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- Dahlberg, Carina, 1980-
(författare)
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Drugs and polymers in dissolving solid dispersions : NMR imaging and spectroscopy
- 2010
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The number of poorly water-soluble drug substances in the pharmaceutical pipeline is increasing, and thereby also the need to design effective drug delivery systems providing high bioavailability. One favourable formulation approach is preparation of solid dispersions, where dispersing a poorly water-soluble drug in a water-soluble polymer matrix improves the dissolution behaviour and the bioavailability of the drug. However, in order to take full advantage of such formulations the impact of material properties on their performance needs to be investigated. An experimental toolbox has been designed, and applied, for analysing the processes which govern the behaviour of solid pharmaceutical formulations in general, and that of solid dispersions in particular. For the purpose of monitoring multifaceted phenomena in situ during tablet dissolution, nuclear magnetic resonance (NMR) spectroscopy and NMR imaging are superior to many other techniques, both on macroscopic and molecular levels. The versatility of NMR with its isotope and chemical selectivity allows one to follow the influence of the original tablet properties on polymer mobilisation, drug migration and water penetration selectively. Mapping these processes on relevant time scales in dissolving tablets highlighted the gel layer inhomogeneity below the originally dry tablet surface as a key factor for drug release kinetics. Furthermore, NMR relaxometry has been shown to provide novel information about the particle size of the drug and its recrystallisation behaviour within swelling solid dispersions. The NMR experiments have been complemented and supported by investigation of the crystalline state, the powder morphology and the surface composition of the dry solid dispersions. These experiments have been performed by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), powder X-ray diffraction (pXRD), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and dynamic contact angle (DAT) measurements. The methods presented in this thesis provide a new avenue towards better understanding of the behaviour of solid dispersions, which in turn may result in more effective distribution of promising drug candidates despite their low water-solubility.
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| 2. |
- Dahlberg, Carina, et al.
(författare)
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Relationships between solid dispersion preparation process, particle size and drug release : an NMR and NMR microimaging study
- 2010
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier BV. - 0939-6411 .- 1873-3441. ; 76:2, s. 311-319
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Tidskriftsartikel (refereegranskat)abstract
- Solid dispersion tablets prepared by either spray drying or rotoevaporation and exhibiting different grain and pore sizes were investigated under the process of hydration-swelling-gelation. H-2 and H-1 NMR microimaging experiments were used to selectively follow water penetration and polymer mobilization kinetics, respectively, while the drug release kinetics was followed by H-1 NMR spectroscopy. The obtained data, in combination with morphological information by scanning electron microscopy (SEM), reveal a complex process that ultimately leads to release of the drug into the aqueous phase. We find that the rate of water ingress has no direct influence on release kinetics, which also renders air in the tablets a secondary factor. On the other hand, drug release is directly correlated with the polymer mobilization kinetics. Water diffusion into the originally dry polymer grains determines the rate of grain swelling and the hydration within the grains varies strongly with grain size. We propose that this sets the stage for creating homogeneous gels for small grain sizes and heterogeneous gels for large grain sizes. Fast diffusion through water-rich sections of the inhomogeneous gels that exhibit a large mesh size is the factor which yields a faster drug release from tablets prepared by rotoevaporation.
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| 3. |
- Dahlenborg, Hanna, et al.
(författare)
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Investigation of Chocolate Surfaces Using Profilometry and Low Vacuum Scanning Electron Microscopy
- 2011
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Ingår i: Journal of the American Oil Chemists Society. - : Wiley. - 0003-021X .- 1558-9331. ; 88:6, s. 773-783
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Tidskriftsartikel (refereegranskat)abstract
- In this study we establish the use of optical non-contact profilometry combined with low vacuum scanning electron microscopy (LV SEM) for the investigation of lipid surfaces. We illustrate, by using profilometry, a methodology for investigation of chocolate surface topology as a function of time, in the same area of interest. Both qualitative and quantitative data analysis has been performed for profilometry data. Further, relating these results to LV SEM images provides complementary topological information and hence a useful toolkit for the study of the chocolate surface prior and post fat bloom formation. For the demonstration of the successful combination of these two analytical techniques, white chocolate pralines were stored at two temperature-controlled conditions (at 18 A degrees C, and cycled between 15 and 25 A degrees C). Surface properties were then investigated during 36 weeks of storage. The surface images and the roughness parameters indicated distinct development of surface characteristics for the two storage conditions. From the results it is suggested that some imperfections, in the form of pores or protrusions, could play a role in fat bloom development and that there may be different main mechanisms of fat migration taking place for the different storage environments. In the present work, a positive correlation of profilometry data to chocolate surface characteristics and early bloom development has been established. There are indications that early prediction of fat bloom can be possible, however further work needs to be done to quantify prediction of fat bloom.
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| 4. |
- Dahlenborg, Hanna, et al.
(författare)
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Study of the porous structure of white chocolate by confocal Raman microscopy
- 2012
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Ingår i: European Journal of Lipid Science and Technology. - : Wiley. - 1438-7697 .- 1438-9312. ; 114:8, s. 919-926
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Tidskriftsartikel (refereegranskat)abstract
- Confocal Raman microscopy has been shown to be a useful technique for investigation of white chocolate surfaces. The appearance of protrusions and pores, and the distribution of fat, sucrose, and milk powder at and below the surface of white chocolate pralines were investigated using confocal Raman microscopy. Raman horizontal and depth scans showed that the protrusions and pores continue at least 10 mu m into the chocolate shell and that some protrusions and channels mainly consist of fat, while some consisted of a fat layer, leaving a hollow space underneath. Further, the pores and their continuing channels consisted of nothing but air. These findings indicate that the protrusions might be connected to channels where we suggest a pressure driven convective flow of liquid fat from within the chocolate matrix that, depending on temperature, moves up to the surface or goes back into the matrix, leaving an empty pore with a shell of fat at the surface, which in some cases collapse and leaves a hollow pore and channel. Therefore, these findings support that the protrusions could be connected to oil migration in chocolate and, thus, further to fat bloom development. Practical applications: Confocal Raman microscopy can be used to investigate the local distribution of different components in white chocolate. This technique offers the possibility to acquire the local distribution of different components within the sample, with a resolution down to the optical diffraction limit. Further, the analysis can be performed at ambient conditions, without requiring any special sample preparation or marker molecules. The results obtained by using this technique suggest that specific surface imperfections on chocolate could be part of a network of pore structures at and beneath the chocolate surface, which could be related to oil migration and thus, to fat bloom formation.
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