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  • 1. Elversson, J
    et al.
    Andersson, K
    Fureby-Millqvist, A
    YKI – Ytkemiska institutet.
    An atomic force microscopy approach for assessment of particle density applied to single spray-dried carbohydrate particles2007In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 96, no 4, p. 905-912Article in journal (Refereed)
    Abstract [en]

    To evaluate an atomic force microscopy (AFM) approach for effective density analysis of single spray dried carbohydrate particles in order to investigate the internal structure of the particles. In addition, the AFM method was compared to an established technique, that is gas pycnometry. Resonant frequency AFM analysis was employed for determination of the mass of individual particles of spray-dried lactose, mannitol, and a mixture of sucrose/dextran (4:1). The effective particle density was calculated using the diameter of the spherical particles obtained from light microscopy. The apparent particle density was further analyzed with gas pycnometry. It was observed by microscopy that particles appeared either ‘‘solid’’ or ‘‘hollow.’’ A solid appearance applied to an effective particle density close to the true density of the material, whereas a density around 1 g/cm3 corresponded to a hollow appearance. However, carbohydrates, which crystallized during spray drying, for example, mannitol appeared solid but the average effective particle density was 0.95 g/cm3, indicating a continuous but porous structure. AFM measurements of effective particle density corroborate the suggestion of differences in particle structure caused by the varying propensity of carbohydrates to crystallize during spray drying, resulting in mainly either amorphous hollow orcrystalline porous particles.

  • 2. Elversson, J
    et al.
    Millqvist-Fureby, A
    YKI – Ytkemiska institutet.
    Particle size and density in spray drying - effects of carbohydrate properties2005In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 94, p. 2049-2060Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to examine some fundamental aspects of the particle formation during spray drying, related to particle size and density. Particles were prepared in a laboratory spray dryer from carbohydrates with different solubility and crystallization propensity, such as lactose, mannitol and sucrose/dextran 4:1. The feed concentrations ranged from 1% w/w to saturated and the size of droplets and particles were measured by laser diffraction. Particles were also characterized by various microscopy techniques (i.e. scanning electron microscopy, confocal laser scanning microscopy and light microscopy), differential scanning calorimetry, gas adsorption, and gas pycnometry. As demonstrated larger particles could be obtained by either increasing the droplet size during atomization; increasing the concentration of the feed solution; or decreasing the solubility of the solute. The apparent particle density was found negatively correlated to the feed concentration. Due to the non-linear relationship between the feed concentration and the particle size, it was concluded that higher solids load may cause an increase in the effective particle density and that the reduction in the apparent particle density was a result of a gradually less permeable particle surface. Further, the crystallization propensity of the carbohydrate influenced the particle formation and resulted in either hollow or porous particles

  • 3. Elversson, J
    et al.
    Millqvist-Fureby, A
    YKI – Ytkemiska institutet.
    Alderborn, G
    Elofsson, U
    YKI – Ytkemiska institutet.
    Droplet and particle size relationship and shell thickness of inhalable lactose particles during spray drying2003In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 92, p. 900-910Article in journal (Refereed)
    Abstract [en]

    To find means of controlling the size and density of particles intended for inhalation the relationship between droplet and particle size during spray drying was investigated. Lactose solutions were atomized with a two-fluid nozzle and dried in a laboratory spray drier. The effects of nozzle orifice diameter, atomization airflow and feed concentration on droplet and particle size were examined. Mass median diameter of both droplets and particles were analyzed with laser diffraction. In addition, scanning electron microscopy and transmission electron microscopy were used for studies of particle shape and morphology. It was demonstrated that nozzle orifice diameter and airflow, but not feed concentration controlled the droplet size during atomization. Increasing droplet size increased particle size but the effect was also influenced by feed concentration. Particles from solutions of a low concentration (1% w/w) were smaller than those from higher concentrations (5-20% w/w). This may be partly explained by lower yields at higher feed concentrations, but may also be related to differences in drying rate. Spray-dried lactose solutions formed hollow particles, and it was suggested that the shell thickness of the particles increased with increasing feed concentration

