Residence time modeling of hot melt extrusion processes.

The hot melt extrusion process is a widespread technique to mix viscous melts. The residence time of material in the process frequently determines the product properties. An experimental setup and a corresponding mathematical model were developed to evaluate residence time and residence time distribution in twin screw extrusion processes. The extrusion process was modeled as the convolution of a mass transport process described by a Gaussian probability function, and a mixing process represented by an exponential function. The residence time of the extrusion process was determined by introducing a tracer at the extruder inlet and measuring the tracer concentration at the die. These concentrations were fitted to the residence time model, and an adequate correlation was found. Different parameters were derived to characterize the extrusion process including the dead time, the apparent mixing volume, and a transport related axial mixing. A 2(3) design of experiments was performed to evaluate the effect of powder feed rate, screw speed, and melt viscosity of the material on the residence time. All three parameters affect the residence time of material in the extruder. In conclusion, a residence time model was developed to interpret experimental data and to get insights into the hot melt extrusion process.

Solid crystal suspensions containing griseofulvin--preparation and bioavailability testing.

The improvement of the bioavailability of poorly soluble drugs has been an important issue in pharmaceutical research for many years. Despite the suggestion of several other technologies in the past, drug particle size reduction is still an appropriate strategy to guarantee high bioavailability of various drugs. A few years ago, the Solid Crystal Suspension (SCS) technology was suggested, in which crystalline drug particles are ground and dispersed in a highly soluble crystalline carrier by a hot melt extrusion process. The current study demonstrates the scale-up of the SCS technology to standard, lab-scale extrusion equipment--a change from previous investigations, which used small batch sizes. A twin-screw extruder was modified to account for the rapid crystallization of the carrier. The screw speed and the barrel temperature were identified as critical process parameters and were varied systematically in several experimental designs. Finally, parameters were identified that produced extrudates with rapid dissolution rates. After extrusion, the extrudates were milled to granules and then tableted. These tablets were investigated with respect to their bioavailability in beagle dogs. It was found that drug particle size reduction in the hot melt extrusion led to 3.5-fold higher bioavailability in these dogs than occurred with the physical mixture of the used substances. The solid crystal suspension formulation had a slightly higher bioavailability than the marked product. In conclusion, the SCS technology was successfully scaled up to lab-scale equipment, and the concept was confirmed by a bioavailability study.