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

Hellen Windolf,Julian Quodbach,Rebecca Chamberlain,Arnaud Delmotte

doi:10.3390/pharmaceutics14020432

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.

Highlights

A global threat to healthcare is falsified and substandard medicine
The transfer of the blind-watermarking concept of Delmotte et al [53] was first tested with commercial polylactic acid filaments (PLA, Bavaria filaments, Freilassing, Germany)
It was shown that the blind-watermarking process can be used for oblong shaped tablets, as the bit-insertion and scanning process is currently only possible for straight, flat sides

Summary

Introduction

A global threat to healthcare is falsified and substandard medicine. An estimated 10% of medicines on the market are falsified [1,2,3,4,5,6,7,8]. The percentage of falsified and substandard drugs is higher, at about 10–30% [3,9,10,11,12,13,14,15,16]. At risk of counterfeiting are those drugs that are expensive or promise high sales. In developing countries, these are often antibiotics, viral drugs, or malaria preparations [14,15,16,17]. In rich countries, falsified medicines of new and expensive so-called “lifestyle pharmaceuticals”

Methods

Discussion

Conclusion