| 1. |
- Axelsson, Anders, et al.
(author)
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The use of holographic interferometry and electron speckle pattern interferometry for diffusion measurement in biochemical and pharmaceutical engineering applications
- 2008
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In: Optics and Lasers in Engineering. - : Elsevier BV. - 0143-8166. ; 46:12, s. 865-876
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Journal article (peer-reviewed)abstract
- In this review holographic interferometry and electron speckle pattern interferometry are discussed as efficient techniques for diffusion measurements in biochemical and pharmaceutical applications. Transport phenomena can be studied, quantitatively and qualitatively, in gels, liquids and membranes. Detailed information on these phenomena is required to design effective chromatography bioseparation processes using gel beads or ultrafiltration membranes, and in the design of control led-release pharmaceuticals using membrane-coated pellets or tablets. The influence of gel concentration, ion strength in the liquid and the size of diffusing protein molecules can easily be studied with good accuracy. When studying membranes, the resistance can be quantified, and it is also possible to discriminate between permeable and semi-permeable membranes. In this review the influence of temperature, natural convection and light deflection on the accuracy of the diffusion measurements is also discussed. (c) 2008 Elsevier Ltd. All rights reserved.
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| 2. |
- Bernin, Diana, 1979, et al.
(author)
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Real time MRI to elucidate the functionality of coating films intended for modified release
- 2019
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In: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 311-312, s. 117-124
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Journal article (peer-reviewed)abstract
- Polymer films based on mixtures of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC) have been widely used to coat pellets and tablets to modify the release profile of drugs. For three different EC/HPC films we used 1H and 19F MRI in combination with a designed release cell to monitor the drug, polymer and water in 5 dimensional (5D) datasets; three spatial, one diffusion or relaxation and a temporal dimension, in real time. We observed that the water inflow through the films correlated with the initiation of the dissolution of the drug in the tablet beneath the film. Leaching of the pore forming HPC further accelerated water penetration and resulted in a drug release onset after a hydrostatic pressure was generated below the film indicated by positional changes of the film. For the more permeable film, both water ingress and drug egress showed a large variability of release over the film surface indicating the heterogeneity of the system. Furthermore, the 1H diffusion dataset revealed the formation of a gel layer of HPC at the film surface. We conclude that the setup presented provides a significant level of details, which are not achieved with traditional methods.
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| 3. |
- Cuppok, Y., et al.
(author)
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Drug release mechanisms from Kollicoat SR:Eudragit NE coated pellets
- 2011
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 409:1-2, s. 30-37
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Journal article (peer-reviewed)abstract
- Thin, free films based on Kollicoat SR:Eudragit NE blends were prepared by casting or spraying aqueous dispersions of these polymers, and were thoroughly characterized with respect to their water uptake behavior, water permeability, dry mass loss kinetics, mechanical properties and drug release patterns. A mechanistic mathematical model based on Fick's law of diffusion was used to quantify the experimentally measured release of metoprolol succinate from various types of systems. With increasing Eudragit NE content the films became more hydrophobic, resulting in decreased water permeability as well as water uptake rates and extents. In addition, the dry mass loss upon exposure to the release medium decreased. Consequently, the films' permeability for the drug decreased. Importantly, metoprolol succinate release from thin films was mainly controlled by pure diffusion, allowing for the determination of the apparent diffusion coefficient of the drug in the different polymeric systems. Knowing these values, drug release from coated pellets could be quantitatively predicted, assuming intact film coatings throughout the observation period. Comparison with independent experimental results showed that crack formation set on very rapidly in the polymeric membranes upon exposure to the release medium in the case of sugar starter cores, irrespective of the polymer:polymer blend ratio and investigated coating level. In contrast, the onset of crack formation was delayed as a function of the blend ratio and coating thickness in the case of microcrystalline cellulose starter cores, attracting less water into the pellets core. The obtained new insight into the underlying drug release mechanisms can be very helpful during device optimization and improve the safety of this type of advanced drug delivery systems. (C) 2011 Elsevier B.V. All rights reserved.
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| 4. |
- Gebäck, Tobias, 1977, et al.
