Mass Transport through Phase Separated Films - Effects of Ethyl Cellulose Molecular Weight on Cellulose Derivative Blends for Pharmaceutical Coatings

Detta är en avhandling från Chalmers University of Technology

Sammanfattning: Polymer blends are utilized for a variety of applications, not least in pharmaceutical coatings for controlled release of drugs. For instance, blends of ethyl cellulose (EC) and the water-soluble hydroxypropyl cellulose (HPC) can be used to coat drug pellets for oral extended release formulations. Although EC and HPC can be co-dissolved in ethanol, they tend to phase separate during solvent evaporation in the coating process. If a substantial amount of HPC is present in the coating, pores form when the coating is subjected to water. The HPC-rich phase may then serve as a template for the pore geometries that transport the drug. Phase separated microstructures can have a variety of morphological features. However, polymer phase separation is a complex process and much is still left to be understood regarding the underlying mechanisms that drive structure evolution. A range of physical and chemical parameters are known to affect phase separation, including the molecular weight (MW) of polymers. If the morphology of phase separated structures is affected by the MW, then drug release through a phase separated coating is likely to be affected as well. The major aims of this work were to study the effects of the MW of EC, on the mass transport and microstructure in films made of 70% EC and 30% HPC, and to understand the underlying mechanisms behind different release profiles from coated pharmaceutical pellets. A wide range of batches of EC were investigated, with weight average MWs from 19·10^3 to 68·10^3. Overall, the effects on solvent cast films, sprayed films and spray coated pellets were investigated. The MW showed substantial influence on the phase separated morphology, as well as effects on the pore structures in sprayed freestanding films. A decrease in mass transfer rate with increasing MW of EC was found by permeability measurements on free films and drug release from coated pellets. The observed trend in permeability was mainly affected by the geometries of pores, while drug release was affected by both HPC-leakage and the film structure. As a result, it was concluded that the MW of EC affects the phase separated structure of EC/HPC-films, which has profound effects on diffusion mediated release from coated pellets.

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