For the simulation of liquid sloshing, particle simulation methods allow a detailed investigation of the acting dynamics. Since these methods usually go along with considerable computational loads the application of alternative, simplified models is a usual proceeding. However, the parameters of the simplified model can not be directly computed from physical quantities in the general case, such that parameter identification based on measurements is required. In applications where experimental investigation is expensive, the use of particle simulation results for parameter identification can be a promising alternative. This contribution considers the identification of the parameters of a simplified model for different container geometries and filling levels based on smoothed particle hydrodynamics (SPH) simulation results. The comparison with experimental data verifies the accuracy and sensitivity of both the used particle model as well as the simplified model.

Liquid sloshing is a free surface flow phenomenon with particular impact in applications such as dynamics of vehicles, ships or aircrafts (e.g. sloshing in tanks), solutions for vibration damping (e.g. tuned liquid mass dampers), as well as in industrial automation and robotic systems (e.g. handling of liquid-filled vessels). Whether sloshing effects are utilized to reduce vibrations or, on the contrary, introduce disturbing forces to the system, the understanding of the liquid sloshing dynamics is crucial to obtain the respective desired system behavior. To this end, due to the complex dynamic effects, numerical methods are vital means for analysis and optimization. In the present work, we focus on the transport and handling of liquid-filled containers in the context of robotics and automation, analyzed using the method Smoothed Particle Hydrodynamics (SPH). The properties and potential of the chosen numerical approach are investigated and evaluated by examples from literature, and several extensions over conventional SPH implementations are proposed in order to enhance accuracy and robustness.

Due to its meshless nature, the smoothed particle hydrodynamics method (SPH) provides high potential for the simulation of free‐surface flows and mixing in complex geometries. We used SPH to analyze the flow inside five typical screw elements of corotating twin‐screw extruders, two conveying elements, two kneading elements and a mixing element. Our results show conveying capabilities, pressure generation and power input for various operation states, completely and partially filled. We conducted a detailed mixing analysis based on tracer particles, which yielded the time evolution of the intensity of segregation for different tracers. From that, we determined exponential mixing rates, which describe the relative decrease of the intensity of segregation per screw revolution and characterize the mixing performance in different operation states. This provides valuable input information for simplified models of extruders, which are relevant to industrial applications and can significantly contribute to the efficient design, optimization and scale‐up of extruders. © 2017 American Institute of Chemical Engineers AIChE J, 63: 2451–2463, 2017

A novel approach for the simulation of the flow in co-rotating twin-screw extruders based on smoothed particle hydrodynamics (SPH) was presented in Part 1. Specifically, we showed detailed results for the flow field in a completely filled conveying element, which are in excellent agreement with data from the literature obtained with computational fluid dynamics (CFD). Moreover, we studied the flow in the partially filled conveying element, facilitated by the inherent capabilities of SPH for modeling free-surface flows. In Part 2, we show a detailed analysis of the mixing effects based on the presented SPH simulations. We studied the mixing using tracer particles for the completely and partially filled states, evaluated the time evolution of the intensity of segregation and fitted kinetic laws in order to determine mixing rates. We conducted this separately for overall mixing and axial mixing and analyzed the contributions of axial and cross mixing to the overall mixing rates. We showed these results for various operation states and finally, presented a case study highlighting the effect of the residence time on mixing together with the determined mixing rates per screw revolution. This confirms that SPH is a very promising tool for the investigation of mixing in complex geometries in both, completely filled and partially filled states. The presented results provide an excellent basis for the further improvement of simplified models of entire extrusion processes, including a quantification of mixing.

Due to the complex geometry of the rotating screws and, typically, free surface flows in partially filled screw sections, first principles simulations of the flow in co-rotating intermeshing twin-screw extruders using the well-established, mesh-based CFD (computational fluid dynamics) approaches are highly challenging. These issues can be resolved via the smoothed particle hydrodynamics (SPH) method thanks to its meshless nature and the inherent capability to simulate free surface flows. In our previous work, we developed a novel method for modeling the boundary conditions with complex wall geometries, under which SPH could be efficiently applied to complex surfaces of typical screw geometries of extruders. In this work, we employed SPH and our boundary method to study the flow in a conveying element in detail. To address unresolved clearances, we developed a new model that is coupled to SPH and can correctly account for the flow through unresolved clearances. A validation of our approach using CFD data from the literature for a completely filled conveying element indicated excellent agreement. Consequently, we studied the flow in a partially filled conveying element and obtained results for the flow rate, the power input and the axial force with variable filling ratio. A detailed analysis of the corresponding mixing phenomena is presented in Part 2. Our results show that the proposed method is a comprehensive approach to study the flow in different types of screw elements in detail, providing an excellent basis for further development of simplified models of entire extrusion processes.

Since more than 40% of today's drugs have low stability, poor solubility and/or limited ability to cross certain biological barriers, new platform technologies are required to address these challenges. This paper describes a novel continuous process that converts a stabilized aqueous nano-suspension into a solid oral formulation in a single step (i.e., the NANEX process) in order to improve the solubility of a model drug (phenytoin). Phenytoin nano-suspensions were prepared via media milling using different stabilizers. A stable nano-suspension was obtained using Tween(®) 80 as a stabilizer. The matrix material (Soluplus(®)) was gravimetrically fed into the hot melt extruder. The suspension was introduced through a side feeding device and mixed with the molten polymer to immediately devolatilize the water in the nano-suspension. Phenytoin nano-crystals were dispersed and embedded in the molten polymer. Investigation of the nano-extrudates via transmission electron microscopy and atomic force microscopy showed that the nano-crystals were embedded de-aggregated in the extrudates. Furthermore, no changes in the crystallinity (due to the mechanical and thermal stress) occurred. The dissolution studies confirmed that the prepared nano-extrudates increased the solubility of nano-crystalline phenytoin, regardless of the polymer. Our work demonstrates that NANEX represents a promising new platform technology in the design of novel drug delivery systems to improve drug performance.

