Water-insoluble polymers as binders for controlled release matrix and reservoir pellets

The typical manufacturing procedure of controlled release pellets includes preparation of drug cores using water-soluble binders, followed by coating with release-controlling polymers. The main objective of this work was to investigate the applicability of water-insoluble polymers, usually used for coating, as binders for pellets preparation as an alternative formulation tool to control the drug release. The use of water-insoluble polymers as binders instead of the water-soluble ones for pellets preparation was an effective tool to control the drug release. With poorly soluble drugs, extended and enteric release profiles were achieved without an additional polymer coating, in contrast to an immediate release from pellets prepared with water-soluble binders. The release retardation efficiency was in the order of Ethocel® > Eudragit® RS 100 > Kollidon® SR when used as organic solutions, and, Eudragit® NE 30 D > Kollicoat® SR 30 D ≈ Eudragit® RS 30 D > Aquacoat® ECD as aqueous polymer dispersions. Upon pellets tabletting, the acrylate-based polymers (Eudragit®) were more resistant than ethylcellulose-based (Ethocel®/ Aquacoat® ECD) reflected by the increase in drug release upon compression. Drug release from pellets prepared with the flexible polyvinyl acetate-based polymers (Kollidon® SR/ Kollicoat® SR 30 D) was not affected by compression. For the higher soluble drugs, much less polymer coating was required to retard the drug release when the water-insoluble polymers were used as binders compared to water-soluble ones. Because of the several advantages of matrix systems, the higher soluble drugs were additionally formulated into controlled release matrix-layered pellets by layering with high amounts of Ethocel® or Kollicoat® SR 30 D. The required amount of polymer was highly dependent on drug solubility, the higher the drug solubility, the more polymer was required to control the release. Drug release decreased by increasing the drug loading (layering thickness) because of a decreased surface area/dose ratio and increased diffusion path length. Regarding the release adjustment of drug combinations from multilayer matrix-pellets, the drugs with higher solubility were layered first onto the cores and the less soluble ones were layered on top. The release of higher soluble drug (first drug) was delayed and slower compared to the less soluble drug (second drug). By addition of a pore-former to the top drug layer, the release of both drugs increased, with a higher extent for the first drug. Similar release of both drugs could be achieved by an appropriate selection of the amount of ethylcellulose in each drug layer and the ratio of the pore-former in the second drug layer.

Author dc:creator

• Zoubari, Mohammad Gaith

• Water-insoluble binders
• controlled release pellets
• Extrusion/spheronization
• Drug layering

Licence dc:rights.uri

• http://www.fu-berlin.de/sites/refubium/rechtliches/Nutzungsbedingungen

Language dc:language

eng, ger

Identifier URI

http://dx.doi.org/10.17169/refubium-10092

OAI record oai:identifier

https://refubium.fu-berlin.de/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Arefubium.fu-berlin.de%3Afub188%2F5893