| 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, et al.
(författare)
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Effects of Molecular Weight on Phase Separated Coatings for Controlled Release of Drugs
- 2013
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Ingår i: Annual Transactions of the Nordic Rheology Society. ; , s. 249-
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Tidskriftsartikel (refereegranskat)abstract
- Phase separated films with controlled porosity were made from ethyl cellulose (EC) and 30% w/w hydroxypropyl cellulose (HPC). The molecular weight of EC can be used to modify the mass transfer rate through coatings by effects on microstructure of the film. Processing conditions are, however, affected by the solution rheology, which could influence the film quality when using different molecular weights.
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| 3. |
- 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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| 4. |
- Carlert, Sara, et al.
(författare)
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Predicting intestinal precipitation : a case example for a basic BCS class II drug
- 2010
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Ingår i: Pharmaceutical research. - : Springer Science and Business Media LLC. - 0724-8741 .- 1573-904X. ; 27:10, s. 2119-2130
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To investigate the prediction accuracy of in vitro and in vitro/in silico methods for in vivo intestinal precipitation of basic BCS class II drugs in humans. METHODS: Precipitation rate of a model drug substance, AZD0865 (pKa = 6.1; log K(D) = 4.2), was investigated in vitro using simulated intestinal media, and calculations of the crystallization rates were made with a theoretical model. Human intestinal precipitation was estimated by analysis of pharmacokinetic data from clinical studies at different doses. RESULTS: All in vitro models predicted rapid drug precipitation, where the intestinal concentration of dissolved AZD0865 at the highest dose tested was expected to decrease to half after less than 20 min. However, there was no indication of precipitation in vivo in humans as there was a dose proportional increase in drug plasma exposure. The theoretical model predicted no significant precipitation within the range of expected in vivo intestinal concentrations. CONCLUSIONS: This study indicated that simple in vitro methods of in vivo precipitation of orally administered bases overpredict the intestinal crystalline precipitation in vivo in humans. Hydrodynamic conditions were identified as one important factor that needs to be better addressed in future in vivo predictive methods.
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| 5. |
- Carmona, Pierre, 1995, et al.
(författare)
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Cross-sectional structure evolution of phase-separated spin-coated ethylcellulose/hydroxypropylcellulose films during solvent quenching
- 2022
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Ingår i: RSC Advances. - : Royal Society of Chemistry. - 2046-2069. ; 12:40, s. 26078-26089
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Tidskriftsartikel (refereegranskat)abstract
- Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. The films are applied on the pellets using fluidized bed spraying. The drug transport rate is determined by the structure of the porous films that are formed as the water-soluble HPC leaches out. However, a detailed understanding of the evolution of the phase-separated structure during production is lacking. Here, we have investigated EC/HPC films produced by spin-coating, which mimics the industrial manufacturing process. This work aimed to understand the structure formation and film shrinkage during solvent evaporation. The cross-sectional structure evolution was characterized using confocal laser scanning microscopy (CLSM), profilometry and image analysis. The effect of the EC/HPC ratio on the cross-sectional structure evolution was investigated. During shrinkage of the film, the phase-separated structure undergoes a transition from 3D to nearly 2D structure evolution along the surface. This transition appears when the typical length scale of the phase-separated structure is on the order of the thickness of the film. This was particularly pronounced for the bicontinuous systems. The shrinkage rate was found to be independent of the EC/HPC ratio, while the initial and final film thickness increased with increasing HPC fraction. A new method to estimate part of the binodal curve in the ternary phase diagram for EC/HPC in ethanol has been developed. The findings of this work provide a good understanding of the mechanisms responsible for the morphology development and allow tailoring of thin EC/HPC films structure for controlled drug release.
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| 6. |
- Carmona, Pierre, 1995, et al.
(författare)
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Structure evolution during phase separation in spin-coated ethylcellulose/hydroxypropylcellulose films
- 2021
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Ingår i: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 17:14, s. 3913-3922
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Tidskriftsartikel (refereegranskat)abstract
- Porous phase-separated films made of ethylcellulose (EC) and hydroxypropylcellulose (HPC) are commonly used for controlled drug release. The structure of these thin films is controlling the drug transport from the core to the surrounding liquids in the stomach or intestine. However, detailed understanding of the time evolution of these porous structures as they are formed remains elusive. In this work, spin-coating, a widely applied technique for making thin uniform polymer films, was used to mimic the industrial manufacturing process. The focus of this work was on understanding the structure evolution of phase-separated spin-coated EC/HPC films. The structure evolution was determined using confocal laser scanning microscopy (CLSM) and image analysis. In particular, we determined the influence of spin-coating parameters and EC : HPC ratio on the final phase-separated structure and the film thickness. The film thickness was determined by profilometry and it influences the ethanol solvent evaporation rate and thereby the phase separation kinetics. The spin speed was varied between 1000 and 10 000 rpm and the ratio of EC : HPC in the polymer blend was varied between 78 : 22 wt% and 40 : 60 wt%. The obtained CLSM micrographs showed phase separated structures, typical for the spinodal decomposition phase separation mechanism. By using confocal laser scanning microscopy combined with Fourier image analysis, we could extract the characteristic length scale of the phase-separated final structure. Varying spin speed and EC : HPC ratio gave us precise control over the characteristic length scale and the thickness of the film. The results showed that the characteristic length scale increases with decreasing spin speed and with increasing HPC ratio. The thickness of the spin-coated film decreases with increasing spin speed. It was found that the relation between film thickness and spin speed followed the Meyerhofer equation with an exponent close to 0.5. Furthermore, good correlations between thickness and spin speed were found for the compositions 22 wt% HPC, 30 wt% HPC and 45 wt% HPC. These findings give a good basis for understanding the mechanisms responsible for the morphology development and increase the possibilities to tailor thin EC/HPC film structures.