  • 4.
    Friberg, S
    et al.
    YKI – Ytkemiska institutet.
    Larsson, L
    Partition of an organophosphorus compound, dichlorvos, between liquid and liquid crystalline phases1975In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 64, p. 822-825Article in journal (Refereed)
  • 5.
    Friberg, S
    et al.
    YKI – Ytkemiska institutet.
    Mandell, L
    YKI – Ytkemiska institutet.
    Influence of phase equilibria on properties of emulsions1970In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 59, p. 1001-1004Article in journal (Refereed)
  • 6.
    Friberg, S
    et al.
    YKI – Ytkemiska institutet.
    Rydhag, L
    Jederström, G
    Liquid crystalline phases in aerosol formulations : I. phase equilibria in propellant compositions1971In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 60, p. 1883-1885Article in journal (Refereed)
  • 7. Jederström, G
    et al.
    Rydhag, L
    Friberg, S
    YKI – Ytkemiska institutet.
    Liquid crystalline phases in aerosol formation : II. influence of liquid crystalline phases on foam stability1973In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 62, p. 1979-1982Article in journal (Refereed)
  • 8.
    Kronberg, B
    et al.
    YKI – Ytkemiska institutet.
    Dahlman, A
    Carlfors, J
    Carlsson, J
    Artursson, P
    Preparation and evaluation of sterically stabilized liposomes: colloidal stability, serum stability, macrophage uptake and toxicology1990In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 79, p. 667-671Article in journal (Refereed)
    Abstract [en]

    Sterically stabilized liposomes were produced by incorporating a nonionic surfactant, polysorbate 80 (Tween 80), into the lipid bilayer. The sterically stabilized liposomes exhibited a superior entrapment stability compared with surfactant-free liposomes (i.e., liposomes prepared with lipids and cholesterol). The sterically stabilized liposomes were stable at high calcium ion concentrations, and liposome-entrapped carboxyflourescein was retained within the stabilized liposomes in the presence of serum for at least 5 h. The macrophage uptake of the sterically stabilized liposomes was comparable to that of liposomes containing lipids and cholesterol. The sterically stabilized liposomes were non-toxic, in concentrations up to 3.0 mM, to macrophages. These results indicate that polysorbate 80 can be used to produce stable liposomes without changing the uniqe macrophage distribution of this drug delivery system.

  • 9. Sjöström, B
    et al.
    Bergenståhl, B
    YKI – Ytkemiska institutet.
    Kronberg, B
    YKI – Ytkemiska institutet.
    A method for the preparation of submicron particles of sparingly water-soluble drugs by precipitation in oil-in-water emulsions. II. Influence of the emulsifier, the solvent, and the drug substance1993In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 82, p. 584-589Article in journal (Refereed)
    Abstract [en]

    Small particles of two steroids; cholesteryl acetate and b-sitosterol, have been prepared by the following technique: The steroid was dissolved in an organic solvent, which was emulsified in water in the presence of sur--factant, thus giving a water continuous emulsion. As the organic solvent was evaporated the steroid precipitated. One particle was found to form in each emulsion droplet. Particle sizes down to 25 nm were obtained by this method. Particles were prepared from emulsions containing different organic solvents and surfactants and the effect on the size and the colloi--dal stability of the particles were examined. It was found that the final particle suspension is relatively stable provided the initial emulsion is stable. Furthermore, there is a close correlation between the initial emul--sion droplet size and the final particle size. The particle size, therefore, can be varied in the same manner as the size of emulsion droplets, e.g. by changing the emulsification process parameters, the amount and choice of surfactant and the oil/water ratio. Finally, the particle size depends on the choice of solvent and only slightly on the concentration of drug in the oil phase of the emulsion.

  • 10. Sjöström, B
    et al.
    Kronberg, B
    YKI – Ytkemiska institutet.
    Carlfors, J
    A method for the preparation of submicron particles of sparingly water-soluble drugs by precipitation in oil-in-water emulsions. I. Influence of emulsification and surfactant concentration1993In: Journal of Pharmaceutical Sciences, ISSN 0022-3549, E-ISSN 1520-6017, Vol. 82, p. 579-583Article in journal (Refereed)
    Abstract [en]

    In this paper we present a method for the synthesis of small particles of poorly water soluble drug substances using emulsions. In the first place, the drug is dissolved in an organic solvent and a water soluble surfactant is dissolved in water. Secondly, these two solutions are mixed to form an emulsion, where the organic solution is emulsified into small droplets in the aqueous phase. The action of the surfactant is partly to decrease the interfacial tension between the water and the organic solution, thus increasing the ease of emulsification, and partly to stabilize the droplets formed against aggregation, or coalescence. The final step in the process is to remove the organic solvent by evaporation in doing which the drug precipitates and one particle is formed in each droplet. If the surfactant is sufficiently effective in stabilizing the particles formed against coagula--tion, we have a suspension of small spherical drug particles. In this paper we use a model system consisting of cholesteryl acetate and toluene. Particles down to 50 nm were obtained by this method. The sizes of the particles were found to be dependent on the surfactant concentration and the emulsification energy.

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