David Brancazio

Three-Dimensional Printing: The Physics and Implications of Additive Manufacturing

Abstract Three Dimensional Printing is a process for creating parts directly from a computer model. 3D Printing builds parts in layers by spreading a layer of powder and then selectively joining the powder in the layer by ink-jet printing of a binder material. After all layers are printed, the layer loose of powder is removed to reveal the finished part. Application areas include ceramic molds for metal castings, directly printed parts for end-use and for use as tooling, ceramic preforms for metal matrix composites, structural ceramic parts, and others. 3D Printing is a member of a group of layer manufacturing techniques which have the primary distinguishing feature of creating parts by the controlled addition (rather than subtraction) of material. The primitive building element in 3D Printing is a spherical ensemble of powder particles held together by one droplet of binder. Ballistic effects are important in the formation of primitives due to kinetic energy associated with the incoming droplet. Stitching together of droplets forms surfaces and hence determines surface finish. Vertical dimensional control is determined in pan by the compression of powder layers by subsequently applied powder. These physical mechanisms help to determine the dimensional control and surface finish of 3D Printed parts.

Integrated hot-melt extrusion – injection molding continuous tablet manufacturing platform: Effects of critical process parameters and formulation attributes on product robustness and dimensional stability

This study provides a framework for robust tablet development using an integrated hot-melt extrusion-injection molding (IM) continuous manufacturing platform. Griseofulvin, maltodextrin, xylitol and lactose were employed as drug, carrier, plasticizer and reinforcing agent respectively. A pre-blended drug-excipient mixture was fed from a loss-in-weight feeder to a twin-screw extruder. The extrudate was subsequently injected directly into the integrated IM unit and molded into tablets. Tablets were stored in different storage conditions up to 20 weeks to monitor physical stability and were evaluated by polarized light microscopy, DSC, SEM, XRD and dissolution analysis. Optimized injection pressure provided robust tablet formulations. Tablets manufactured at low and high injection pressures exhibited the flaws of sink marks and flashing respectively. Higher solidification temperature during IM process reduced the thermal induced residual stress and prevented chipping and cracking issues. Polarized light microscopy revealed a homogeneous dispersion of crystalline griseofulvin in an amorphous matrix. DSC underpinned the effect of high tablet residual moisture on maltodextrin-xylitol phase separation that resulted in dimensional instability. Tablets with low residual moisture demonstrated long term dimensional stability. This study serves as a model for IM tablet formulations for mechanistic understanding of critical process parameters and formulation attributes required for optimal product performance.

Tablet coating by injection molding technology – Optimization of coating formulation attributes and coating process parameters

Graphical abstract Figure. No Caption available. Abstract We developed and evaluated a solvent‐free injection molding (IM) coating technology that could be suitable for continuous manufacturing via incorporation with IM tableting. Coating formulations (coating polymers and plasticizers) were prepared using hot‐melt extrusion and screened via stress‐strain analysis employing a universal testing machine. Selected coating formulations were studied for their melt flow characteristics. Tablets were coated using a vertical injection molding unit. Process parameters like softening temperature, injection pressure, and cooling temperature played a very important role in IM coating processing. IM coating employing polyethylene oxide (PEO) based formulations required sufficient room humidity (>30% RH) to avoid immediate cracks, whereas other formulations were insensitive to the room humidity. Tested formulations based on Eudrajit E PO and Kollicoat IR had unsuitable mechanical properties. Three coating formulations based on hydroxypropyl pea starch, PEO 1,000,000 and Opadry had favorable mechanical (<700 MPa Young’s modulus, >35% elongation, >95 × 104 J/m3 toughness) and melt flow (>0.4 g/min) characteristics, that rendered acceptable IM coats. These three formulations increased the dissolution time by 10, 15 and 35 min, respectively (75% drug release), compared to the uncoated tablets (15 min). Coated tablets stored in several environmental conditions remained stable to cracking for the evaluated 8‐week time period.

Demonstration of pharmaceutical tablet coating process by injection molding technology

We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300 μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets.

A compact, portable, re-configurable, and automated system for on-demand pharmaceutical tablet manufacturing

Due to the complex nature of the pharmaceutical supply chain, the industry faces several major challenges when it comes to ensuring an adequate supply of quality drug products. These challenges are not only the causes of supply chain disruptions and financial loss, but can also prevent underserved and remote areas from receiving life-saving drugs. As a preliminary demonstration to mitigate all these challenges, at MIT we have developed active pharmaceutical ingredients manufacturing in a miniature platform. However, manufacturing of final oral solid dosage as tablets from drug substances had not been demonstrated. In this study, a compact, portable, re-configurable, and automated tablet manufacturing system, roughly the size of a North American household oven, [72.4 cm (length) × 53.3 cm (width) × 134.6 cm (height)] was designed, built and demonstrated. This miniature system is able to manufacture on-demand tablets from drug crystals on a scale of hundreds to thousands per day. Ibuprofen and Diazepam, each having different drug loading, were manufactured using this miniature system and meet U.S. Pharmacopeia standards. We foresee this flexible, miniature, plug-and-play pharmaceutical solids dosage manufacturing system advancing on-demand ready-to-use pharmaceuticals enabling future treatment of human diseases at the point-of-care.