ABSTRACT
The potential for delayed evacuation of injured Service members from austere environments highlights the need to develop solutions that can stabilize a wound and enable mobility during these prolonged casualty care (PCC) scenarios. Lower extremity fractures have traditionally been treated by immobilization (splinting) followed by air evacuation - a paradigm not practical in PCC scenarios. In the civilian sector, treatment of extremity injuries sustained during remote recreational activities have similar challenges, particularly when adverse weather or terrain precludes early ground or air rescue. This review examines currently available fracture treatment solutions to include splinting, orthotic devices, and biological interventions and evaluates their feasibility: 1) for prolonged use in austere environments and 2) to enable patient mobilization. This review returned three common types of splints to include: a simple box splint, pneumatic splints, and traction splints. None of these splinting techniques allowed for ambulation. However, fixed facility-based orthotic interventions that include weight-bearing features may be combined with common splinting techniques to improve mobility. Biologically-focused technologies to stabilize a long bone fracture are still in their infancy. Integrating design features across these technologies could generate advanced treatments which would enable mobility, thus maximizing survivability until patient evacuation is feasible.
ABSTRACT
The objective of this study was to develop a novel closed-loop controlled continuous tablet manufacturing line, which first uses hot melt extrusion (HME) to produce pellets based on API and a polymer matrix. Such systems can be used to make complex pharmaceutical formulations, e.g., amorphous solid dispersions of poorly soluble APIs. The pellets are then fed to a direct compaction (DC) line blended with an external phase and tableted continuously. Fully-automated processing requires advanced control strategies, e.g., for reacting to raw material variations and process events. While many tools have been proposed for in-line process monitoring and real-time data acquisition, establishing real-time automated feedback control based on in-process control strategies remains a challenge. Control loops were implemented to assess the quality attributes of intermediates and product and to coordinate the mass flow rate between the unit operations. Feedback control for the blend concentration, strand temperature and pellet thickness was accomplished via proportional integral derivative (PID) controllers. The tablet press hopper level was controlled using a model predictive controller. To control the mass flow rates in all unit operations, several concepts were developed, with the tablet press, the extruder or none assigned to be the master unit of the line, and compared via the simulation.
