Modeling, design and manufacture of innovative floating gastroretentive drug delivery systems based on hot-melt extruded tubes.

The problem of many gastroretentive systems is the mechanistic connection of drug release and gastric retention control. This connection could be successfully separated by formulating hollow tubes via hot-melt extrusion and sealing both tube ends, which led to immediately floating devices. The tube wall consisted of metformin crystals embedded in an inert polymer matrix of Eudragit® RS PO and E PO. Very high drug loadings of up to 80% (w/w) were used without generating a 'burst release'. Sustained release profiles from four to more than twelve hours were achieved by varying the polymer proportions without affecting the floatability. Buoyancy was found to mainly depend on the cylinder design, i.e. the outer to inner diameter ratio. This allowed the polymer/metformin composition to be changed without affecting buoyancy, i.e. a separation of floatability and release control was achieved. A prediction model was implemented that allowed for the buoyancy force to be determined with high accuracy by selecting a suitable ratio of outer to inner diameter of the modular tube die. Wall thickness and mass normalized surface area were identified as geometric parameters that mainly influenced the release properties. Conclusively, this study offers a highly flexible and rational manufacturing approach for the development of gastroretentive floating drug delivery systems.