| 1. |
- Andersson, Helene, 1983, et al.
(författare)
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Effects of molecular weight on permeability and microstructure of mixed ethyl-hydroxypropyl-cellulose films
- 2013
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Ingår i: European Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0928-0987 .- 1879-0720. ; 48:1-2, s. 240-248
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Tidskriftsartikel (refereegranskat)abstract
- Films of ethyl cellulose (EC) and water-soluble hydroxypropyl cellulose (HPC) can be used for extended release coatings in oral formulations. The permeability and microstructure of free EC/HPC films with 30% w/w HPC were studied to investigate effects of EC molecular weight. Phase separation during film spraying and subsequent HPC leaching after immersion in aqueous media cause pore formation in such films. It was found that sprayed films were porous throughout the bulk of the films after water immersion. The molecular weight affected HPC leaching, pore morphology and film permeability; increasing the molecular weight resulted in decreasing permeability. A model to distinguish the major factors contributing to diffusion retardation in porous films showed that the trend in permeability was determined predominantly by factors associated with the geometry and arrangement of pores, independent of the diffusing species. The film with the highest molecular weight did, however, show an additional contribution from pore wall/permeant interactions. In addition, rapid drying and increasing molecular weight resulted in smaller pores, which suggest that phase separation kinetics affects the final microstructure of EC/HPC films. Thus, the molecular weight influences the microstructural features of pores, which are crucial for mass transport in EC/HPC films.
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| 2. |
- Andersson, Helene, 1983, et al.
(författare)
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The influence of the molecular weight of the water-soluble polymer on phase-separated films for controlled release
- 2016
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 511:1, s. 223-235
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC) can be used for extended release coatings, where the water-soluble HPC may act as a pore former. The aim was to investigate the effect of the molecular weight of HPC on the microstructure and mass transport in phase-separated freestanding EC/HPC films with 30% w/w HPC. Four different HPC grades were used, with weight averaged molecular weights (Mw) of 30.0 (SSL), 55.0 (SL), 83.5 (L) and 365 (M) kg/mol. Results showed that the phase-separated structure changed from HPC-discontinuous to bicontinuous with increasing Mw of HPC. The film with the lowest Mw HPC (SSL) had unconnected oval-shaped HPC-rich domains, leaked almost no HPC and had the lowest water permeability. The remaining higher Mw films had connected complex-shaped pores, which resulted in higher permeabilities. The highest Mw film (M) had the smallest pores and very slow HPC leakage, which led to a slow increase in permeability. Films with grade L and SL released most of their HPC, yet the permeability of the L film was three times higher due to greater pore connectivity. It was concluded that the phase-separated microstructure, the level of pore percolation and the leakage rate of HPC will be affected by the choice of HPC Mw grade used in the film and this will in turn have strong impact on the film permeability.
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| 3. |
- Fager, Cecilia, 1990, et al.
(författare)
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Correlating 3D porous structure in polymer films with mass transport properties using FIB-SEM tomography
- 2021
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Ingår i: Chemical Engineering Science: X. - : Elsevier BV. - 2590-1400. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Porous polymer coatings are used to control drug release from pharmaceutical products. The coating covers a drug core and depending on the porous structure, different drug release rates are obtained. This work presents mass transport simulations performed on porous ethyl cellulose films with different porosities. The simulations were performed on high spatial resolution 3D data obtained using a focused ion beam scanning electron microscope. The effective diffusion coefficient of water was determined using a diffusion chamber. Lattice Boltzmann simulations were used to simulate water diffusion in the 3D data. The simulated coefficient was in good agreement with the measured coefficient. From the results it was concluded that the tortuosity and constrictivity of the porous network increase with decreasing amount of added hydroxypropyl cellulose, resulting in a sharp decrease in effective diffusion. This work shows that high spatial resolution 3D data is necessary, and that 2D data is insufficient, in order to predict diffusion through the porous structure with high accuracy.
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| 4. |
- Larsson, Mikael, 1982, et al.
