Three-dimensional printing (3DP) has demonstrated great potential for multi-material fabrication because of its capability for printing bespoke and spatially separated material conformations. Such a concept could revolutionise the pharmaceutical industry, enabling the production of personalised, multi-layered drug products on demand. Here, we developed a novel stereolithographic (SLA) 3D printing method that, for the first time, can be used to fabricate multi-layer constructs (polypills) with variable drug content and/or shape. Using this technique, six drugs, including paracetamol, caffeine, naproxen, chloramphenicol, prednisolone and aspirin, were printed with different geometries and material compositions. Drug distribution was visualised using Raman microscopy, which showed that whilst separate layers were successfully printed, several of the drugs diffused across the layers depending on their amorphous or crystalline phase. The printed constructs demonstrated excellent physical properties and the different material inclusions enabled distinct drug release profiles of the six actives within dissolution tests. For the first time, this paper demonstrates the feasibility of SLA printing as an innovative platform for multi-drug therapy production, facilitating a new era of personalised polypills.

Three-dimensional printing (3DP) has the potential to cause a paradigm shift in the manufacture of pharmaceuticals, enabling personalised medicines to be produced on-demand. To facilitate integration into healthcare, non-destructive characterisation techniques are required to ensure final product quality. Here, the use of process analytical technologies (PAT), including near infrared spectroscopy (NIR) and Raman confocal microscopy, were evaluated on paracetamol-loaded 3D printed cylindrical tablets composed of an acrylic polymer (Eudragit L100-55). Using a portable NIR spectrometer, a calibration model was developed, which predicted successfully drug concentration across the range of 4-40% w/w. The model demonstrated excellent linearity (R2 = 0.996) and accuracy (RMSEP = 0.63%) and results were confirmed with conventional HPLC analysis. The model maintained high accuracy for tablets of a different geometry (torus shapes), a different formulation type (oral films) and when the polymer was changed from acrylic to cellulosic (hypromellose, HPMC). Raman confocal microscopy showed a homogenous drug distribution, with paracetamol predominantly present in the amorphous form as a solid dispersion. Overall, this article is the first to report the use of a rapid 'point-and-shoot' approach as a non-destructive quality control method, supporting the integration of 3DP for medicine production into clinical practice.

Mass loss at specified temperatures has been used widely to determine amounts of organic matter and carbonate in sediment samples. The loss on ignition (LOI) method is cheap and simple, but is time-consuming and provides information only for specific, pre-determined temperatures. It also requires relatively large sample sizes and is destructive. Thermogravimetric analysis (TGA) is an alternative method for determination of organic and carbonate content in sediment samples, and provides accurate and precise data in a time-efficient manner. We compared results from these two thermal analysis techniques, which were applied to sediment samples from a submerged landscape (Doggerland). An organic-rich peat sample and a silty fine-sand sample were used. An unpaired t-test was used to test agreement and repeatability of the two analytical techniques. One advantage of being able to monitor mass loss throughout the analytical operation is that free and bound moisture losses can be distinguished. TGA is less time-consuming, involves automated sample handling (minimising operator error), and can yield reliable data from sample masses (typically 30–50 mg), which are much smaller than those needed for LOI (typically 3–5 g). The unpaired t-test, along with precision and repeatability analyses led us to conclude that TGA can be used instead of LOI to provide reliable measures of organic matter and carbonate content in sediments, and has several advantages over LOI.

A unique approach is applied in preparing the first ‘air-stable’ formulation of form III of paracetamol, long regarded as a highly unstable form.