PET/CT imaging of 3D printed devices in the gastrointestinal tract of rodents

Fused deposition modelling (FDM) 3D printing (3DP) is a revolutionary technology with the potential to transform drug product design in both the pre-clinical and clinical arena. The objective of this pilot study was to explore the intestinal behaviour of four different polymer-based devices fabricated using FDM 3DP technology in rats. Small capsular devices of 8.6 mm in length and 2.65 mm in diameter were printed from polyvinyl alcohol-polyethylene glycol graft-copolymer (PVA-PEG copolymer, Kollicoat IR), hydroxypropylcellulose (HPC, Klucel), ethylcellulose (EC, Aqualon N7) and hypromellose acetate succinate (HPMCAS, Aquasolve-LG). A smaller sized device, 3.2 mm in length and 2.65 mm in diameter, was also prepared with HPMCAS to evaluate the cut off size of gastric emptying of solid formulations in rats. The devices were radiolabelled with Fluorodeoxyglucose (18F-FDG) and small animal positron emission tomography/computed tomography (microPET/CT) was used to track the movement and disintegration of the fabricated devices in the rats. The PVA-PEG copolymer and HPC devices disintegrated after 60min following oral administration. The EC structures did not disintegrate in the gastrointestinal tracts of the rats, whereas the HPMCAS-based systems disintegrated after 420 min. Interestingly, it was noted that the devices which remained intact over the course of the study had not emptied from the stomach of the rats. This was also the case with the smaller sized device. In summary, we report for the first time, the use of a microPET/CT imaging technique to evaluate the in vivo behaviour of 3D printed formulations. The manipulation of the 3D printed device design could be used to fabricate dosage forms of varying sizes and geometries with better gastric emptying characteristics suitable for rodent administration. The increased understanding of the capabilities of 3DP in dosage form design could, henceforth, accelerate pre-clinical testing of new drug candidates in animal models

Incidental exposure and L3 learning of morphosyntax

Evidence of learning following incidental exposure has been found for aspects of nonnative syntax in adults (Rebuschat & Williams, 2006, 2012; Williams & Kuribara, 2008). However, little research has tested delayed effects of learning under an incidental condition or moved beyond word order. This study investigated learning of third language (L3) morphosyntax (word order and case marking) under an incidental exposure condition. Participants were second language Spanish learners exposed auditorily to a semiartificial language, Japlish, during a semantic plausibility judgment task. Performance following exposure to L3 Japlish was assessed with acceptability judgment and picture-matching tasks that were administered immediately after exposure and 2 weeks later. Results on immediate tests showed a significant learning effect on acceptability judgment but none for picture matching. At delayed testing, results showed maintenance of the learning effect on acceptability judgment and significantly improved performance on picture matching. Results additionally showed that many of the learners arrived at the correct Japlish word-order rule; fewer did so for case marking. Follow-up analyses indicated that this rule knowledge, as measured by debriefing information, was important for performance on both assessment tasks, particularly at delayed testing. The results suggest that learning of L3 structures can take place following incidental exposure, that such learning is durable and undergoes improvement, and that development of reportable rule knowledge may also play an important role