Can filaments be stored as a shelf-item for on-demand manufacturing of oral 3D printed tablets? An initial stability assessment

3D printing of oral solid dosage forms is a recently introduced approach for dose personalisation. Fused deposition modelling (FDM) is one of the promising and heavily researched 3D printing techniques in the pharmaceutical field. However, the successful application of this technique relies greatly on the mass manufacturing of physically and chemically stable filaments, that can be readily available as a shelf item to be 3D printed on-demand. In this work, the stability of methacrylate polymers (Eudragit EPO, RL, L100-55 and S100), hydroxypropyl cellulose (HPC SSL) and polyvinyl pyrrolidone (PVP)-based filaments over 6 months were investigated. Filaments manufactured by hot melt extrusion (HME) were stored at either 5 °C or 30 °C + 65 %RH with/without vacuuming. The effects of storage on their dimensions, visual appearance, thermal properties, and ‘printability’ were analysed. Theophylline content, as well as in vitro release from the 3D printed tablets were also investigated. The filaments were analysed before storage, then after 1, 3 and 6 months from the manufacturing date. Storing the filaments at these conditions had a significant effect on their physical properties, such as shape, dimensions, flexibility and hence compatibility with FDM 3D printing. In general, the methacrylate-based filaments were more physically stable and compatible with FDM 3D printing following storage. Owing to their hygroscopic nature, cellulose- and PVP-based filaments demonstrated a reduction in their glass transition temperature upon storage, leading to increased flexibility and incompatibility with FDM 3D printer. Theophylline contents was not significantly changed during the storage. This work provides preliminary data for the impact of polymer species on the long-term stability of filaments. In general, storage and packaging conditions have a major impact on the potential of on-demand manufacturing of 3D printed tablets using hot melt extruded filaments

The relationship between water, sanitation and schistosomiasis : a systematic review and meta-analysis

BACKGROUND: Access to "safe" water and "adequate" sanitation are emphasized as important measures for schistosomiasis control. Indeed, the schistosomes' lifecycles suggest that their transmission may be reduced through safe water and adequate sanitation. However, the evidence has not previously been compiled in a systematic review. METHODOLOGY: We carried out a systematic review and meta-analysis of studies reporting schistosome infection rates in people who do or do not have access to safe water and adequate sanitation. PubMed, Web of Science, Embase, and the Cochrane Library were searched from inception to 31 December 2013, without restrictions on year of publication or language. Studies' titles and abstracts were screened by two independent assessors. Papers deemed of interest were read in full and appropriate studies included in the meta-analysis. Publication bias was assessed through the visual inspection of funnel plots and through Egger's test. Heterogeneity of datasets within the meta-analysis was quantified using Higgins' I2. PRINCIPAL FINDINGS: Safe water supplies were associated with significantly lower odds of schistosomiasis (odds ratio (OR) = 0.53, 95% confidence interval (CI): 0.47-0.61). Adequate sanitation was associated with lower odds of Schistosoma mansoni, (OR = 0.59, 95% CI: 0.47-0.73) and Schistosoma haematobium (OR = 0.69, 95% CI: 0.57-0.84). Included studies were mainly cross-sectional and quality was largely poor. CONCLUSIONS/SIGNIFICANCE: Our systematic review and meta-analysis suggests that increasing access to safe water and adequate sanitation are important measures to reduce the odds of schistosome infection. However, most of the studies were observational and quality was poor. Hence, there is a pressing need for adequately powered cluster randomized trials comparing schistosome infection risk with access to safe water and adequate sanitation, more studies which rigorously define water and sanitation, and new research on the relationships between water, sanitation, hygiene, human behavior, and schistosome transmissio