Blind-Watermarking—Proof-of-Concept of a Novel Approach to Ensure Batch Traceability for 3D Printed Tablets

Abstract

Falsified medicines are a major issue and a threat around the world. Various approaches are currently being investigated to mitigate the threat. In this study, a concept is tested that encodes binary digits (bits) on the surface of Fused Deposition Modelling (FDM) 3D printed geometries. All that is needed is a computer, a FDM 3D printer and a paper scanner for detection. For the experiments, eleven different formulations were tested, covering the most used polymers for 3D printing in pharma: Ethylene-vinyl acetate (EVA), polyvinyl alcohol (PVA), polylactic acid (PLA), Hypromellose (HPMC), ethyl cellulose (EC), basic butylated-methacrylate-copolymer (EPO), and ammonio-methacrylate-copolymer type A (ERL). In addition, the scanning process and printing process were evaluated. It was possible to print up to 32 bits per side on oblong shaped tablets corresponding to the dimensions of market preparations of oblong tablets and capsules. Not all polymers or polymer blends were suitable for this method. Only PVA, PLA, EC, EC+HPMC, and EPO allowed the detection of bits with the scanner. EVA and ERL had too much surface roughness, too low viscosity, and cooled down too slowly preventing the detection of bits. It was observed that the addition of a colorant or active pharmaceutical ingredient (API) could facilitate the detection process. Thus, the process could be transferred for 3D printed pharmaceuticals, but further improvement is necessary to increase robustness and allow use for more materials.

Polyvinyl Alcohol, a Versatile Excipient for Pharmaceutical 3D Printing

“…An API addition was also helpful in the detection process. This notion was presented as ground-breaking, providing a solution for traceability concerns associated with 3D-printed dosage forms [ 16 ].…”

“…In addition, because they are so simple to deliver, healthcare personnel are typically not needed [ 3 ]. A significant number of studies have focused on inspecting PVA’s printability when combined with different types of drugs, on analyzing the stability of the printed forms, or on many other aspects, like the geometry of the printlets, multidrug-containing dosage forms, disease-specific tablets, and batch traceability [ 12 , 13 , 14 , 15 , 16 ]. The purpose of this review was to evaluate the developments regarding the use of PVA in hot melt extrusion (HME) coupled with FDM to print solid oral dosage forms containing one or more active pharmaceutical ingredients (APIs).…”

Study and Characterization of Polyvinyl Alcohol-Based Formulations for 3D Printlets Obtained via Fused Deposition Modeling

“…There have been successful attempts to extrude partially hydrolyzed grades by adding hydrophilic plasticizers containing hydroxyl groups, such as glycerin [ 20 ] and sorbitol [ 19 ], which form hydrogen bonds with the PVA molecule and lower its Tg. Such experiments have also been conducted focusing on the production of strands for FDM 3D printing for pharmaceutical applications [ 14 , 21 , 22 , 23 , 24 ].…”

Thermal degradation of Affinisol HPMC: Optimum Processing Temperatures for Hot Melt Extrusion and 3D Printing

“…Nowadays, Affinisol is commonly attempted to be used at temperatures close to 200°C, either due to the high melting temperatures (T m ) of the mixed-in drugs or other excipients or due to the consequent processing of the HME-prepared extrudate [ 15 , 17 , 23 ]. The latter is particularly relevant with the recent boom of the 3D-printing technique usage [ 41 – 45 ] in the field of pharmacy. Since the acceptable adhesion of the 3D-printed layers is achieved at relatively high temperatures (usually close to 190–200°C for Affinisol) [ 23 ], the thermal degradation of Affinisol has recently emerged as a pressing issue.…”