(author)
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Investigation of the Effect of the Tortuous Pore Structure on Water Diffusion through a Polymer Film Using Lattice Boltzmann Simulations
- 2015
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In: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 119:16, s. 5220-5227
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Journal article (peer-reviewed)abstract
- Understanding how the pore structure influences the mass transport through a porous material is important in several applications, not the least in the design of polymer film coatings intended to control drug release. In this study, a polymer film made of ethyl cellulose and hydroxypropyl cellulose was investigated. The 3D structure of the films was first experimentally characterized using confocal laser scanning microscopy data and then mathematically reconstructed for the whole film thickness. Lattice Boltzmann simulations were performed to compute the effective diffusion coefficient of water in the film and the results were compared to experimental data. The local porosities and pore sizes were also analyzed to determine how the properties of the internal film structure affect the water effective diffusion coefficient. The results show that the top part of the film has lower porosity, lower pore size, and lower connectivity, which results in a much lower effective diffusion coefficient in this part, largely determining the diffusion rate through the entire film. Furthermore, the local effective diffusion coefficients were not proportional to the local film porosity, indicating that the results cannot be explained by a single tortuosity factor. In summary, the proposed methodology of combining microscopy data, mass transport simulations, and pore space analysis can give valuable insights on how the film structure affects the mass transport through the film.
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| 5. |
- Häbel, Henrike, 1987, et al.
(author)
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A three-dimensional anisotropic point process characterization for pharmaceutical coatings
- 2017
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In: Spatial Statistics. - : Elsevier BV. - 2211-6753. ; 22:2, s. 306-320
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Journal article (peer-reviewed)abstract
- © 2017 Elsevier B.V. Spatial characterization and modeling of the structure of a material may provide valuable knowledge on its properties and function. Especially, for a drug formulation coated with a polymer film, understanding the relationship between pore structure and drug release properties is important to optimize the coating film design. Here, we use methods from image analysis and spatial statistics to characterize and model the pore structure in pharmaceutical coatings. More precisely, we use and develop point process theory to characterize the branching structure of a polymer blended film with data from confocal laser scanning microscopy. Point patterns, extracted by identifying branching points of pore channels, are both inhomogeneous and anisotropic. Therefore, we introduce a directional version of the inhomogeneous K-function to study the anisotropy and then suggest two alternative ways to model the anisotropic three-dimensional structure. First, we apply a linear transformation to the data such that it appears isotropic and subsequently fit isotropic inhomogeneous Strauss or Lennard-Jones models to the transformed pattern. Second, we include the anisotropy directly in a Lennard-Jones and a more flexible step-function model with anisotropic pair-potential functions. The methods presented will be useful for anisotropic inhomogeneous point patterns in general and for characterizing porous material in particular.
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| 6. |
- Kaunisto, Erik, et al.
(author)
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Dissolution Kinetics or Pure Mass Transfer? A Mechanistic Study of Dissolution
- 2011
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In: AIChE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 57:10, s. 2610-2617
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Journal article (peer-reviewed)abstract
- In many cases, classic in vitro tests are used to investigate dissolution from powders and solids. A problem with these kinds of tests is the frequent use of agitation, leading to a lumped description of the properties at the solid-liquid intetface. The hydrodynamic forces arising from agitation might have a nontrivial impact on the dissolution properties, thus calling for a comparison of results with those stemming from stagnant dissolution with the aim to increase the understanding of the dissolution process. Stagnant dissolution of compressed solid benzoic acid was examined using the noninvasive electronic speckle pattern interferometry technique in this study. The diffusion coefficient for benzoic acid in 37 degrees C water was measured using the same technique, and, by combining the results, the surface kinetics at the solid-liquid intetface were calculated. A comparison with previous dissolution data from a rotating disk suggests that the presence of convection can increase the observed surface kinetics. (C) 2010 American Institute of Chemical Engineers AlChE J, 57: 2610-2617, 2011
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| 7. |
- Kaunisto, Erik, et al.
(author)
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Mechanistic modelling of drug release from polymer-coated and swelling and dissolving polymer matrix systems.
- 2011
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In: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 418, s. 54-77
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Journal article (peer-reviewed)abstract
- The time required for the design of a new delivery device can be sensibly reduced if the release mechanism is understood and an appropriate mathematical model is used to characterize the system. Once all the model parameters are obtained, in silico experiments can be performed, to provide estimates of the release from devices with different geometries and compositions. In this review coated and matrix systems are considered. For coated formulations, models describing the diffusional drug release, the osmotic pumping drug release, and the lag phase of pellets undergoing cracking in the coating due to the build-up of a hydrostatic pressure are reviewed. For matrix systems, models describing pure polymer dissolution, diffusion in the polymer and drug release from swelling and eroding polymer matrix formulations are reviewed. Importantly, the experiments used to characterize the processes occurring during the release and to validate the models are presented and discussed.
