title: Regulation of proxyphylline's release from silicone rubber matrices by the use of osmotically active excipients and a multi-layer system.
abstract: In this work we present results on the modification of the release kinetics of a water-soluble model drug (proxyphylline) from silicone rubber (SR) matrices by either: (i) the incorporation of inorganic salts acting as osmotically active excipients in single-layer matrices, containing a uniform concentration of proxyphylline or (ii) by the use of three-layer matrices with distributed proxyphylline load. In relation to (i) our data show that the incorporation of inorganic salts, of varying water solubilities and in different initial loads, accelerated the release of proxyphylline and helped to the stabilization of its declining release rate. Drug release kinetics is supplemented by measurements of concurrent water uptake, and salt release, kinetics. In addition, in order to further investigate the release mechanisms of the drug and the salts, we studied the diffusion and sorption properties of the depleted polymeric matrix along with the morphology and the mechanical properties of the matrices either in the presence or after the depletion of the solutes. The combined information, derived from these techniques, supports a drug release mechanism occurring through an excessively swollen polymer matrix and accelerated by the formation of microscopic cracks generated by the osmotically active excipients. In relation to (ii) we studied a multi-layer device with proxyphylline-loaded inner layer and drug-free outer layers which practically diminished the initial burst effect and allowed the release of about 60% of the drug at a constant rate.
authors.affiliation: Institute of Physical Chemistry, National Center for Scientific Research "Demokritos", 15310 Ag. Paraskevi Attikis, Athens, Greece. dsoulas@chem.demokritos.gr
authors.forename: Dimitrios N
authors.initials: DN
authors.lastname: Soulas
authors.forename: Kyriaki G
authors.initials: KG
authors.lastname: Papadokostaki
mesh_terms: D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D009995:Osmosis; D010316:Particle Size; D012492:Salts / Q000737:chemistry; D012826:Silicone Elastomers / Q000737:chemistry*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D005079:Excipients; D012492:Salts; D012826:Silicone Elastomers; C003237:proxyphylline; D013806:Theophylline