A matrix-in-cylinder system for sustained drug delivery, consisting of a hot-melt extruded ethylcellulose (EC) pipe surrounding a drug containing HPMC-Gelucire 44/14 core, was evaluated in vitro and in vivo. In an aqueous medium, the HPMC-Gelucire core forms a gel plug, which releases the drug-through the open ends of the EC pipe--by means of erosion. The influence of hydrodynamic and mechanical stress and the effect of different 'physiologically relevant' dissolution media on the in vitro drug release were investigated. From these in vitro dissolution tests, it was concluded that the EC pipe has a protective effect on the drug containing HPMC-Gelucire core. It largely protects the core against hydrodynamics and mechanical stress. Furthermore, drug release from the matrix-in-cylinder system was only slightly affected by the composition of the dissolution medium. A randomised crossover in vivo study in dogs revealed that the matrix-in-cylinder system containing propranolol hydrochloride has an ideal sustained release profile with constant plasma levels maintained over 24 h. Moreover, administration of the matrix-in-cylinder system resulted in a 4-fold increase in propranolol bioavailability when compared with a commercial sustained release formulation (Inderal).