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| 8. |
- Marucci, Mariagrazia
(author)
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Characterization of the Mechanisms of Drug Release from Polymer-Coated Formulations using Experiments and Modelling
- 2009
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Doctoral thesis (other academic/artistic)abstract
- The main objectives of the work presented in this thesis were to develop new experimental methods to improve the understanding of the release mechanism from a coated formulation and to develop new mechanistic models to describe the release process for pellets coated with a semi-permeable film. Another aim was to characterize the release mechanism from a formulation coated with films made of a blend of a water-insoluble polymer, ethyl cellulose (EC), and a water-soluble polymer, hydroxypropyl cellulose (HPC). The work dealt with free films intended for coating and with coated multiple-unit systems. Two methodologies were mainly used in the study of free films. Electronic speckle pattern interferometry made it possible to discriminate between a semi-permeable and a permeable film. For a permeable film, the effective diffusion coefficient of a drug in the film was determined. A new release cell equipped with a manometer was developed. The combination of pressure and release data made it possible to easily and accurately characterize the release mechanism, to discriminate between semi-permeable and permeable films, and to detect changes in the structure of the film and in the release mechanism during the release. A mechanistic model describing the lag phase of pellets coated with a semi-permeable film undergoing cracking due to hydrostatic pressure build-up was developed. The model was validated against experimentally determined whole-dose release profiles of pellets coated with an EC-based film. The model showed that a small variation in the film thickness has a significant influence on the lag time. A mechanistic model to describe the osmotic pumping release from pellets coated with a semi-permeable film containing water-filled channels was also developed. The model was validated by comparison with experimentally determined release profiles of single pellets coated with a film made of EC and HPC. Via model simulation it was found that the concentration profile in the channels was almost constant. The HPC content of EC/HPC films affects the amount of HPC leached out of the films, and thus the release mechanism. The release mechanism changed from osmotic pumping to diffusion as the amount of HPC increased. When release occurs by diffusion, the effective diffusion coefficient of a drug in the coating is not constant but increases significantly during the release process as a consequence of HPC leaching.
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| 9. |
- Marucci, Mariagrazia, et al.
(author)
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Coated formulations: New insights into the release mechanism and changes in the film properties with a novel release cell.
- 2009
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In: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 136, s. 206-212
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Journal article (peer-reviewed)abstract
- The effect of the blend ratio of water-insoluble ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC-LF), on the properties of sprayed films and on the drug release mechanism of formulations coated with the material was investigated. When the original HPC-LF content exceeded 22%, both the amount of HPC-LF leached out and the water permeability of the films increased drastically when they were immersed in a phosphate buffer solution. The release mechanism of potassium nitrate through EC/HPC-LF films containing 20, 24 and 30% HPC-LF was elucidated in a new release cell equipped with a manometer to measure the pressure build-up inside the cell. A lag phase in the release accompanied by a pressure build-up was observable in all the experiments showing that all the films were initially semi-permeable to KNO(3). However, pressure data revealed that films with 30% HPC-LF became permeable to KNO(3) during the release process due to HPC-LF leaching. Importantly, the blend ratio influenced not only the release rate (which increased as the amount of HPC-LF increased), and the lag time (which increased as the amount of HPC-LF decreased), but also the release mechanism, which changed from osmotic pumping to diffusion as the amount of HPC-LF increased.
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| 10. |
- Marucci, Mariagrazia, et al.
(author)
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Determination of a diffusion coefficient in a membrane by electronic speckle pattern interferometry: a new method and a temperature sensitivity study
- 2007
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In: Journal of Physics D: Applied Physics. - : IOP Publishing. - 1361-6463 .- 0022-3727. ; 40:9, s. 2870-2880
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Journal article (peer-reviewed)abstract
- In this work, a method has been developed to easily determine the effective diffusion coefficient (D-e) of a solute in a permeable membrane using electronic speckle pattern interferometry. Fringes are introduced parallel to the direction of diffusion during the diffusion process and D-e can be calculated by simple measurements on the interference pattern. For a fast and convenient determination of D-e, a mathematical expression has been derived from the analytical solution of diffusion in two media separated by a resistance. The D-e obtained when fringes are introduced is in agreement with that obtained when fringes are not introduced. The effect of temperature variation on the optical path of the reference and the object beams has also been investigated. The error introduced into the calculation of D-e, when the temperature oscillation is not taken into account, has been compared for the case when fringes are not introduced during the diffusion experiment and the case when fringes are introduced. In the first case, the relative error can be greater than 100%. Interestingly, in the latter case, the error caused by temperature oscillation is considerably reduced, and no error is introduced if the temperature changes homogeneously over the whole diffusion cell used for the diffusion experiment.
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