In vitro and in vivo evaluation of starch-based hot stage extruded double matrix systems.

The objective of developing a double matrix system consisting of a hot stage extruded starch pipe surrounding a hot stage extruded and drug-containing starch core, was to obtain a monolithic matrix system applicable in the domain of sustained drug release. The behaviour of the systems was evaluated through dissolution testing and through a randomised crossover bioavailability study on nine male volunteers. All double matrix systems showed in vitro a nearly constant drug release profile after an initial slower release phase of 4 h. This initial slower release phase was avoided by loading the starch pipe with a small amount of drug. The in vitro dissolution profiles did not reflect the in vivo behaviour of the systems. Although the in vitro dissolution profiles of two selected double matrix systems were slower than the profile of a commercially available sustained release formulation, they performed less well in vivo. However, the t75%Cmax ratios of the evaluated double matrix systems versus a reference immediate release formulation indicated an acceptable sustained release behaviour, superior to that of hot stage extruded starch-based single matrices. Therefore the disclosed drug delivery systems could be applied in the domain of sustained drug delivery. Besides, the continuous production of the double matrix systems offers an advantage from a manufacturing point of view.