Water-insoluble polymers as binders for pellet drug layering: Effect on drug release and performance upon compression

摘要

The objective of this study was to investigate the applicability of water-insoluble polymers as binders for pellet drug layering to extend the drug release. Carbamazepine was layered on sugar cores in fluidized bed coater using isopropanol (IPA):water solution or aqueous dispersion of ethylcellulose, polyvinyl acetate or ammonium-methylmethacrylate copolymer. Carbamazepine release was extended with all investigated water-insoluble polymers used as binder, without an additional coating layer. Drug release from pellets layered using IPA:water polymer solutions was dependent on polymer properties such as lipophilicity and pore-forming components, while from those layered with aqueous polymer dispersions, the release was dependent on the completeness of film formation during drug layering. Curing effect was observed only for pellets layered with Aquacoat (R) ECD and Eudragit (R) RS 30D. The drug release was not affected by compression when pellets were prepared with the flexible polymers Kollidon (R) SR or Kollicoat (R) SR 30D, however, it increased when brittle polymers such as ethylcellulose or Eudragit (R) RS were used. This problem could be minimized by using a higher amount of the binder, addition of a plasticizer or using polymers of higher viscosity grade. In conclusion, the use of water-insoluble polymers as binder for pellet drug layering is an effective tool to extend the drug release without additional coating step.