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Structure control by phase separation and influence on mass transport in films for controlled release

Helene Andersson (Institutionen för material- och tillverkningsteknik ; SuMo Biomaterials)
Göteborg : Chalmers University of Technology, 2015. ISBN: 978-91-7597-272-5.- 74 s.
[Doktorsavhandling]

Controlled release coatings for oral pharmaceutics are often made of cellulose derivatives. Such coatings can be used to promote a prolonged therapeutic concentration in the blood by a slow drug delivery in the gastrointestinal tract. Furthermore, two polymers with different solubilities can be used in the same coating to give the desirable release characteristics. If a water-soluble polymer is present in the film this polymer can leak out from the coating and form pores that mediate drug release. In this thesis, specific focus has been aimed at films made from the water-insoluble ethyl cellulose (EC) and the water-soluble hydroxypropyl cellulose (HPC). Although EC and HPC can be co-dissolved in ethanol they tend to phase-separate during the spray-coating process, which results in distinct domains enriched in one polymer and depleted in the other. Due to this, the HPC-rich phase can serve as a template for the pores. Since phase separation is affected by the physicochemical properties of the polymers, the microstructure is likely to be affected as well. This in turn could influence drug release. Therefore, structure control is important for controlled mass transport through the films. The major aim was to investigate how different molecular weight (Mw) grades of the two cellulose derivative affects the film microstructures and mass transport properties in order to better understand the structure-release relation. The EC/HPC films produced contained 30% w/w HPC using different Mw grades of either EC or HPC while keeping the other polymer fixed. In general, combined studies on both sprayed films, cast films and pellet coatings showed that the final structure can be shifted from a percolating bicontinuous structure to disconnected HPC-rich domains by use of different Mw grades. Disconnected domains will prevent extensive leakage of HPC and formation of pores, resulting in overall low film permeability. However, by the use of more rapid drying conditions this morphology can be changed to a more bicontinuous structure, which both increases the total polymer release and film permeability. On the other hand, when very rapid drying conditions are used, leading to an early arrest in phase separation and very small domains, this can also prevent HPC release and decrease the mass transfer rate through films. Decreasing film permeability was found for both freestanding sprayed films and pellet coatings with increasing Mw of EC. On the other hand, when different Mw grades of HPC were used, sprayed free films showed an optimum in water permeability in the middle Mw range and very low permeability for films with low Mw HPC. Moreover, a slow release rate of HPC was achieved by using a high Mw grade of HPC, which also caused a slow increase in permeability. The drug release behaviour from coated pellets was, however, very different. This was believed to be due to different manufacturing conditions for spraying of free films and pellet coatings, as well as differences in the evolution of the phase-separated structure for systems of EC/HPC with different Mw grades. Overall, it was concluded that the Mw grade used in the films affects the phase-separated structure and in turn the geometries and percolation of pores, which will influences the overall mass transport properties of film. In addition, the effect of manufacturing conditions will much depend on the Mw grades used. Therefore, combining the effects of the Mw and the manufacturing conditions can be useful as a tool for controlling structure formation and mass transport in films.

Nyckelord: Cellulose derivatives, Ethyl cellulose, Hydroxypropyl cellulose, Molecular weight, Polymer blend, Phase separation, Coating, Controlled release, Solvent evaporation



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Denna post skapades 2015-10-05. Senast ändrad 2016-03-22.
CPL Pubid: 223690