Smoothed particle hydrodynamics (SPH) has become increasingly important during recent decades. Its meshless nature, inherent representation of convective transport and ability to simulate free surface flows make SPH particularly promising with regard to simulations of industrial mixing devices for high-viscous fluids, which often have complex rotating geometries and partially filled regions (e.g., twin-screw extruders). However, incorporating the required geometries remains a challenge in SPH since the most obvious and most common ways to model solid walls are based on particles (i.e., boundary particles and ghost particles), which leads to complications with arbitrarily-curved wall surfaces. To overcome this problem, we developed a systematic method for determining an adequate interaction between SPH particles and a continuous wall surface based on the underlying SPH equations. We tested our new approach by using the open-source particle simulator "LIGGGHTS" and comparing the velocity profiles to analytical solutions and SPH simulations with boundary particles. Finally, we followed the evolution of a tracer in a twin-cam mixer during the rotation, which was experimentally and numerically studied by several other authors, and ascertained good agreement with our results. This supports the validity of our newly-developed wall interaction method, which constitutes a step forward in SPH simulations of complex geometries. (C) 2014 Elsevier B.V. All rights reserved.

In this study, we present a one-dimensional (1D) model of the metering zone of a modular, co-rotating twin-screw extruder for pharmaceutical hot melt extrusion (HME). The model accounts for filling ratio, pressure, melt temperature in screw channels and gaps, driving power, torque and the residence time distribution (RTD). It requires two empirical parameters for each screw element to be determined experimentally or numerically using computational fluid dynamics (CFD). The required Nusselt correlation for the heat transfer to the barrel was determined from experimental data. We present results for a fluid with a constant viscosity in comparison to literature data obtained from CFD simulations. Moreover, we show how to incorporate the rheology of a typical, non-Newtonian polymer melt, and present results in comparison to measurements. For both cases, we achieved excellent agreement. Furthermore, we present results for the RTD, based on experimental data from the literature, and found good agreement with simulations, in which the entire HME process was approximated with the metering model, assuming a constant viscosity for the polymer melt.

Scale-up of nanoparticle batch productions continues to be a major challenge in the pharmaceutical nanotechnology. Continuously operating microreactors have great potential to circumvent the scale-up difficulties. In this work a passive microreactor was used for the first time for the electrostatic self-assembly of biodegradable, mucoadhesive thiomer-protamine nanoparticles for drug delivery. The influence of three different parameters (the overall flow rate, the educt mass ratio and the molecular weight of the thiomer) on the particle characteristics was tested for the microreactor production and compared to the results of a successful 1 ml-batch reaction. As the flow rate increased (2, 5, 9, 16 ml min(-1)), the particle sizes and the polydispersity indexes decreased. In addition, the protamine : 5 kDa thiomer binding ratio and hence the zeta potential, as a measure of the suspension's stability, increased to >+40 mV due to better mixing during the microreactor production at a flow rate of 16 ml min(-1). Producing nanoparticles from different mass ratios of 5 kDa thiomer : protamine (1 : 1, 1 : 3, 1 : 5) in the microreactor at this flow rate resulted in smaller particles with more distinct zeta potentials than those prepared by the 1 ml-batch reaction. Using a higher molecular weight thiomer (30 kDa) for the microreactor production at a flow rate of 16 ml min(-1) led to slightly increased mean particle sizes (125.0 nm) compared to those produced by the 1 ml-batch reaction (102.9 nm). However, there was still a decrease in the width of the particle size distributions. In addition to the experimental work, a numerical model based on the population balance equation was developed. The results presented in this paper are in agreement with the experimental findings, especially with regard to the trends of decreased particle size and polydispersity with the increasing flow rate. The model results confirm that mixing effects to a great extent determine the particle size distribution of the resulting nanoparticles and show that spatial inhomogeneity of the mixing process must be taken into account. The unprecedented use of a passive microreactor for the production of biodegradable thiomer-protamine nanoparticles by electrostatic self-assembly was a success. Due to the reactor's continuous way of operation, not only were the scale-up problems of batch reactions overcome, but particle characteristics were also improved because of a better mixing effect.

Drugs can be absorbed well in the oral cavity, which eliminates problems related to intestinal and hepatic first-pass metabolism. Although it is well-established that nanoparticles are small enough to penetrate/permeate epithelial barriers, there is no clear understanding of how they interact with the buccal mucosa. This work provides useful information regarding particle properties with regard to mucosal uptake and can be used for the rational design of nanocarriers. In the buccal mucosa, the uptake of neutral polystyrene nanoparticles (PP) is size-dependent. Compared to 25 and 50 nm particles, 200 nm PP particles penetrate into deeper regions of the mucosa. This is attributed to the structure of the buccal mucosa, i.e., mucus layer and microplicae. The particles permeate the mucus layer and deposit in ridge-like folds of superficial buccal cells. Thus, the effects of thermodynamic driving forces and/or interparticle electrostatic repulsion are enhanced and cellular uptake might be reduced for smaller particle sizes.