Abstract
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.
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.
| Original language | English |
|---|---|
| Pages (from-to) | 35-45 |
| Number of pages | 10 |
| Journal | International Journal of Pharmaceutics |
| Volume | 506 |
| Publication status | Published - 14 Apr 2016 |