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| 7. |
- Carmona, Pierre, 1995, et al.
(författare)
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Structure formation and coarsening kinetics of phase-separated spin-coated ethylcellulose/hydroxypropylcellulose films
- 2022
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Ingår i: Soft Matter. - : Royal Society of Chemistry. - 1744-683X .- 1744-6848. ; 18:16, s. 3206-3217
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Tidskriftsartikel (refereegranskat)abstract
- Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport from pharmaceutical pellets. The drug transport rate is determined by the structure of the porous films that are formed as water-soluble HPC leaches out. However, a detailed understanding of the evolution of the phase-separated structure in the films is lacking. In this work, we have investigated EC/HPC films produced by spin-coating, mimicking the industrial fluidized bed spraying. The aim was to investigate film structure evolution and coarsening kinetics during solvent evaporation. The structure evolution was characterized using confocal laser scanning microscopy and image analysis. The effect of the EC:HPC ratio (15 to 85 wt% HPC) on the structure evolution was determined. Bicontinuous structures were found for 30 to 40 wt% HPC. The growth of the characteristic length scale followed a power law, L(t) ∼ t(n), with n ∼ 1 for bicontinuous structures, and n ∼ 0.45-0.75 for discontinuous structures. The characteristic length scale after kinetic trapping ranged between 3.0 and 6.0 μm for bicontinuous and between 0.6 and 1.6 μm for discontinuous structures. Two main coarsening mechanisms could be identified: interfacial tension-driven hydrodynamic growth for bicontinuous structures and diffusion-driven coalescence for discontinuous structures. The 2D in-plane interface curvature analysis showed that the mean curvature decreased as a function of time for bicontinuous structures, confirming that interfacial tension is driving the growth. The findings of this work provide a good understanding of the mechanisms responsible for morphology development and open for further tailoring of thin EC/HPC film structures for controlled drug release. © 2022 The Royal Society of Chemistry
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| 8. |
- Eriksson Barman, Sandra, 1985, et al.
(författare)
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New characterization measures of pore shape and connectivity applied to coatings used for controlled drug release
- 2021
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 1520-6017 .- 0022-3549. ; 110:7, s. 2753-2764
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Tidskriftsartikel (refereegranskat)abstract
- Pore geometry characterization-methods are important tools for understanding how pore structure influences properties such as transport through a porous material. Bottlenecks can have a large influence on transport and related properties. However, existing methods only catch certain types of bottleneck effects caused by variations in pore size. We here introduce a new measure, geodesic channel strength, which captures a different type of bottleneck effect caused by many paths coinciding in the same pore. We further develop new variants of pore size measures and propose a new way of visualizing 3-D characterization results using layered images. The new measures together with existing measures were used to characterize and visualize properties of 3-D FIB-SEM images of three leached ethyl-cellulose/hydroxypropyl-cellulose films. All films were shown to be anisotropic, and the strongest anisotropy was found in the film with lowest porosity. This film had very tortuous paths and strong geodesic channel-bottlenecks, while the paths through the other two films were relatively straight with well-connected pore networks. The geodesic channel strength was shown to give important new visual and quantitative insights about connectivity, and the new pore size measures provided useful information about anisotropies and inhomogeneities in the pore structures. The methods have been implemented in the freely available software MIST.
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| 9. |
- 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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| 10. |
- Kjaer Jepsen, Philip, 1995, et al.
(författare)
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Wurster fluidised-bed coating: Coarse-graining technique within CFD-DEM in conjunction with heat and mass transfer
- 2024
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Ingår i: Powder Technology. - 1873-328X .- 0032-5910. ; 443
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Tidskriftsartikel (refereegranskat)abstract
- In this study, we use a combined CFD-Discrete Element Method to assess predictive capabilities and numerical implications of a coarse-graining technique in Wurster fluidised-bed coaters. We investigated both hydrodynamics and heat and mass transfer and conducted simulations of a full three-phase system for the original and three coarse-grained systems, analysing velocity distributions, macroscopic solid stresses, moisture content and phase temperatures. We achieved a logarithmic simulation speed-up by aggregating up to 64 original particles into each coarse grain. This was accomplished while maintaining fidelity to the original CFD-DEM system in terms of reproducing with high accuracy macroscopic granular flow properties in different regions of a coater (drying, tube and bed regions). By integrating a liquid spray and humid air, we demonstrated that the phase temperatures were accurately predicted within the coarse-grained system, with a high capability of delivering liquid spray distributions with the same uniformity and drying. We also give arguments for choosing a certain degree of coarse-graining as a compromise between a desired reduction of computational costs and a trustworthy reproduction of granular-flow physics encountered in different regions of a Wurster bed. Our findings pave the way to using CFD-DEM to industrially-scaled Wurster-bed systems, which is currently unfeasible due to prohibitive computational costs.
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