| 1. |
- Axelsson, Anders, et al.
(författare)
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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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Ingår i: Optics and Lasers in Engineering. - : Elsevier BV. - 0143-8166. ; 46:12, s. 865-876
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Tidskriftsartikel (refereegranskat)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. |
- Cuppok, Y., et al.
(författare)
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Drug release mechanisms from Kollicoat SR:Eudragit NE coated pellets
- 2011
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 409:1-2, s. 30-37
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Kaunisto, Erik, et al.
(författare)
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Dissolution Kinetics or Pure Mass Transfer? A Mechanistic Study of Dissolution
- 2011
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Ingår i: AIChE Journal. - : Wiley. - 1547-5905 .- 0001-1541. ; 57:10, s. 2610-2617
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Kaunisto, Erik, et al.
(författare)
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Mechanistic modelling of drug release from polymer-coated and swelling and dissolving polymer matrix systems.
- 2011
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 418, s. 54-77
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Marucci, Mariagrazia, et al.
(författare)
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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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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 136, s. 206-212
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Marucci, Mariagrazia, et al.
(författare)
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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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Ingår i: Journal of Physics D: Applied Physics. - : IOP Publishing. - 1361-6463 .- 0022-3727. ; 40:9, s. 2870-2880
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Marucci, Mariagrazia, et al.
(författare)
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Electronic speckle pattern interferometry: A novel non-invasive tool for studying drug transport rate through free films
- 2006
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 114:3, s. 369-380
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Tidskriftsartikel (refereegranskat)abstract
- In this work, Electronic Speckle Pattern Interferometry (ESPI) is presented as a non-invasive tool to study drug transport in controlled release systems. ESPI is shown to be a feasible tool to measure drug film permeability via comparison with an ordinary diaphragm cell. A specially designed cuvette was used in the release study: the polymeric film separated the donor and the receiving chambers of the cuvette to create a diffusion cell with no mixing in the two chambers. Thus, the cuvette mimicked a coated system immersed in a stagnant bulk liquid. Concentration profile data were obtained for the two compartments. Using these data, it was possible to visually discriminate between a film subject only to diffusion and a film subject to diffusion as well as osmotic effects. Moreover, using the concentration profile data collected at different time intervals, it was possible to follow the film properties in terms of drug permeability, thus studying bow drug permeability depended on drug concentration. Compared to other measuring techniques, ESPI offers the advantages that no invasive measurements are needed, and that no sampling and calibration are required. Furthermore, the permeability can be measured with no influence of mass transfer in the boundary layers. (c) 2006 Elsevier B.V. All rights reserved.
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| 8. |
- Marucci, Mariagrazia, et al.
(författare)
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Evaluation of osmotic effects on coated pellets using a mechanistic model
- 2007
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 336:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to develop a simple experimental methodology and to develop a mechanistic model to characterize the release mechanism from pellets developing cracks during the release process with special focus on osmotic effects. The release of remoxipride from pellets coated with an ethyl cellulose film was chosen as a case study. Dose release experiments at different bulk osmotic pressures revealed that the release process was mainly osmotically driven. The model was used to calculate the solvent permeability of the coating, 1.1 x 10(-10) m(2) h(-1) MPa-1 The model was validated by release experiments using similar pellets having different coating thicknesses. The effective diffusion coefficient of remoxipride in the coating was also calculated and found to be 1.7 x 10(-1) m(2) h(-1). A series of experiments was performed in which the osmotic pressure of the receiving solution was changed during the experiment. From the results of these experiments, the area of the cracks in the film, formed by the hydrostatic pressure built up inside the pellets, was estimated to be 3.5 x 10(-5) m(2)/m(2) coating. It could also be deduced that the solvent permeability of the coating film was affected by swelling in the same way at different osmotic pressures. (C) 2006 Elsevier B.V. All rights reserved.
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| 9. |
- Marucci, Mariagrazia, et al.
(författare)
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Mechanistic model for drug release during the lag phase from pellets coated with a semi-permeable membrane.
- 2008
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 127, s. 31-40
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Tidskriftsartikel (refereegranskat)abstract
- A new mechanistic model of drug release during the lag phase from coated pellets undergoing cracking in the coating due to the hydrostatic pressure built up inside the pellet has been developed. The model describes dynamically all the main release processes occurring during the lag phase in pellets coated with a semi-permeable membrane, i.e. the influx of solvent driven by the difference in osmotic pressure across the coating, dissolution of the drug, swelling of the pellet due to solvent accumulation, build-up of hydrostatic pressure inside the pellet, tensile stress acting on the coating, and the efflux of the dissolved drug. The water uptake is described using irreversible thermodynamics theory, while the tensile stress is described using solid mechanics theory. Importantly, the model allows the prediction of the lag time prior to crack formation. The effect of the pellet size, the pellet shape and the coating thickness on the lag time and on the lag phase release profile has been investigated via computer simulations. The model was validated by comparison with dose release data obtained from pellets coated with an ethyl-cellulose-based film. The good agreement found between the predicted release and the experimental data confirmed the validity of the model.
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| 10. |
- Marucci, Mariagrazia, et al.
(författare)
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Osmotic pumping release from ethyl-hydroxypropyl-cellulose-coated pellets: A new mechanistic model.
- 2010
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 1873-4995 .- 0168-3659. ; 142, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- A new mechanistic model of drug release by osmotic pumping and diffusion from pellets coated with a semipermeable film developing pores created by the leaching of water-soluble compounds initially present in the coating, has been developed. The model describes dynamically all the main processes occurring during release, i.e. the inflow of solvent driven by the difference in osmotic pressure across the coating film, dissolution of the drug, swelling of the pellet due to mass accumulation, the build-up of hydrostatic pressure inside the pellet, and the outflow of the dissolved drug through the pores. The model was validated by comparison with the release profile of single metoprolol succinate pellets coated with a film made of ethyl cellulose and hydroxypropyl cellulose (80:20). This system was chosen as it was shown that the release mechanism was osmotic pumping, and that the release occurred through small pores created in the coating by hydroxypropyl cellulose leaching. Insight into the release process was obtained via dose release experiments performed at different osmotic pressures of the release medium, single-pellet release experiments, and a study of the coating before and after immersion in the release medium using scanning electron microscopy. The good agreement found between the predicted release and the experimental data confirmed the validity of the model and its prediction capacity. The model can be used to calculate important variables, e.g. the drug concentration profile in a pore and the pressure build-up inside the pellet.
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