| 1. |
- 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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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- Marucci, Mariagrazia, et al.
(författare)
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Polymer leaching from film coating: Effects on the coating transport properties.
- 2011
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 1873-3476 .- 0378-5173. ; 411, s. 43-48
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Tidskriftsartikel (refereegranskat)abstract
- The release mechanism of metoprolol succinate pellets coated with a blend of a water-insoluble polymer, ethyl cellulose (EC), and a water-soluble polymer, hydroxypropyl cellulose (HPC) is mechanistically explained. The kinetics of drug release and HPC leaching were followed for drug doses. The coating was initially not permeable to the drug, and release started only after a critical amount of the HPC had been leached out. Drug release occurred mainly through pores created in the coating by the HPC dissolution. Single-pellet release experiments were also performed. The coating thickness and size of each pellet were measured. In order to quantitatively characterize the transport properties of the coating of the individual pellets, and to determine the effective diffusion coefficient (D(e)) of the drug in the coating, a mechanistic model was used to fit the single-pellet release data. It was found that D(e) increased with time due to an increase in the amount of HPC leached. It was also found that D(e) was dependent on the coating thickness, and increased more slowly with a thicker coating. This agreed well with the finding that the HPC leaching rate decreased with increasing film thickness.
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