| 1. |
- Carmona, Pierre, 1995, et al.
(författare)
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Controlling the structure of spin-coated multilayer ethylcellulose/ hydroxypropylcellulose films for drug release
- 2023
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Ingår i: International Journal of Pharmaceutics. - 0378-5173 .- 1873-3476. ; 644
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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. Water-soluble HPC leaches out and forms a porous structure that controls the drug transport. Industrially, the pellets are coated using a fluidized bed spraying device, and a layered film exhibiting varying porosity and structure after leaching is obtained. A detailed understanding of the formation of the multilayered, phase-separated structure during production is lacking. Here, we have investigated multilayered EC/HPC films produced by sequential spin-coating, which was used to mimic the industrial process. The effects of EC/HPC ratio and spin speed on the multilayer film formation and structure were investigated using advanced microscopy techniques and image analysis. Cahn-Hilliard simulations were performed to analyze the mixing behavior. A gradient with larger structures close to the substrate surface and smaller structures close to the air surface was formed due to coarsening of the layers already coated during successive deposition cycles. The porosity of the multilayer film was found to vary with both EC/HPC ratio and spin speed. Simulation of the mixing behavior and in situ characterization of the structure evolution showed that the origin of the discontinuities and multilayer structure can be explained by the non-mixing of the layers.
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| 2. |
- 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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| 3. |
- Carmona, Pierre, 1995, et al.
(författare)
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Glyceraldehyde as an efficient chemical crosslinker agent for the formation of chitosan hydrogels
- 2021
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Ingår i: Gels. - : MDPI AG. - 2310-2861. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- The rheological changes that occur during the chemical gelation of semidilute solutions of chitosan in the presence of the low‐toxicity agent glyceraldehyde (GCA) are presented and discussed in detail. The entanglement concentration for chitosan solutions was found to be approximately 0.2 wt.% and the rheological experiments were carried out on 1 wt.% chitosan solutions with various amounts of GCA at different temperatures (25 °C and 40 °C) and pH values (4.8 and 5.8). High crosslinker concentration, as well as elevated temperature and pH close to the pKa value (pH ≈ 6.3–7) of chitosan are three parameters that all accelerate the gelation process. These conditions also promote a faster solid‐like response of the gel‐network in the post‐gel region after long curing times. The mesh size of the gel‐network after a very long (18 h) curing time was found to contract with increasing level of crosslinker addition and elevated temperature. The gelation of chitosan in the presence of other chemical crosslinker agents (glutaraldehyde and genipin) is discussed and a comparison with GCA is made. Small angle neutron scattering (SANS) results reveal structural changes between chitosan solutions, incipient gels, and mature gels.
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| 4. |
- 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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| 5. |
- Carmona, Pierre, 1995
(författare)
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Structure evolution of phase-separated EC/HPC films for controlled drug release
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Porous phase-separated ethylcellulose/hydroxypropylcellulose (EC/HPC) films are used to control drug transport out of pharmaceutical pellets. The drug transport rate is determined by the structure of the porous films that are formed as the water-soluble HPC leaches out. In industry, the pellets are being coated using a fluidized bed spraying device, and layered films with varying porosity and structure are obtained. A detailed understanding of the formation mechanisms of the multilayered phase-separated structure during production is lacking. Here, we have investigated EC/HPC films produced by spin-coating, which mimics the industrial manufacturing process in a reproducible and well-controlled manner. This work is aimed to understand why the film structure is layered, and why it exhibits different porosities and structures by understanding the film formation mechanisms. The 2D and 3D structures of the EC/HPC films were characterized using confocal laser scanning microscopy (CLSM), scanning electron microscopy (SEM), focused ion beam SEM (FIB-SEM) and image analysis. The thickness of the films was measured by profilometry. To be able to understand the multilayer formation, we first studied the structure evolution in EC/HPC monolayer films. The effect of the EC/HPC ratio (from 15 to 85 wt% HPC) on the in-plane and cross-sectional structure evolution was determined. Bicontinuous structures were found for 30 to 40 wt% HPC and discontinuous structures were found for the fractions 15 to 22 and 45 to 85 wt% HPC. The growth of the characteristic length scale followed a power law, , with for bicontinuous structures, and 0.45 - 0.75 for discontinuous structures. An image analysis method to characterize the time-dependent 2D curvature evolution was developed. Two main coarsening mechanisms could be identified: interfacial tension-driven hydrodynamic growth for bicontinuous structures and diffusion-driven coalescence for discontinuous structures. The cross-sectional structure evolution shows that during shrinkage of the film, the phase-separated structure undergoes a transition from 3D to nearly 2D structure evolution along the surface. The shrinkage rate was found to be independent of the EC/HPC ratio. A new method to estimate part of the binodal curve in the ternary phase diagram for EC/HPC in ethanol has been developed. For multilayer films, the results showed that the inherent behaviour of the monolayer films have a strong impact on the formation of each new layer in multilayer films. A gradient in structure size with larger structures close to the substrate and smaller structures close to the air surface was found and explained by the redissolution of the layers already deposited during previous deposition cycles. By varying the EC/HPC ratio during the multilayer film production, we showed in situ that the layers do not mix. By varying the spin speed every other layer, we produced a layered film exhibiting varying porosity, proposing a possible explanation for obtaining a layered coating in the industrial process. The findings of this work provide a good understanding of the mechanisms responsible for the morphology development and enable tailoring of multilayer EC/HPC films structure for controlled drug release.
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| 6. |
- Carmona, Pierre, 1995
(författare)
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Structure evolution of spin-coated phase separated EC/HPC films
- 2021
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)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 liquid in the stomach or intestine. However, detailed understanding of the structure evolution is lacking. In this work, we use spin-coating, a widely applied technique for making thin uniform polymer films, to mimic the industrial manufacturing process of fluidized bed spraying. The aim of this work is to understand the structure evolution and phase separation kinetics of single layer and multi-layer spin-coated EC/HPC films. The structure evolution is characterized using confocal laser scanning microscopy (CLSM) and image analysis. The influence of spin-coating parameters and EC:HPC ratio on the final phase-separated structure and the film thickness was determined. Varying spin speed and EC:HPC ratio gave us precise control over the characteristic length scale and thickness of the film. The results show that the phase separation occurs through spinodal decomposition and 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. Furthermore, optimized spin-coating parameters were selected to study the kinetics of phase separation in situ, in particular the coarsening mechanisms and the time dependence of the domain’s growth as a function of EC:HPC ratio. We identified two main coarsening mechanisms: interfacial tension driven hydrodynamic growth for the bicontinuous structure and diffusion driven coalescence for the discontinuous structures. In addition, we obtained information on the wetting, the shrinkage, and the evaporation process by looking at a film cross section, which allowed an estimation of the binodal of the phase diagram. The findings from this work give a good understanding of the mechanisms responsible for the morphology development and open the road towards tailoring thin EC/HPC film structures for controlled drug release.
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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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