Design and development of polymeric nanoparticles by continuous manufacture using twin screw extrusion

The design spaces were predicted through Flory-Huggins (FH) based theory, and the selected ASDs were manufactured using extrusion to produce high-drug loaded ASDs (HDASDs). Secondly, the enhanced physical stability was further confirmed by high relative humidity (RH) (95% RH) storage stability studies as well as long term stability studies (40°C, 75% RH). Through this work, we have demonstrated that by implementing predictive thermodynamic modelling, ASD formulation design can be integrated into the extrusion process design to ensure the desired quality of the final dosage form. <br><br>This was the foundation for developing polymeric nanoparticles, the initial investigations focusing on one of ASD manufacture of NPX and EPO.

The initial feasibility study was conducted to confirm the plausibility of nanoparticle manufacture by TSE with a design of experiment (DoE) approach to highlight key process parameters. It was shown through this work that nanoparticles could be manufactured using extrusion. However, optimisation of process and formulation parameters was necessary for the nanoparticle formulations where there was poor nanoparticle recovery due to insufficient mixing.

The carrier selection, in particular the viscosity of three sugar alcohol carriers, xylitol (XYL), sorbitol (SORB) and erythritol (ERY), was assessed in addition to predicted required shear rates in order to produce homogenous mixtures of nanoparticles. Additionally, the ability to scale up the process was investigated with promising results. It was shown that the longer residence time achieved with, the larger extruder resulted in increased nanoparticle recovery and improved content uniformity.<br><br>We have shown that extrusion can be used to make reproducible nanoparticles in a continuous fashion.

Furthermore, we have shown from preliminary in vitro data that the nanoparticles can allow for controlled or targeted release based on the polymer selection. Further studies will focus on implementing this design to develop other nanoparticle systems and further in vivo analysis.