(författare)
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Effect of ethanol on the water permeability of controlled release films composed of ethyl cellulose and hydroxypropyl cellulose
- 2010
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Ingår i: European Journal of Pharmaceutics and Biopharmaceutics. - : Elsevier BV. - 1873-3441 .- 0939-6411. ; 76:3, s. 428-432
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Tidskriftsartikel (refereegranskat)abstract
- The robustness of controlled release formulations when co-ingested with alcohol is a current concern expressed by regulatory authorities, especially with regard to dose dumping. One such controlled release formulation commonly used is film coating composed of ethyl cellulose (EC) and hydroxypropyl cellulose (HPC). The aim of this study was to investigate how the presence of ethanol in the dissolution medium affects the water permeability of such films. Film samples were prepared in various EC–HPC compositions, and the effect of different ethanol concentrations in the dissolution medium on the permeability was studied using a modified Ussing chamber and tritiated water. It was found that the effect of ethanol on the film permeability varied depending on the composition of the films. The results were interpreted in terms of swelling of the EC in the films, where the swelling increased with increasing ethanol concentration. Thus, for films with low HPC content (non-interconnected pores), the water permeability of the films increased with increasing ethanol concentration as the diffusion through the ethyl cellulose increased due to swelling. However, for films with higher HPC content (having interconnected pores through the films), the permeability decreased, likely due to the swelling of the ethyl cellulose blocking the pores. The interpretation of the results was supported by dynamic mechanic analysis and SEM analysis.
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| 5. |
- Bernin, Diana, 1979, et al.
(författare)
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Real time MRI to elucidate the functionality of coating films intended for modified release
- 2019
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Ingår i: Journal of Controlled Release. - : Elsevier BV. - 0168-3659 .- 1873-4995. ; 311-312, s. 117-124
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Hjärtstam, Johan, 1962
(författare)
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Ethyl Cellulose Membranes used in Modified Release Formulations
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Ethyl cellulose (EC) is a commonly used polymer in modified drug release formulations. The general aim of the present study was to investigate release mechanisms through non-porous EC membranes with hydroxypropyl methyl cellulose (HPMC) contents ranging from 0 to 30% by weight. Experiments on free films and coated drug particles reveal that the drug release is governed by an osmotic pump mechanism for EC membranes with an HPMC content up to 24 wt%. In a novel pressurized cell, it was found that, to make the film permeable to potassium chloride (model substance), it must be submitted to a stress provided by a hydrostatic pressure in the core. Water is imbibed by osmosis and produces the tensile stress. Furthermore, when examining drug pellets it was concluded that the hydrostatic pressure in the core caused a volume increase. As soon as the release began, the volume expansion ended. It is suggested that the tensile stress produces small alterations, microvoids, in the membrane which affect the transport properties of the coating. Increasing the HPMC content in the film lowered the magnitude of the applied tensile stress required to induce permeability. When the amount of HPMC exceeded 24 wt%, the leaching of the water-soluble polymer was significant. This re-sulted in pore formation, which increased the diffusive release of the drug. The knowledge gained on EC membranes produced by a phase separation technique, using ethanol and water, reveals that water permeability and the release rate profiles are drastically changed by an increase of the non-solvent in the liquid-liquid demixing process. Finally, a study is presented in which the hydroxyl group content in the EC chain lies between 2.76 and 3.11 wt%. The results indicate that the modulus of elasticity of a free film decreases as the hydroxyl group content increases. This is thought to be due to the lower solubility of EC with a lower degree of substitution, as determined by the Huggins interaction constant in the film- forming solution, and the ability of the film with a high hydroxyl group content to hold more water. A study on spray-coated pellets was performed and revealed that the release rate is higher in EC with a lower degree of substitution. This observation is in agreement with water permeability measurements on free films.
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| 7. |
- Larsson, Mikael, 1982, et al.
(författare)
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Novel nanostructured microfibrillated cellulose–hydroxypropyl methylcellulose films with large one-dimensional swelling and tunable permeability
- 2012
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617. ; 88:2, s. 763-771
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Tidskriftsartikel (refereegranskat)abstract
- Microfibrillated cellulose (MFC) films containing the water soluble and pharmaceutically approved polymer hydroxypropyl methylcellulose (HPMC) exhibited an unexpected decrease in permeability and excellent one-dimensional swelling properties above a threshold in HPMC content. It is proposed that the observed material characteristics derive from the influence of HPMC on the aggregation behavior of MFC in such a way that above a critical HPMC content the films are created through self assembly into a layered structure, composed of low swelling layers with swellable inter layer regions. The suggested structures were supported by high resolution microscopy. The findings should hold potential for direct applications, but even more as a concept for future material design.
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