| 1. |
- 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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| 2. |
- Caccavo, D., et al.
(författare)
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Effects of HPMC substituent pattern on water up-take, polymer and drug release: An experimental and modelling study
- 2017
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 528:1-2, s. 705-713
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick's law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices.
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