NANEX: Process design and optimization

Previously, we introduced a one-step nano-extrusion (NANEX) process for transferring aqueous nanosuspensions into solid formulations directly in the liquid phase. Nano-suspensions were fed into molten polymers via a side-feeding device and excess water was eliminated via devolatilization. However, the drug content in nano-suspensions is restricted to 30 % (w/w), and obtaining sufficiently high drug
loadings in the final formulation requires the processing of high water amounts and thus a fundamental process understanding. To this end, we investigated four polymers with different physicochemical characteristics (Kollidon1 VA64, Eudragit1 E PO, HPMCAS and PEG 20000) in terms of their maximum water uptake/removal capacity. Process parameters as throughput and screw speed were adapted and
their effect on the mean residence time and filling degree was studied. Additionally, one-dimensional discretization modeling was performed to examine the complex interactions between the screw geometry and the process parameters during water addition/removal. It was established that polymers
with a certain water miscibility/solubility can be manufactured via NANEX. Long residence times of the molten polymer in the extruder and low
filling degrees in the degassing zone favored the addition/
removal of significant amounts of water. The residual moisture content in the
final extrudates was comparable to that of extrudates manufactured without water.