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Ethyl Cellulose Membranes used in Modified Release Formulations

Johan Hjärtstam (Institutionen för polymerteknologi)
Göteborg : Chalmers University of Technology, 1998. ISBN: 91-7197-619-1.

Ethyl cellulose (EC) is a commonly used polymer in modified drug release formulations. The general aim of the present study was to investigate release mechanisms through non-porous EC membranes with hydroxypropyl methyl cellulose (HPMC) contents ranging from 0 to 30% by weight. Experiments on free films and coated drug particles reveal that the drug release is governed by an osmotic pump mechanism for EC membranes with an HPMC content up to 24 wt%. In a novel pressurized cell, it was found that, to make the film permeable to potassium chloride (model substance), it must be submitted to a stress provided by a hydrostatic pressure in the core. Water is imbibed by osmosis and produces the tensile stress. Furthermore, when examining drug pellets it was concluded that the hydrostatic pressure in the core caused a volume increase. As soon as the release began, the volume expansion ended. It is suggested that the tensile stress produces small alterations, microvoids, in the membrane which affect the transport properties of the coating. Increasing the HPMC content in the film lowered the magnitude of the applied tensile stress required to induce permeability. When the amount of HPMC exceeded 24 wt%, the leaching of the water-soluble polymer was significant. This re-sulted in pore formation, which increased the diffusive release of the drug.

The knowledge gained on EC membranes produced by a phase separation technique, using ethanol and water, reveals that water permeability and the release rate profiles are drastically changed by an increase of the non-solvent in the liquid-liquid demixing process.

Finally, a study is presented in which the hydroxyl group content in the EC chain lies between 2.76 and 3.11 wt%. The results indicate that the modulus of elasticity of a free film decreases as the hydroxyl group content increases. This is thought to be due to the lower solubility of EC with a lower degree of substitution, as determined by the Huggins interaction constant in the film- forming solution, and the ability of the film with a high hydroxyl group content to hold more water. A study on spray-coated pellets was performed and revealed that the release rate is higher in EC with a lower degree of substitution. This observation is in agreement with water permeability measurements on free films.

Nyckelord: ethyl cellulose, drug release, osmotic pumping, reflectivity, degree of substitution, water permeability, mechanical strength

Denna post skapades 2006-08-28. Senast ändrad 2013-09-25.
CPL Pubid: 947


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