title: The effect of polymer properties on direct compression and drug release from water-insoluble controlled release matrix tablets.
abstract: The objective of this study was to identify and evaluate key polymer properties affecting direct compression and drug release from water-insoluble matrices. Commonly used polymers, such as Kollidon(®) SR, Eudragit(®) RS and ethyl cellulose, were characterized, formulated into tablets and compared with regard to their properties in dry and wet state. A similar site percolation threshold of 65% v/v was found for all polymers in dry state. Key parameters influencing polymer compactibility were the surface properties and the glass transition temperature (T(g)), affecting polymer elasticity and particle size-dependent binding. The important properties observed in dry state also governed matrix characteristics and therefore drug release in wet state. A low T(g) (Kollidon(®) SR<Eudragit(®) RS) decreased the percolation threshold, particle size effect and tortuosity, but increased permeability and sensitivity to heat/humidity treatment. Hence, lower permeability and higher stability are benefits of a high-T(g) polymer (ethyl cellulose). However, release retardation was observed in the same order as matrix integrity (Eudragit(®) RS<ethyl cellulose<Kollidon(®) SR), as the high permeability was counteracted by PVP in case of Kollidon(®) SR. Therefore, the Tg and composition of a polymer need to be considered in polymer design and formulation of controlled-release matrix systems.
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, Berlin 12169, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Grund
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, Berlin 12169, Germany. Electronic address: koerberm@zedat.fu-berlin.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Koerber
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, Berlin 12169, Germany.
authors.forename: Mathias
authors.initials: M
authors.lastname: Walther
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, Berlin 12169, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Bodmeier
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D019245:Compressive Strength; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004400:Dyphylline / Q000737:chemistry*; D004548:Elasticity; D006358:Hot Temperature; D006813:Humidity; D007700:Kinetics; D010316:Particle Size; D010539:Permeability; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D044366:Transition Temperature; D014867:Water / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011108:Polymers; D013607:Tablets; D014867:Water; D004400:Dyphylline; C050528:Eudragit RS; C013517:ethyl cellulose; D002482:Cellulose; D011205:Povidone
keywords: Controlled release; Diprophylline (PubChem CID: 3182); Direct compression; Ethocel(®) Std. (PubChem CID: 24832091); Eudragit(®) RS (PubChem CID: 104931); Fumed silica (PubChem CID: 24261); Glass transition temperature; Magnesium stearate (PubChem CID: 11177); Matrix tablet; Percolation threshold; Polyvinyl pyrrolidone (PubChem CID: 6917); Water-insoluble polymers