugs of different water solubility and ability to interact with the involved polymers were incorporated in hydrophilic polymer matrices, made of either hydroxypropyl methylcellulose (HPMC) or polyvinyl pyrrolidone (PVP). The physical mixtures of all combinations of drug and polymer presented Surface hydrophobicities, as measured by the equilibrium advancing contact angle of water, which are expected for materials that do not influence the interactions of each other with water. However, the solid dispersions containing HPMC deviated from this regular behaviour and displayed contact angles below those of the pure compounds involved. either drug or polymer. This behaviour is explained by changed surface exposure of HPMC side groups, as a result of changes in intermolecular hydrogen bonds. In addition to water contact angle measurements, we employed NMR imaging to monitor the time course of water ingress and swelling.

  • 3.
    Holmbäck, Jan
    et al.
    Stockholm University, Sweden; Lipidor AB, Sweden.
    Rinwa, Vibhu
    Stockholm University, Sweden; Lipidor AB, Sweden.
    Johansson, Jenny
    RISE Research Institutes of Sweden, Materials and Production.
    Håkansson, Joakim
    RISE Research Institutes of Sweden, Materials and Production. Gothenburg University, Sweden.
    Rinwa, Puneet
    Lipidor AB, Sweden.
    Carlsson, Anders
    MediGelium AB, Sweden.
    Herslöf, Bengt
    Lipidea AB, Sweden.
    Preclinical development of sodium fusidate antibiotic cutaneous spray based on water-free lipid formulation system2022In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 176, article id 106250Article in journal (Refereed)
    Abstract [en]

    Topical antibiotics are a key component in the management of mild to moderate skin and soft tissue infections. There are, however, concerns about the emerging bacterial resistance against topical antibacterial agents such as fusidic acid, due to the prolonged treatment period of its marketed dosage forms. Improving the efficacy of topical formulations could potentially shorten the treatment period and avoid the resistance growth. To provide a more effective drug delivery, a water-free lipid-based formulation system (AKVANO®) which can be applied by spraying, has been developed. In the current paper, different formulations containing sodium fusidate were evaluated for their in vitro skin permeability using artificial skin mimicking membranes and antibacterial properties using ex vivo and in vivo skin wound infection models. The novel formulations containing sodium fusidate showed a much higher skin permeation (up to 60% of nominal amount) than the commercially available Fucidin® cream (3%). These formulations also gave a significantly stronger antibacterial effect than Fucidin cream showing a clear dose-response relationship for the sodium fusidate content. A spray product based on the described formulation technology would therefore require a shorter treatment time and thereby lower the risk for the development of bacterial resistance. Spray administration of these formulations provides an even layer on the skin surface from which the solvent quickly evaporates and thereby facilitates a non-touch application where no rubbing is required. © 2022 The Authors

  • 4. Petersson Nordén, TP
    et al.
    Siekmann, B
    Lundquist, S
    Malmsten, M
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, YKI – Ytkemiska institutet.
    Physicochemical characterisation of drug-containing phospholipid-stabilised o/w emulsions for intravenous administration2001In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 13, p. 393-401Article in journal (Refereed)
    Abstract [en]

    Clomethiazole (CMZ) was used as a model drug to be incorporated into an emulsion vehicle. The effects of drug concentration and number of homogenisation steps were evaluated using multiple linear regression. The droplet size, measured as a z-average diameter by photon correlation spectroscopy (PCS), was found to be between 60 and 260 nm in the investigated range of CMZ concentrations, highly dependent on the concentration, but more weakly so on the number of homogenisation steps. Slow-scanning high-sensitivity differential scanning calorimetry (DSC) measurements showed that CMZ depresses the phospholipid chain melting temperature in the emulsion system, whereas (13)C nuclear magnetic resonance (NMR) experiments suggested that the CMZ molecules are to a large extent located in the surface region of the emulsion droplets. This interpretation is compatible with results from NMR self-diffusion measurements, which showed that most of the CMZ molecules are rapidly exchanged between emulsion droplets and the aqueous surrounding. It can be concluded that the surface-active drug CMZ has a significant influence on the characteristics of phospholipid-stabilised emulsions through its ability to interact with the phospholipid interface. Thus, the results underline the importance of characterising drug-lipid interactions for the development of lipid-based formulations.

  • 5. Scherlund, M
    et al.
    Welin-Berger, K
    Brodin, A
    Malmsten, M
    RISE, SP – Sveriges Tekniska Forskningsinstitut, SP Sveriges tekniska forskningsinstitut, YKI – Ytkemiska institutet.
    Local anaesthetic block copolymer system undergoing phase transition on dilution with water2001In: European Journal of Pharmaceutical Sciences, ISSN 0928-0987, E-ISSN 1879-0720, Vol. 14, p. 53-61Article in journal (Refereed)
    Abstract [en]

    The possibility of formulating a local anaesthetic system displaying in situ gelation on dilution with water, as well as its dependence on concentration of active ingredients and pH was investigated. For this purpose Lutrol F68, water, a eutectic mixture of lidocaine and prilocaine and Akoline MCM were mixed in different ratios and investigated using crossed polarisers, small-angle X-ray diffraction, rheology, conductivity and NMR self-diffusion measurements. In particular, an isotropic phase of low viscosity turning into a high viscous hexagonal phase upon dilution with water was found. The increase in viscosity is only weakly dependent on temperature in the temperature range of 20-37 degrees C. The rheology and in vitro drug release of these systems were studied and the elastic modulus was found to be fairly independent of concentration of active ingredients and pH in the investigated region. The in vitro release of lidocaine and prilocaine was found to increase with increasing concentration of the active ingredients and with decreasing pH, the latter as a consequence of the pH-dependent ionisation of these substances. The behaviour of the system is promising from a pharmaceutical point of view, since the isotropic low-viscous phase can be injected into, e.g. a periodontal pocket where the presence of saliva will cause a temporal transition into a rigid hexagonal phase thus making the formulation stay at the application site. At even higher water content, either as a result of longer application time or rinsing with water, the hexagonal phase is effectively dissolved through transformation to a water-rich micellar phase

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