Influence of particle size on flowability and printability in a pharmaceutical 3D printer

The demand for personalized medicine has continued to rise in recent years. One way of providing individual dosages is to use additive manufacturing technologies, such as 3D printing via direct powder extrusion1 with e.g. the 3D printer from the company FabRx (M3DIMAKER™). This is a novel, single-step printing process with the aim of producing printlets (3D printed tablets) directly from powdered materials2. In this process, a powder blend (e.g. polymers and active ingredients) is feed directly into a hopper, extruded and melted by a heating element. The resulting strand is deposited according to the previously designed geometry1. To ensure a good and reproducible process, the flowability of the powder is crucial and needs to be investigated. The European Pharmacopoeia lists four methods for testing powder flow: the angle of repose, the compressibility index or Hausner ratio, the flow rate through an orifice, and the shear cell. Unfortunately, none reflects the specific conditions encountered by a powder as it flows from a hopper into and through an extruder. The results obtained from the pharmacopoeial methods do not match the observations during 3D printing and are therefore not appropriate for testing powders regarding their suitability in the direct powder extrusion process. In the absence of appropriate pharmacopoeial methods, this work provides a method to determine the flowability in an extruder. For this purpose, a replica of the extruder of the 3D printer (FabRx's M3DIMAKER™) was built. To obtain particles of multiple size ranges, different polymers were extruded using a single screw extruder (Noztek Pro, Noztek), ground and sieved to obtain 6 fractions with similar particle characteristics (density, morphology, etc.). The selected 5 different polymers in this study were: Hypromellose acetate succinate, polyvinylalcohol, vinylpyrrolidone-vinyl acetate copolymer, polyvinyl alcohol-polyethylene glycol copolymer and basic butylated methacrylate copolymer. The resulting polymers and the original powder were filled into the replicas hopper and the motor was started. The time and power required to convey a certain amount of powder through the extruder were recorded. From this, the work required was calculated and quantified. The different values enabled to quantitatively describe the flow behavior in the extruder and assess the behavior in the 3D printer.